TY - JOUR AU - Steunebrink, L.M. AU - Vonkeman, H.E. AU - Klooster, P.M. ten AU - Hoekstra, M. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der PY - 2016 UR - http://hdl.handle.net/2066/171347 AB - Despite considerable evidence on the efficacy and safety of early aggressive treat-to-target (T2T) strategies in early rheumatoid arthritis (RA), a proportion of patients still fail to reach remission. The goal of this study is to examine remission rates and predictors of remission in a real life T2T cohort of consecutive patients with a recent diagnosis of RA. Baseline demographics, clinical, laboratory and patient-reported variables and 1-year follow-up disease activity data were used from patients with early RA included in the DREAM remission induction cohort II study. Survival analyses and simple and multivariable logistic regression analyses were used to examine remission rates and significant predictors of achieving remission. A total of 137 recently diagnosed consecutive RA patients were available for this study. During the first year after inclusion, DAS28 remission was achieved at least once in 77.2 % of the patients and the median time to first remission was 17 weeks. None of the examined baseline variables were robustly associated with achieving remission within 1 year and in the multivariable analysis only lower ESR (p = 0.005) remained significantly associated with achieving fast remission within 17 weeks. During the first year of their disease a high proportion of recently diagnosed RA patient achieved remission, with only a small percentage of patients needing bDMARD therapy. Combined with the absence of baseline predictors of remission, this suggests that clinicians in daily clinical practice may focus on DAS28 scores only, without needing to take other patients characteristics into account. TI - Recently diagnosed rheumatoid arthritis patients benefit from a treat-to-target strategy: results from the DREAM registry EP - 615 SN - 0770-3198 IS - iss. 3 SP - 609 JF - Clinical Rheumatology VL - vol. 35 DO - https://doi.org/10.1007/s10067-016-3191-3 ER - TY - JOUR AU - Steunebrink, L.M. AU - Versteeg, G.A. AU - Vonkeman, H.E. AU - Klooster, P.M. ten AU - Kuper, H.H. AU - Zijlstra, T.R. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der PY - 2016 UR - http://hdl.handle.net/2066/172822 AB - BACKGROUND: Treat to target (T2T) is widely accepted as the standard of care for patients with rheumatoid arthritis (RA) and has been shown to be more effective than traditional routine care. The objective of this study was to compare the effectiveness of two T2T strategies in patients with early RA: a step-up approach starting with methotrexate (MTX) monotherapy (cohort I) versus an initial disease-modifying antirheumatic drug combination approach (cohort II). METHODS: A total of 128 patients from cohort II were case-control-matched with 128 patients from cohort I on gender, age, and baseline disease activity. Twelve-month follow-up data were available for 121 patients in both cohorts. The primary outcome was the proportion of patients having reached at least one 28-joint Disease Activity Score (DAS28) score <2.6 (remission) during 12 months of follow-up. Secondary outcomes were time until remission was achieved and mean DAS28 scores at 6- and 12-month follow-up. RESULTS: After 12 months of follow-up, remission was reached at least once in 77.3 % of the patients in cohort II versus 71.9 % in cohort I (P = 0.31). Median time until first remission was 17 weeks in cohort II versus 27 weeks in cohort I (P = 0.04). A significant time by strategy interaction was found in mean DAS28 scores. Post hoc analysis revealed a significant difference in mean DAS28 scores between both cohorts at 6 months (P = 0.04), but not at 12 months (P = 0.36). CONCLUSIONS: The initial combination strategy resulted in a comparable remission rate after 1 year but a significantly shorter time until remission. At 6 months, mean DAS28 scores were lower in patients with initial combination treatment than in those with step-up therapy. At 12 months, no significant differences remained in mean DAS28 scores or the proportion of patients in remission. TI - Initial combination therapy versus step-up therapy in treatment to the target of remission in daily clinical practice in early rheumatoid arthritis patients: results from the DREAM registry SN - 1478-6354 IS - iss. 1 SP - 60 JF - Arthritis Research & Therapy VL - vol. 18 DO - https://doi.org/10.1186/s13075-016-0962-9 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/172822/172822.pdf?sequence=1 ER - TY - JOUR AU - Moghadam, M. Ghiti AU - Vonkeman, H.E. AU - Klooster, P.M. ten AU - Tekstra, J. AU - Schaardenburg, D. van AU - Starmans-Kool, M. AU - Brouwer, E. AU - Bos, R. van den AU - Lems, W.F. AU - Colin, E.M. AU - Allaart, C.F. AU - Meek, I.L. AU - Landewe, R. AU - Moens, H.J. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der AU - Jansen, T.L.Th.A. PY - 2016 UR - http://hdl.handle.net/2066/171544 AB - OBJECTIVE: Tumor necrosis factor inhibitor (TNFi) biologic agents are an effective treatment for rheumatoid arthritis (RA). It is unclear whether patients whose disease is in remission or who have stable low disease activity need to continue use of TNFi or can stop this treatment. This study was undertaken to assess whether patients with established RA who are in remission or have stable low disease activity can effectively and safely stop their TNFi therapy. METHODS: The study was designed as a pragmatic multicenter, open-label randomized controlled trial. Inclusion criteria were a diagnosis of RA according to the American College of Rheumatology 1987 classification criteria, as well as use of a TNFi for at least 1 year along with a stable dose of disease-modifying antirheumatic drugs and a Disease Activity Score in 28 joints (DAS28) of <3.2 over the 6 months preceding trial inclusion. Patients were randomized in a 2:1 ratio to either stop or continue treatment with their current TNFi. Flare was defined as a DAS28 of >/=3.2 during the 12-month follow-up period and an increase in score of >/=0.6 compared to the baseline DAS28. RESULTS: In total, 531 patients were allocated to the stop group and 286 to the TNFi continuation group. At 12 months, more patients had experienced a flare in the stop group (272 [51.2%] of 531) than in the continuation group (52 [18.2%] of 286; P < 0.001). The hazard ratio for occurrence of a flare after stopping TNFi was 3.50 (95% confidence interval [95% CI] 2.60-4.72). The mean DAS28 in the stop group was significantly higher during the follow-up period compared to that in the continuation group (P < 0.001). Of the 195 patients who restarted TNFi treatment after experiencing a flare and within 26 weeks after stopping, 165 (84.6%) had regained a DAS28 of <3.2 by 6 months later, and the median time to a regained DAS28 of <3.2 was 12 weeks (95% Cl 10.7-13.3). There were more hospitalizations in the stop group than in the continuation group (6.4% versus 2.4%). CONCLUSION: Stopping TNFi treatment results in substantially more flares than does continuation of TNFi in patients with established RA in remission or with stable low disease activity. TI - Stopping Tumor Necrosis Factor Inhibitor Treatment in Patients With Established Rheumatoid Arthritis in Remission or With Stable Low Disease Activity: A Pragmatic Multicenter, Open-Label Randomized Controlled Trial EP - 1817 SN - 2326-5191 IS - iss. 8 SP - 1810 JF - Arthritis & Rheumatology VL - vol. 68 DO - https://doi.org/10.1002/art.39626 ER - TY - JOUR AU - Oude Voshaar, M.A.H. AU - Klooster, P.M. ten AU - Bode, C. AU - Vonkeman, H.E. AU - Glas, C.A. AU - Jansen, T.L.Th.A. AU - Albada-Kuipers, I. van AU - Riel, P.L.C.M. van AU - Laar, M.A. van der PY - 2015 UR - http://hdl.handle.net/2066/154577 AB - OBJECTIVE: To compare the psychometric functioning of multidimensional disease-specific, multiitem generic, and single-item measures of fatigue in patients with rheumatoid arthritis (RA). METHODS: Confirmatory factor analysis (CFA) and longitudinal item response theory (IRT) modeling were used to evaluate the measurement structure and local reliability of the Bristol RA Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ), the Medical Outcomes Study Short Form-36 (SF-36) vitality scale, and the BRAF Numerical Rating Scales (BRAF-NRS) in a sample of 588 patients with RA. RESULTS: A 1-factor CFA model yielded a similar fit to a 5-factor model with subscale-specific dimensions, and the items from the different instruments adequately fit the IRT model, suggesting essential unidimensionality in measurement. The SF-36 vitality scale outperformed the BRAF-MDQ at lower levels of fatigue, but was less precise at moderate to higher levels of fatigue. At these levels of fatigue, the living, cognition, and emotion subscales of the BRAF-MDQ provide additional precision. The BRAF-NRS showed a limited measurement range with its highest precision centered on average levels of fatigue. CONCLUSION: The different instruments appear to access a common underlying domain of fatigue severity, but differ considerably in their measurement precision along the continuum. The SF-36 vitality scale can be used to measure fatigue severity in samples with relatively mild fatigue. For samples expected to have higher levels of fatigue, the multidimensional BRAF-MDQ appears to be a better choice. The BRAF-NRS are not recommended if precise assessment is required, for instance in longitudinal settings. TI - Assessment of Fatigue in Rheumatoid Arthritis: A Psychometric Comparison of Single-item, Multiitem, and Multidimensional Measures EP - 420 SN - 0315-162X IS - iss. 3 SP - 413 JF - The Journal of Rheumatology VL - vol. 42 DO - https://doi.org/10.3899/jrheum.140389 ER - TY - JOUR AU - Kearsley-Fleet, L. AU - Zavada, J. AU - Hetland, M.L. AU - Nordstrom, D.C. AU - Aaltonen, K.J. AU - Listing, J. AU - Zink, A. AU - Gati, T. AU - Rojkovich, B. AU - Iannone, F. AU - Gremese, E. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der AU - Lie, E. AU - Kvien, T.K. AU - Canhao, H. AU - Fonseca, J.E. AU - Rotar, Z. AU - Loza, E. AU - Carmona, L. AU - Askling, J. AU - Johansson, K. AU - Finckh, A. AU - Dixon, W.G. AU - Hyrich, K.L. PY - 2015 UR - http://hdl.handle.net/2066/154113 AB - OBJECTIVE: Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. METHODS: Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. RESULTS: A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers` collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. CONCLUSION: In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across registers. TI - The EULAR Study Group for Registers and Observational Drug Studies: comparability of the patient case mix in the European biologic disease modifying anti-rheumatic drug registers EP - 1079 SN - 1462-0324 IS - iss. 6 SP - 1074 JF - Rheumatology VL - vol. 54 DO - https://doi.org/10.1093/rheumatology/keu446 ER - TY - JOUR AU - Manders, S.H.M. AU - Kievit, W. AU - Adang, E.M. AU - Brus, H.L. AU - Moens, H.J. AU - Hartkamp, A. AU - Hendriks, L AU - Brouwer, E. AU - Visser, H. AU - Vonkeman, H.E. AU - Hendrikx, J. AU - Jansen, T.L. AU - Westhovens, R. AU - Laar, M.A. van der AU - Riel, P.L.C.M. van PY - 2015 UR - http://hdl.handle.net/2066/154892 AB - INTRODUCTION: For patients with rheumatoid arthritis (RA) whose treatment with a tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment options are available. Often, another TNFi or a biological with another mode of action is prescribed. The objective of this study was to compare the effectiveness and cost-effectiveness of three biologic treatments with different modes of action in patients with RA whose TNFi therapy is failing. METHODS: We conducted a pragmatic, 1-year randomised trial in a multicentre setting. Patients with active RA despite previous TNFi treatment were randomised to receive abatacept, rituximab or a different TNFi. The primary outcome (Disease Activity Score in 28 joints) and the secondary outcomes (Health Assessment Questionnaire Disability Index and 36-item Short Form Health Survey scores) were analysed using linear mixed models. Cost-effectiveness was analysed on the basis of incremental net monetary benefit, which was based on quality-adjusted life-years (calculated using EQ-5D scores), and all medication expenditures consumed in 1 year. All analyses were also corrected for possible confounders. RESULTS: Of 144 randomised patients, 5 were excluded and 139 started taking abatacept (43 patients), rituximab (46 patients) or a different TNFi (50 patients). There were no significant differences between the three groups with respect to multiple measures of RA outcomes. However, our analysis revealed that rituximab therapy is significantly more cost-effective than both abatacept and TNFi over a willingness-to-pay range of 0 to 80,000 euros. CONCLUSIONS: All three treatment options were similarly effective; however, when costs were factored into the treatment decision, rituximab was the best option available to patients whose first TNFi treatment failed. However, generalization of these costs to other countries should be undertaken carefully. TRIAL REGISTRATION: Netherlands Trial Register number NTR1605 . Registered 24 December 2008. TI - Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre randomised trial SN - 1478-6354 SP - 134 JF - Arthritis Research & Therapy VL - vol. 17 DO - https://doi.org/10.1186/s13075-015-0630-5 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/154892/154892.pdf?sequence=1 ER - TY - JOUR AU - Manders, S.H.M. AU - Kievit, W. AU - Adang, E.M. AU - Jansen, T.J.G. AU - Stolk, J.N. AU - Visser, H. AU - Schilder, A.M. AU - Vonkeman, H.E. AU - Laar, M.A. van der AU - Riel, P.L.C.M. van PY - 2015 UR - http://hdl.handle.net/2066/155132 TI - Effectiveness of TNF inhibitor treatment with various methotrexate doses in patients with rheumatoid arthritis: results from clinical practice SN - 0003-4967 IS - iss. 3 SP - e24 JF - Annals of the Rheumatic Diseases VL - vol. 74 DO - https://doi.org/10.1136/annrheumdis-2014-207005 ER - TY - JOUR AU - Nikolaus, S. AU - Bode, C. AU - Taal, E. AU - Vonkeman, H.E. AU - Glas, C.A. AU - Laar, M.A. van der PY - 2015 UR - http://hdl.handle.net/2066/154470 TI - Working mechanism of a multidimensional computerized adaptive test for fatigue in rheumatoid arthritis EP - 23 SN - 1477-7525 IS - iss. 1 SP - 23 JF - Health and Quality of Life Outcomes VL - vol. 13 DO - https://doi.org/10.1186/s12955-015-0215-7 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/154470/154470.pdf?sequence=1 ER - TY - JOUR AU - Manders, S.H.M. AU - Laar, M.A. van der AU - Rongen-van Dartel, S. AU - Bos, R. van den AU - Visser, H. AU - Brus, H.L. AU - Jansen, T. AU - Vonkeman, H.E. AU - Riel, P.L.C.M. van AU - Kievit, W. PY - 2015 UR - http://hdl.handle.net/2066/152779 AB - OBJECTIVES: To study the number of patients that taper or discontinue concomitant methotrexate (MTX) in daily practice in patients with rheumatoid arthritis (RA) treated with tumour necrosis factor inhibitor (TNFi) and to analyse the effects of that adaption on disease activity and drug survival. METHODS: Data were collected from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. Patients who started their first TNFi were included in the study. Treatment effectiveness after MTX tapering or discontinuation was analysed using Disease Activity Score of 28 joints (DAS28). Drug survival of the TNFi was analysed using the Cox proportional hazard model with a time-dependent covariate. RESULTS: In 458 patients (34%), MTX was tapered, 126 patients (10%) discontinued MTX and 747 patients (56%) continued MTX at the same dose. On average, DAS28 improved after tapering MTX (-0.40, -0.45) and after stopping MTX (-0.28, -0.12) at 6 and 12 months. In the taper group, 21% of the patients relapsed (DAS28 increase >0.6), and in the discontinuation group this was 21% and 24% at 6 and 12 months, respectively. Patients who taper and discontinue MTX have a similar DAS28 score over time as patients who continue MTX. Moreover, there was no influence of tapering or discontinuation of MTX on long-term drug survival of TNFi. CONCLUSIONS: In daily practice, tapering or discontinuation of concomitant MTX in patients with RA treated with TNFi frequently occurs and it does not seem to influence the average DAS28 over time or the long-term TNFi drug survival. It appears that in daily clinical practice the correct patients are selected to taper or discontinue MTX. TI - Tapering and discontinuation of methotrexate in patients with RA treated with TNF inhibitors: data from the DREAM registry SN - 2056-5933 IS - iss. 1 SP - e000147 JF - Rheumatic & Musculoskeletal Diseases Open VL - vol. 1 DO - https://doi.org/10.1136/rmdopen-2015-000147 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/152779/152779.pdf?sequence=1 ER - TY - JOUR AU - Voshaar, M.A. AU - Klooster, P.M. ten AU - Glas, C.A. AU - Vonkeman, H.E. AU - Taal, E. AU - Krishnan, E. AU - Moens, H.J. AU - Boers, M. AU - Terwee, C.B. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der PY - 2015 UR - http://hdl.handle.net/2066/152917 AB - OBJECTIVE: To evaluate the content validity and measurement properties of the Patient-Reported Outcome Measurement Information System (PROMIS) physical function item bank and a 20-item short form in patients with RA in comparison with the HAQ disability index (HAQ-DI) and 36-item Short Form Health Survey (SF-36) physical functioning scale (PF-10). METHODS: The content validity of the instruments was evaluated by linking their items to the International Classification of Functioning, Disability and Health (ICF) core set for RA. The measures were administered to 690 RA patients enrolled in the Dutch Rheumatoid Arthritis Monitoring registry. Measurement precision was evaluated using item response theory methods and construct validity was evaluated by correlating physical function scores with other clinical and patient-reported outcome measures. RESULTS: All 207 health concepts identified in the physical function measures referred to activities that are featured in the ICF. Twenty-three of 26 ICF RA core set domains are featured in the full PROMIS physical function item bank compared with 13 and 8 for the HAQ-DI and PF-10, respectively. As hypothesized, all three physical function instruments were highly intercorrelated (r 0.74-0.84), moderately correlated with disease activity measures (r 0.44-0.63) and weakly correlated with age (rs 0.07-0.14). Item response theory-based analysis revealed that a 20-item PROMIS physical function short form covered a wider range of physical function levels than the HAQ-DI or PF-10. CONCLUSION: The PROMIS physical function item bank demonstrated excellent measurement properties in RA. A content-driven 20-item short form may be a useful tool for assessing physical function in RA. TI - Validity and measurement precision of the PROMIS physical function item bank and a content validity-driven 20-item short form in rheumatoid arthritis compared with traditional measures EP - 2229 SN - 1462-0324 IS - iss. 12 SP - 2221 JF - Rheumatology VL - vol. 54 DO - https://doi.org/10.1093/rheumatology/kev265 ER - TY - JOUR AU - Umicevic-Mirkov, M. AU - Janss, L. AU - Vermeulen, S.H. AU - Laar, M.A. van der AU - Riel, P.L.C.M. van AU - Guchelaar (LUMC), H.J. AU - Brunner, H.G. AU - Albers, C.A. AU - Coenen, M.J.H. PY - 2015 UR - http://hdl.handle.net/2066/152200 AB - OBJECTIVES: Pharmacogenetic studies of tumour necrosis factor inhibitors (TNFi) response in patients with rheumatoid arthritis (RA) have largely relied on the changes in complex disease scores, such as disease activity score 28 (DAS28), as a measure of treatment response. It is expected that genetic architecture of such complex score is heterogeneous and not very suitable for pharmacogenetic studies. We aimed to select the most optimal phenotype for TNFi response using heritability estimates. METHODS: Using two linear mixed-modelling approaches (Bayz and GCTA), we estimated heritability, together with genomic and environmental correlations for the TNFi drug-response phenotype DeltaDAS28 and its separate components: Delta swollen joint count (SJC), Delta tender joint count (TJC), Delta erythrocyte sedimentation rate (ESR) and Delta visual-analogue scale of general health (VAS-GH). For this, we used genome-wide single nucleotide polymorphism (SNP) data from 878 TNFi-treated Dutch patients with RA. Furthermore, a multivariate genome-wide association study (GWAS) approach was implemented, analysing separate DAS28 components simultaneously. RESULTS: The highest heritability estimates were found for DeltaSJC ([Formula: see text]=0.76 and [Formula: see text]=0.87) and DeltaTJC ([Formula: see text]=0.62 and [Formula: see text]=0.82); lower heritability was found for DeltaDAS28 ([Formula: see text]=0.59 and [Formula: see text]=0.71) while estimates for DeltaESR and DeltaVASGH were near or equal to zero. The highest genomic correlations were observed for DeltaSJC and DeltaTJC (0.49), and the highest environmental correlation was seen between DeltaTJC and DeltaVASGH (0.62). The multivariate GWAS did not generate excess of low p values as compared with a univariate analysis of DeltaDAS28. CONCLUSIONS: Our results indicate that multiple SNPs together explain a substantial portion of the variation in change in joint counts in TNFi-treated patients with RA. In conclusion, of the outcomes studied, the joint counts are most suitable for TNFi pharmacogenetics in RA. TI - Estimation of heritability of different outcomes for genetic studies of TNFi response in patients with rheumatoid arthritis EP - 2187 SN - 0003-4967 IS - iss. 12 SP - 2183 JF - Annals of the Rheumatic Diseases VL - vol. 74 DO - https://doi.org/10.1136/annrheumdis-2014-205541 ER - TY - JOUR AU - Tran-Duy, A. AU - Boonen, A. AU - Kievit, W. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der AU - Severens, J.L. PY - 2014 UR - http://hdl.handle.net/2066/137456 AB - BACKGROUND: Management of rheumatoid arthritis (RA) is characterised by a sequence of disease-modifying antirheumatic drugs (DMARDs) and biological response modifiers (BRMs). In most of the Western countries, the drug sequences are determined based on disease activity and treatment history of the patients. A model for realistic patient outcomes should reflect the treatment pathways relevant for patients with specific characteristics. OBJECTIVE: This study aimed at developing a model that could simulate long-term patient outcomes and cost effectiveness of treatment strategies with and without inclusion of BRMs following a clinical guideline for treatment decisions. METHODS: Discrete event simulation taking into account patient characteristics and treatment history was used for model development. Treatment effect on disease activity, costs, health utilities and times to events were estimated using Dutch observational studies. Long-term progression of physical functioning was quantified using a linear mixed-effects model. Costs and health utilities were estimated using two-part models. The treatment strategy recommended by the Dutch Society for Rheumatology where both DMARDs and BRMs were available (Strategy 2) was compared with the treatment strategy without BRMs (Strategy 1). Ten thousand theoretical patients were tracked individually until death. In the probabilistic sensitivity analysis, Monte Carlo simulations were performed with 1,000 sets of parameters sampled from appropriate probability distributions. RESULTS: The simulated changes over time in disease activity and physical functioning were plausible. The incremental cost per quality-adjusted life-year gained of Strategy 2 compared with Strategy 1 was 124,011. At a willingness-to-pay threshold higher than 119,167, Strategy 2 dominated Strategy 1 in terms of cost effectiveness but the probability that the Strategy 2 is cost effective never exceeded 0.87. CONCLUSIONS: It is possible to model the outcomes of complex treatment strategies based on a clinical guideline for the management of RA. Following the Dutch guideline and using real-life data, inclusion of BRMs in the treatment strategy for RA appeared to be less favourable in our model than in most of the existing models that compared drug sequences independent of patient characteristics and used data from randomised controlled clinical trials. Despite complexity and demand for extensive data, our modelling approach can help to identify the knowledge gaps in clinical guidelines for RA management and priorities for future research. TI - Modelling outcomes of complex treatment strategies following a clinical guideline for treatment decisions in patients with rheumatoid arthritis EP - 1028 SN - 1170-7690 IS - iss. 10 SP - 1015 JF - Pharmacoeconomics VL - vol. 32 DO - http://dx.doi.org/10.1007/s40273-014-0184-4 ER - TY - JOUR AU - Siemons, L. AU - Vonkeman, H.E. AU - Klooster, P.M. ten AU - Riel, P.L.C.M. van AU - Laar, M.A. van der PY - 2014 UR - http://hdl.handle.net/2066/138331 AB - This paper aims to examine the interchangeability of the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-CRP scores in a diverse sample of rheumatoid arthritis (RA) patients and to evaluate generalizability over gender, age, and disease duration. A sample of 682 patients was drawn from the DREAM registry. Agreement between the two DAS28 scores was analyzed using the intraclass correlation coefficient (ICC), Bland Altman plots, and a matrix of classification agreement over DAS28 disease activity categories. Despite a strong linear correlation between the DAS28 scores and a high ICC value of 0.931, a considerable lack of individual agreement could be observed, with Bland-Altman 95 % limits of agreement ranging between -0.85 and +1.25 points. On average, DAS28-CRP scores were 0.20 points lower than DAS28-ESR scores, and data stratification on age and gender showed that this systematic bias was most severe in older women (0.39 points). The overall classification agreement across DAS28 categories was 76.69 %, with the agreement being lowest (35.37 %) in the low disease activity group. Patients were more easily classified as being in remission when using the DAS28-CRP measure. DAS28-ESR and DAS28-CRP scores are not interchangeable within individuals. The DAS28-CRP tends to yield lower values of disease activity than the DAS28-ESR, resulting in substantial classification differences. TI - Interchangeability of 28-joint disease activity scores using the erythrocyte sedimentation rate or the C-reactive protein as inflammatory marker EP - 789 SN - 0770-3198 IS - iss. 6 SP - 783 JF - Clinical Rheumatology VL - vol. 33 DO - https://doi.org/10.1007/s10067-014-2538-x ER - TY - JOUR AU - Siemons, L. AU - Klooster, P.M. ten AU - Vonkeman, H.E. AU - Riel, P.L.C.M. van AU - Glas, C.A. AU - Laar, M.A. van der PY - 2014 UR - http://hdl.handle.net/2066/139118 AB - BACKGROUND: The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are two commonly used measures of inflammation in rheumatoid arthritis (RA). As current RA treatment guidelines strongly emphasize early and aggressive treatment aiming at fast remission, optimal measurement of inflammation becomes increasingly important. Dependencies with age, sex, and body mass index have been shown for both inflammatory markers, yet it remains unclear which inflammatory marker is affected least by these effects in patients with early RA. METHODS: Baseline data from 589 patients from the DREAM registry were used for analyses. Associations between the inflammatory markers and age, sex, and BMI were evaluated first using univariate linear regression analyses. Next, it was tested whether these associations were independent of a patient's current disease activity as well as of each other using multiple linear regression analyses with backward elimination. The strengths of the associations were compared using standardized beta (beta) coefficients. The multivariate analyses were repeated after 1 year. RESULTS: At baseline, both the ESR and CRP were univariately associated with age, sex, and BMI, although the association with BMI disappeared in multivariate analyses. ESR and CRP levels significantly increased with age (beta-ESR = 0.017, p < 0.001 and beta-CRP = 0.009, p = 0.006), independent of the number of tender and swollen joints, general health, and sex. For each decade of aging, ESR and CRP levels became 1.19 and 1.09 times higher, respectively. Furthermore, women demonstrated average ESR levels that were 1.22 times higher than that of men (beta = 0.198, p = 0.007), whereas men had 1.20 times higher CRP levels (beta = -0.182, p = 0.048). Effects were strongest on the ESR. BMI became significantly associated with both inflammatory markers after 1 year, showing higher levels with increasing weight. Age continued to be significantly associated, whereas sex remained only associated with the ESR level. CONCLUSIONS: Age and sex are independently associated with the levels of both acute phase reactants in early RA, emphasizing the need to take these external factors into account when interpreting disease activity measures. BMI appears to become more relevant at later stages of the disease. TI - How age and sex affect the erythrocyte sedimentation rate and C-reactive protein in early rheumatoid arthritis SN - 1471-2474 IS - iss. 1 SP - 368 JF - BMC Musculoskeletal Disorders VL - vol. 15 DO - https://doi.org/10.1186/1471-2474-15-368 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/139118/139118.pdf?sequence=1 ER - TY - JOUR AU - Meek, I.L. AU - Vonkeman, H.E. AU - Laar, M.A. van der PY - 2014 UR - http://hdl.handle.net/2066/137605 AB - BACKGROUND: Previous studies found increased case fatality after myocardial infarction and more frequent sudden death in RA patients compared to non-RA subjects. The RA associated CV risk might be explained by the combined effects of chronic systemic inflammation and increased lifestyle associated cardiovascular risk factors, and modified by the use of medication such as non steroidal anti-inflammatory drugs, corticosteroids and disease modifying anti-rheumatic drugs. Trends in case fatality rate in RA after the introduction of potent anti-inflammatory biologic therapies and treat-to-target treatment strategies aiming at remission are not known. This study was performed to examine the cardiovascular fatality rate in current low disease activity RA, and to evaluate trends in RA associated CV case fatality over time. METHODS: Prospective study to determine the incidence of fatal and nonfatal CV events in 480 RA patients included in the ACT-CVD cohort between February 2009 and December 2011. Patients with prior CV disease were excluded. Cox regression analysis was performed to determine CV event risk and contributing risk factors over time. The results of the cohort analysis were put into the context of a review of the literature to evaluate trends in RA associated CV fatality rate over time. RESULTS: The study included 480 RA patients, 72.3% female with median disease duration of 4.2 years, 72.1% being in clinical remission (Disease Activity Score in 28 joints). During a mean follow up of 2.9 years 29 patients (6%) experienced a first CV event, 2 fatal and 27 non-fatal, corresponding to a 6.9% case fatality rate. Comparison with previous studies in cohorts with successive enrolment periods shows a trend towards a decrease in CV case fatality in RA from 52.9% in 1998 to 6.9% in our study. CONCLUSION: CV case fatality in current low disease activity RA is importantly lower than in previous studies, and a trend towards decreasing CV fatality in RA is suggested. TI - Cardiovascular case fatality in rheumatoid arthritis is decreasing; first prospective analysis of a current low disease activity rheumatoid arthritis cohort and review of the literature SN - 1471-2474 SP - 142 JF - BMC Musculoskeletal Disorders VL - vol. 15 DO - https://doi.org/10.1186/1471-2474-15-142 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/137605/137605.pdf?sequence=1 ER - TY - JOUR AU - Meek, I.L. AU - Vonkeman, H.E. AU - Laar, M.A. van der PY - 2014 UR - http://hdl.handle.net/2066/138195 AB - BACKGROUND: Gout and hyperuricaemia may be associated with increased cardiovascular risk, but analyses in different populations show conflicting results. This study investigates the impact of serum uric acid, inflammation and traditional CV risk parameters on CV event risk in patients with gouty arthritis and patients with non-gouty rheumatic disease. METHODS: cross-sectional and prospective multivariate analysis of the relation between tertiles of serum uric acid and individual traditional CV risk factors in a cohort of gouty arthritis (GA, n=172), rheumatoid arthritis (RA, n=480) and osteoarthritis (OA, n=206) patients. Main outcome measures: systolic blood pressure, TC/HDL ratio, GlyHb, BMI and first CV events. RESULTS: Individual CV risk factors were significantly less favourable in GA (systolic blood pressure, TC/HDL ratio, BMI, p<0.05). In RA and OA, but not in GA, individual cardiometabolic parameters correlated with serum uric acid values (OA: RA: systolic blood pressure, TC/HDL ratio, BMI; systolic blood pressure, TC/HDL ratio, GlyHb, BMI; p<0.05). In non-GA individuals the highest tertile of serum uric acid (>0.34 mmol/L) and NT proBNP level were independent predictors of first CV events, against age and GlyHb level in GA (p<0.05). The hazard of first CV events was equally significantly increased in GA patients (HR 3.169, 95% CI 1.287-7.806) and non-GA individuals with a serum uric acid >/= 0.34 mmol/L (HR 3.721, 95% CI 1.603-8.634) compared to non-GA individuals with a serum uric acid < 0.27. CONCLUSIONS: GA is associated with a 3.1-fold hazard of first CV events. In non-GA rheumatic patients increasing serum uric acid is associated with increased CV risk, whereas CV risk in GA is independent of serum uric acid values. The presence of GA or a baseline serum uric acid in the upper range are possibly stronger predictors of first CV events than some traditional CV risk factors or parameters of inflammation. TI - Hyperuricaemia: a marker of increased cardiovascular risk in rheumatic patients: analysis of the ACT-CVD cohort SN - 1471-2474 SP - 174 JF - BMC Musculoskeletal Disorders VL - vol. 15 DO - https://doi.org/10.1186/1471-2474-15-174 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/138195/138195.pdf?sequence=1 ER - TY - JOUR AU - Okada, Y. AU - Wu, D. AU - Trynka, G. AU - Raj, T. AU - Terao, C. AU - Ikari, K. AU - Kochi, Y. AU - Ohmura, K. AU - Suzuki, A. AU - Yoshida, S. AU - Graham, R.R. AU - Manoharan, A. AU - Ortmann, W. AU - Bhangale, T. AU - Denny, J.C. AU - Carroll, R.J. AU - Eyler, A.E. AU - Greenberg, J.D. AU - Kremer, J.M AU - Pappas, D.A. AU - Jiang, L. AU - Yin, J. AU - Ye, L AU - Su, D.F. AU - Yang, J. AU - Xie, G. AU - Keystone, E. AU - Westra, H.J. AU - Esko, T. AU - Metspalu, A. AU - Zhou, X. AU - Gupta, N. AU - Mirel, D. AU - Stahl, E.A. AU - Diogo, D. AU - Cui, J. AU - Liao, K. AU - Guo, M.H. AU - Myouzen, K. AU - Kawaguchi, T. AU - Coenen, M.J.H. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der AU - Guchelaar (LUMC), H.J. AU - Huizinga, T.W.J. AU - Dieude, P. AU - Mariette, X. AU - Bridges, S.L., Jr. AU - Zhernakova, A. AU - Toes, R.E. AU - Tak, P.P. AU - Miceli-Richard, C. AU - Bang, S.Y. AU - Lee, H.S. AU - Martin, J. AU - Gonzalez-Gay, M.A. AU - Rodriguez-Rodriguez, L. AU - Rantapaa-Dahlqvist, S. AU - Arlestig, L. AU - Choi, H.K. AU - Kamatani, Y. AU - Galan, P. AU - Lathrop, M. AU - Eyre, S. AU - Bowes, J. AU - Barton, A. AU - Vries, N. de AU - Moreland, L.W. AU - Criswell, L.A. AU - Karlson, E.W. AU - Taniguchi, A. AU - Yamada, R. AU - Kubo, M. AU - Liu, J.S. AU - Bae, S.C. AU - Worthington, J. AU - Padyukov, L. AU - Klareskog, L. AU - Gregersen, P.K. AU - Raychaudhuri, S. AU - Stranger, B.E. AU - Jager, P.L. De AU - Franke, L. AU - Visscher, P.M. AU - Brown, M.A. AU - Yamanaka, H. AU - Mimori, T. AU - Takahashi, A. AU - Xu, H. AU - Behrens, T.W. AU - Siminovitch, K.A. AU - Momohara, S. AU - Matsuda, F. AU - Yamamoto, K. AU - Plenge, R.M. AU - et al. PY - 2014 UR - http://hdl.handle.net/2066/138094 AB - A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating approximately 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses--as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes--to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery. TI - Genetics of rheumatoid arthritis contributes to biology and drug discovery EP - 381 SN - 0028-0836 IS - iss. 7488 SP - 376 JF - Nature VL - vol. 506 DO - https://doi.org/10.1038/nature12873 ER - TY - JOUR AU - Oude Voshaar, M.A. AU - Klooster, P.M. ten AU - Glas, C.A. AU - Vonkeman, H.E. AU - Taal, E. AU - Krishnan, E. AU - Moens, H.J. AU - Boers, M. AU - Terwee, C.B. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der PY - 2014 UR - http://repository.ubn.ru.nl/handle/2066/127702 AB - OBJECTIVE: To calibrate the Dutch-Flemish version of the PROMIS physical function (PF) item bank in patients with rheumatoid arthritis (RA) and to evaluate cross-cultural measurement equivalence with US general population and RA data. METHODS: Data were collected from RA patients enrolled in the Dutch DREAM registry. An incomplete longitudinal anchored design was used where patients completed all 121 items of the item bank over the course of three waves of data collection. Item responses were fit to a generalized partial credit model adapted for longitudinal data and the item parameters were examined for differential item functioning (DIF) across country, age, and sex. RESULTS: In total, 690 patients participated in the study at time point 1 (T2, N = 489; T3, N = 311). The item bank could be successfully fitted to a generalized partial credit model, with the number of misfitting items falling within acceptable limits. Seven items demonstrated DIF for sex, while 5 items showed DIF for age in the Dutch RA sample. Twenty-five (20%) items were flagged for cross-cultural DIF compared to the US general population. However, the impact of observed DIF on total physical function estimates was negligible. DISCUSSION: The results of this study showed that the PROMIS PF item bank adequately fit a unidimensional IRT model which provides support for applications that require invariant estimates of physical function, such as computer adaptive testing and targeted short forms. More studies are needed to further investigate the cross-cultural applicability of the US-based PROMIS calibration and standardized metric. TI - Calibration of the PROMIS Physical Function Item Bank in Dutch Patients with Rheumatoid Arthritis SN - 1932-6203 IS - iss. 3 JF - PLoS One VL - vol. 9 DO - https://doi.org/10.1371/journal.pone.0092367 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/127702/127702.pdf?sequence=1 ER - TY - JOUR AU - Dartel, S.A.A. van AU - Fransen, J. AU - Kievit, W. AU - Dutmer, E.A. AU - Brus, H.L. AU - Houtman, N.M. AU - Laar, M.A. van der AU - Riel, P.L.C.M. van PY - 2013 UR - http://hdl.handle.net/2066/117464 AB - Objective. The use of TNF inhibitors leads to an increased risk of serious infections in RA. Predicting this risk would facilitate the prevention of serious infections. The objective of this study was to identify which factors are predictive of the increased risk of serious infections in RA patients treated with TNF inhibiting therapy. Methods. Data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry of 2044 patients with RA were used for the analyses. Data were censored at stopping TNF inhibitors or end of observation time up to 5 years. Univariate and multivariate analysis of baseline variables was performed using Cox regression with time to the first serious infection as dependent variable. Results. During a follow-up time of 5 years, 128 of 2044 (6.3%) patients developed a first serious infection with a total of 141 serious infections. The incidence rate in the first year after start of TNF inhibiting therapy was 4.57 first serious infections per 100 patient-years and 2.91 per 100 patient-years over 5 years. Age, corticosteroid use, visual analogue scale (VAS) pain, HAQ, tender joint count 28 joints (TJC28) and the presence of comorbidities were significant predictors for developing a serious infection during TNF inhibiting therapy in the multivariate model. Conclusion. Age, corticosteroid use, VAS pain, HAQ, TJC28 and the presence of comorbidities all at baseline were significant predictors for developing a serious infection during TNF inhibiting therapy in RA patients. TI - Predictors for the 5-year risk of serious infections in patients with rheumatoid arthritis treated with anti-tumour necrosis factor therapy: a cohort study in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry EP - 1057 SN - 1462-0324 IS - iss. 6 SP - 1052 JF - Rheumatology VL - vol. 52 DO - http://dx.doi.org/10.1093/rheumatology/kes413 ER - TY - JOUR AU - Siemons, L. AU - Klooster, P.M. ten AU - Taal, E. AU - Kuper, I.H. AU - Riel, P.L. van AU - Glas, C.A. AU - Laar, M.A. van der PY - 2013 UR - http://hdl.handle.net/2066/118217 AB - OBJECTIVE: To evaluate the contribution of assessing forefoot joints to the measurement range and measurement precision of joint counts in early rheumatoid arthritis (RA) using item response theory. METHODS: Baseline measures of tender and swollen joint counts were analyzed in 459 early RA patients from the Dutch Rheumatoid Arthritis Monitoring remission induction cohort. The contribution of forefoot joints was studied by evaluating their effect on the measurement range and measurement precision of measures based on 28-joint counts. In addition, the alignment between the patient and joint distributions was investigated to determine whether the forefoot joints were informative for measuring joint tenderness or swelling of an early RA patient. RESULTS: In total, 233 patients (50.76%) experienced tenderness and 200 patients (43.57%) experienced swelling in >/=1 forefoot joint. Forefoot joints were more informative for measuring joint tenderness than joint swelling, but did not significantly improve the measurement range and measurement precision of the 28-joint counts. Furthermore, including forefoot joints did not remove the existing discrepancy between the joint and patient distributions in both joint counts. CONCLUSION: Forefoot joints were frequently affected on an individual level, but did not significantly improve the measurement range or precision of 28-joint counts in patients with early RA. From a measurement perspective, reduced joint counts are appropriate for use on a population level. The contribution of assessing forefoot joints on an individual level requires further investigation. Additionally, the results should be cross-validated in patients with longer disease durations to determine whether the pattern of joint involvement is similar in later stages of RA. TI - Contribution of assessing forefoot joints in early rheumatoid arthritis patients: insights from item response theory EP - 219 SN - 2151-464X IS - iss. 2 SP - 212 JF - Arthritis Care & Research VL - vol. 65 DO - https://doi.org/10.1002/acr.21795 ER - TY - JOUR AU - Dartel, S.A.A. van AU - Fransen, J. AU - Kievit, W. AU - Flendrie, M. AU - Broeder, A. den AU - Visser, H. AU - Hartkamp, A. AU - Laar, M.A. van der AU - Riel, P.L.C.M. van PY - 2013 UR - http://hdl.handle.net/2066/118288 AB - BACKGROUND: Tumour necrosis factor (TNF)-inhibiting therapy increases the risk of serious infections in rheumatoid arthritis (RA). However, it is not clear whether this risk differs between TNF inhibitors. OBJECTIVE: To analyse whether the risk of serious infections in patients with RA treated with an anti-TNF inhibitor is different for adalimumab, infliximab and etanercept. METHODS: Data from the Dutch RA monitoring registry were used. Incidence rates were calculated from the observed number of first serious infections and follow-up time up to 5 years. A Cox proportional hazards model with time-to-first-serious infection was used to estimate risk differences among the anti-TNF treatment groups, with correction for confounders. RESULTS: The unadjusted incidence rate of a first serious infection in patients with RA per 100 patient-years was 2.61 (95% CI 2.21 to 3.00) for adalimumab, 3.86 (95% CI 3.33 to 4.40) for infliximab and 1.66 (95% CI 1.09 to 2.23) for etanercept. Age, year of starting anti-TNF therapy, comorbidities at baseline and disease activity score 28 over time were included as confounders. No difference in risk for serious infections was found between adalimumab and infliximab with an adjusted HR (adjHR) of 0.90 (95% CI 0.55 to 1.48). The risk of serious infections was significantly lower in etanercept than in both infliximab (adjHR=0.49 (95% CI 0.29 to 0.83)) and adalimumab (adjHR=0.55 (95% CI 0.44 to 0.67)). CONCLUSIONS: The risk of serious infections in patients with RA treated with adalimumab or infliximab was similar, while the risk of serious infections in patients with RA treated with etanercept was lower than with both adalimumab and infliximab. TI - Difference in the risk of serious infections in patients with rheumatoid arthritis treated with adalimumab, infliximab and etanercept: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry EP - 900 SN - 0003-4967 IS - iss. 6 SP - 895 JF - Annals of the Rheumatic Diseases VL - vol. 72 ER - TY - JOUR AU - Klooster, P.M. ten AU - Vonkeman, H.E. AU - Taal, E. AU - Siemons, L. AU - Hendriks, L. AU - Jong, A.J.L. de AU - Dutmer, E.A. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der PY - 2013 UR - http://hdl.handle.net/2066/118944 AB - BACKGROUND: The aim of this study was to examine the measurement properties of the Dutch SF-36 version 2 (SF-36v2) health survey in patients with rheumatoid arthritis (RA). METHODS: Scaling assumptions, internal reliability, and internal construct validity were examined using available data from 1884 RA patients included in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. External construct validity and responsiveness to change were examined using baseline and 6-month follow-up data from a subset of 387 early RA patients participating in the DREAM remission induction cohort. RESULTS: The individual items of the SF-36v2 adequately met scaling assumptions, although four items correlated too highly with items from different scales. Internal consistency was high for all eight scales and the physical and mental health components underlying the scales were replicated, supporting the use of the standard scoring algorithms. The SF-36v2 scales demonstrated minimal floor effects and ceiling effects were noteworthy only for the role-physical, social functioning, and role-emotional scales. Correlations with other core measures were as expected and the SF-36v2 showed excellent known-groups validity in distinguishing between patients with low or moderate-high disease activity. All scales related to physical health showed moderate to large responsiveness to change in patients that achieved low disease activity at six months. CONCLUSION: The SF-36v2 appears to be a psychometrically sound tool for the assessment of health-related quality of life of Dutch patients with RA. TI - Performance of the Dutch SF-36 version 2 as a measure of health-related quality of life in patients with rheumatoid arthritis SN - 1477-7525 SP - 77 JF - Health and Quality of Life Outcomes VL - vol. 11 DO - http://dx.doi.org/10.1186/1477-7525-11-77 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/118944/118944.pdf?sequence=1 ER - TY - JOUR AU - Voshaar, M.A. AU - Klooster, P.M. ten AU - Vonkeman, H.E. AU - Kievit, W. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der PY - 2013 UR - http://hdl.handle.net/2066/125645 TI - Measurement bias in different versions of the Dutch Health Assessment Questionnaire Disability Index EP - 2051 SN - 0003-4967 IS - iss. 12 SP - 2050 JF - Annals of the Rheumatic Diseases VL - vol. 72 DO - https://doi.org/10.1136/annrheumdis-2013-203512 ER - TY - JOUR AU - Vaart, R. van der AU - Repping-Wuts, H. AU - Drossaert, C.H. AU - Taal, E. AU - Knaapen-Hans, H.K. AU - Laar, M.A. van der PY - 2013 UR - http://hdl.handle.net/2066/125700 AB - OBJECTIVE: Interactive health communication applications (IHCAs) offer interesting possibilities to support systemic sclerosis (SSc) patients, since SSc is an uncommon, severe disease that needs a multidisciplinary treatment. This study aimed to investigate patients' needs for a hospital-based IHCA. METHODS: A survey study was conducted among a large sample (n = 429) of SSc patients of the University Medical Centre St. Radboud in Nijmegen, The Netherlands. Patients were asked about their current disease-related internet use, their perceived importance of diverse information topics, and their usefulness of 8 widely used online health services. To examine how disease specific their needs were, the results of SSc patients were compared with the results of a sample of rheumatoid arthritis (RA) patients (n = 1,284). RESULTS: In total, 746 patients (44% of the approached patients) returned a completed questionnaire and fulfilled all of the inclusion criteria. Of them, 569 (76%) had internet access. SSc patients used the internet especially for information (85%), and they expressed a need for information on physical, psychological, and social consequences of the disease. Concerning a hospital-based IHCA, e-consults, information about disease and treatment, and home access to their electronic medical records were perceived as most useful. SSc patients were more positive about the usefulness of the online applications than were RA patients, especially for e-consults and peer support forums. CONCLUSION: It would be valuable to offer SSc patients a hospital-based IHCA, including the online information and support they desire. When taking the needs of patients into account, an IHCA could become a valuable addition to their regular treatment. TI - Need for online information and support of patients with systemic sclerosis EP - 600 SN - 2151-464X IS - iss. 4 SP - 594 JF - Arthritis Care & Research VL - vol. 65 DO - https://doi.org/10.1002/acr.21875 ER - TY - JOUR AU - Vermeer, M. AU - Kievit, W. AU - Kuper, H.H. AU - Braakman-Jansen, L.M. AU - Bernelot Moens, H.J. AU - Zijlstra, T.R. AU - Broeder, A.A. den AU - Riel, P.L. van AU - Fransen, J. AU - Laar, M.A. van der PY - 2013 UR - http://hdl.handle.net/2066/126177 TI - Treating to the target of remission in early rheumatoid arthritis is cost-effective: results of the DREAM registry. EP - 350 SN - 1471-2474 IS - iss. 1 SP - 350 JF - BMC Musculoskeletal Disorders VL - vol. 14 DO - http://dx.doi.org/10.1186/1471-2474-14-350 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/126177/126177.pdf?sequence=1 ER - TY - JOUR AU - Vermeer, M. AU - Kuper, H.H. AU - Moens, H.J. AU - Drossaers-Bakker, K.W. AU - Bijl, A.E. van der AU - Riel, P.L.C.M. van AU - Laar, M.A. van der PY - 2013 UR - http://hdl.handle.net/2066/189154 AB - OBJECTIVE: Treat-to-target (T2T) leads to improved clinical outcomes in early rheumatoid arthritis (RA). The question is whether these results sustain in the long term. Our objective was to investigate the 3-year results of a protocolized T2T strategy in daily clinical practice. METHODS: In the Dutch Rheumatoid Arthritis Monitoring remission induction cohort, patients newly diagnosed with RA were treated according to a T2T strategy aimed at remission (Disease Activity Score in 28 joints [DAS28] <2.6). Patients were treated with methotrexate, followed by the addition of sulfasalazine, and exchange of sulfasalazine with anti-tumor necrosis factor alpha agents in case of failure. Primary outcomes were disease activity, Health Assessment Questionnaire (HAQ) score, Short Form 36 physical component summary (PCS) and mental component summary (MCS) scores, and the Sharp/van der Heijde score (SHS) after 3 years. Secondary outcomes were sustained DAS28 remission (>/=6 months) and remission according to the provisional American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) definition. RESULTS: After 3 years (n = 342), 61.7% of patients were in DAS28 remission and 25.3% met the provisional ACR/EULAR definition of remission. Sustained remission was experienced by 70.5%, which in the majority was achieved with conventional disease-modifying antirheumatic drugs only. The median scores were 0.4 (interquartile range [IQR] 0.0-1.0) for the HAQ, 45.0 (IQR 38.4-53.2) for the PCS, 53.1 (IQR 43.2-60.8) for the MCS, and 6.0 (IQR 3.0-13.0) for the total SHS. CONCLUSION: In very early RA, T2T leads to high (sustained) remission rates, improved physical function and health-related quality of life, and limited radiographic damage after 3 years in daily clinical practice. TI - Sustained beneficial effects of a protocolized treat-to-target strategy in very early rheumatoid arthritis: three-year results of the Dutch Rheumatoid Arthritis Monitoring remission induction cohort EP - 1226 SN - 2151-464X IS - iss. 8 SP - 1219 JF - Arthritis Care & Research VL - vol. 65 DO - https://doi.org/10.1002/acr.21984 ER - TY - JOUR AU - Meek, I.L. AU - Picavet, H.S. AU - Vonkeman, H.E. AU - Verschuren, W.M. AU - Laar, M.A. van der PY - 2013 UR - http://hdl.handle.net/2066/118644 AB - OBJECTIVES: To study the prevalence of cardiovascular risk factors among patients attending a rheumatology outpatient clinic in comparison with the general population. METHODS: Cross-sectional comparison between a rheumatic outpatient cohort of consecutive patients (n = 1233) between 36 and 75 years of age attending the Arthritis Center Twente (ACT) in the year 2009: RA (n = 546), gout (n = 129), OA (n = 168), CTD (n = 85), PMR (n = 91) and chronic localized or generalized pain syndromes (CPSs; n = 214) and a random sample from a long-lasting population-based health study in the Netherlands (n = 4523). The main outcome measures were hypertension (systolic blood pressure >/= 140 mmHg and/or a diastolic blood pressure >/= 90 mmHg and/or the use of antihypertensive medication), abnormal cholesterol profile (total cholesterol >/= 6.5 mmol/l, and/or high-density lipoprotein < 0.9 mmol/l and/or use of lipid lowering medication), overweight (BMI >/= 25 kg/m(2)), obesity (BMI >/= 30 kg/m(2)) and cigarette smoking habits (self-reported current smoking). RESULTS: Compared with the general population, patients with rheumatic diseases have a significantly higher prevalence of hypertension (P(ACT) = 68%, P(general) = 57%), being overweight (P(ACT) = 72%, P(general) = 62%), obesity (P(ACT) = 30%, P(general) = 17%) and cigarette smoking (P(ACT) = 26%, P(general) = 21%). The worst risk profile was found in gout patients, with higher prevalence of all cardiovascular risk factors studied. CONCLUSION: Lifestyle-associated potentially modifiable cardiovascular risk factors are over-represented along the whole spectrum of chronic rheumatic diseases, and not only in RA, as suggested by preceding studies. TI - Increased cardiovascular risk factors in different rheumatic diseases compared with the general population EP - 216 SN - 1462-0324 IS - iss. 1 SP - 210 JF - Rheumatology VL - vol. 52 DO - https://doi.org/10.1093/rheumatology/kes194 ER - TY - JOUR AU - Meek, I.L. AU - Vonkeman, H.E. AU - Kasemier, J. AU - Movig, K.L.L. AU - Laar, M.A. van der PY - 2013 UR - http://hdl.handle.net/2066/118673 AB - PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed concurrently in patients with nociceptive pain and cardiovascular comorbidity. NSAIDs and ASA inhibit the same COX-enzymes, and thus may interact. ASA's cardioprotective antiplatelet effect is entirely COX-1 dependent. NSAIDs can be either non-COX-1 and COX-2 selective or COX-2 selective. The aim of this study was to examine the interaction between ASA and different selective and nonselective NSAIDs on thrombocyte function. METHODS: Single-blind, prospective, placebo-controlled, ex vivo, serial crossover trial of 3-day cycles separated by washout periods of at least 12 days in 30 healthy volunteers, evaluating interaction on ASA's antithrombocyte effect by naproxen, ibuprofen, meloxicam, or etoricoxib taken 2 h before ASA. Ex vivo thrombocyte function, closure time (CT) in seconds, was measured using the Platelet Function Analyzer 100 (PFA-100). CT prolongation during a cycle reflects thrombocyte inhibitory effect. ASA nonresponse was defined as CT prolongation <40 % in the placebo cycle. ASA nonresponders were excluded. Wilcoxon signed-rank was used to evaluate NSAID effect on ASA-induced CT prolongation. RESULTS: Ibuprofen and naproxen inhibit ASA's antithrombocyte effect below the nonresponse threshold. Etoricoxib and meloxicam do not cause relevant change in ASA thrombocyte inhibition. Naproxen has an inherent weak thrombocyte inhibitory action below the ASA response threshold. CONCLUSIONS: COX-1 affinity determines the interaction between NSAIDs and ASA on thrombocyte adhesion and aggregation. Ibuprofen and naproxen, but not etoricoxib or meloxicam, taken 2 h before ASA, significantly inhibit ASA's antithrombocyte effect. TI - Interference of NSAIDs with the thrombocyte inhibitory effect of aspirin: a placebo-controlled, ex vivo, serial placebo-controlled serial crossover study EP - 371 SN - 0031-6970 IS - iss. 3 SP - 365 JF - European Journal of Clinical Pharmacology VL - vol. 69 DO - https://doi.org/10.1007/s00228-012-1370-y ER - TY - JOUR AU - Prowse, R.L. AU - Dalbeth, N. AU - Kavanaugh, A. AU - Adebajo, A.O. AU - Gaffo, A.L. AU - Terkeltaub, R. AU - Mandell, B.F. AU - Suryana, B.P. AU - Goldenstein-Schainberg, C. AU - Diaz-Torne, C. AU - Khanna, D. AU - Liote, F. AU - McCarthy, G. AU - Kerr, G.S. AU - Yamanaka, H. AU - Janssens, H. AU - Baraf, H.F. AU - Chen, J.H. AU - Vazquez-Mellado, J. AU - Harrold, L.R. AU - Stamp, L.K. AU - Laar, M.A. van der AU - Janssen, M. AU - Doherty, M. AU - Boers-Sonderen, M.J. AU - Edwards, N.L. AU - Gow, P. AU - Chapman, P. AU - Khanna, P. AU - Helliwell, P.S. AU - Grainger, R. AU - Schumacher, H.R. AU - Neogi, T. AU - Jansen, T.L.Th.A. AU - Louthrenoo, W. AU - Sivera, F. AU - Taylor, W.J. PY - 2013 UR - http://hdl.handle.net/2066/117844 AB - OBJECTIVE: To identify a comprehensive list of features that might discriminate between gout and other rheumatic musculoskeletal conditions, to be used subsequently for a case-control study to develop and test new classification criteria for gout. METHODS: Two Delphi exercises were conducted using Web-based questionnaires: one with physicians from several countries who had an interest in gout and one with patients from New Zealand who had gout. Physicians rated a list of potentially discriminating features that were identified by literature review and expert opinion, and patients rated a list of features that they generated themselves. Agreement was defined by the RAND/UCLA disagreement index. RESULTS: Forty-four experienced physicians and 9 patients responded to all iterations. For physicians, 71 items were identified by literature review and 15 more were suggested by physicians. The physician survey showed agreement for 26 discriminatory features and 15 as not discriminatory. The patients identified 46 features of gout, for which there was agreement on 25 items as being discriminatory and 7 items as not discriminatory. CONCLUSION: Patients and physicians agreed upon several key features of gout. Physicians emphasized objective findings, imaging, and patterns of symptoms, whereas patients emphasized severity, functional results, and idiographic perception of symptoms. TI - A Delphi Exercise to Identify Characteristic Features of Gout -- Opinions from Patients and Physicians, the First Stage in Developing New Classification Criteria EP - 505 SN - 0315-162X IS - iss. 4 SP - 498 JF - The Journal of Rheumatology VL - vol. 40 DO - https://doi.org/10.3899/jrheum.121037 ER - TY - JOUR AU - Umicevic-Mirkov, M. AU - Cui, J. AU - Vermeulen, S. AU - Stahl, E.A. AU - Toonen, E.J.M. AU - Makkinje, R.R. AU - Lee, A.T. AU - Huizinga, T.W.J. AU - Allaart, R. AU - Barton, A. AU - Mariette, X. AU - Miceli, C.R. AU - Criswell, L.A. AU - Tak, P.P. AU - Vries, N de AU - Saevarsdottir, S. AU - Padyukov, L. AU - Bridges Jr, S.L. AU - Schaardenburg, D.J. van AU - Jansen, T.L.Th.A. AU - Dutmer, E.A. AU - Laar, M.A. van der AU - Barrera, P. AU - Radstake, T.R.D.J. AU - Riel, P.L.C.M. van AU - Scheffer, H. AU - Franke, B. AU - Brunner, H.G. AU - Plenge, R.M. AU - Gregersen, P.K. AU - Guchelaar (LUMC), H.J. AU - Coenen, M.J.H. PY - 2013 UR - http://hdl.handle.net/2066/118482 AB - BACKGROUND: Treatment strategies blocking tumour necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA). However, a significant subset of patients does not respond for unknown reasons. Currently, there are no means of identifying these patients before treatment. This study was aimed at identifying genetic factors predicting anti-TNF treatment outcome in patients with RA using a genome-wide association approach. METHODS: We conducted a multistage, genome-wide association study with a primary analysis of 2 557 253 single-nucleotide polymorphisms (SNPs) in 882 patients with RA receiving anti-TNF therapy included through the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry and the database of Apotheekzorg. Linear regression analysis of changes in the Disease Activity Score in 28 joints after 14 weeks of treatment was performed using an additive model. Markers with p<10(-3) were selected for replication in 1821 patients from three independent cohorts. Pathway analysis including all SNPs with p<10(-3) was performed using Ingenuity. RESULTS: 772 markers showed evidence of association with treatment outcome in the initial stage. Eight genetic loci showed improved p value in the overall meta-analysis compared with the first stage, three of which (rs1568885, rs1813443 and rs4411591) showed directional consistency over all four cohorts studied. We were unable to replicate markers previously reported to be associated with anti-TNF outcome. Network analysis indicated strong involvement of biological processes underlying inflammatory response and cell morphology. CONCLUSIONS: Using a multistage strategy, we have identified eight genetic loci associated with response to anti-TNF treatment. Further studies are required to validate these findings in additional patient collections. TI - Genome-wide association analysis of anti-TNF drug response in patients with rheumatoid arthritis EP - 1381 SN - 0003-4967 IS - iss. 8 SP - 1375 JF - Annals of the Rheumatic Diseases VL - vol. 72 DO - https://doi.org/10.1136/annrheumdis-2012-202405 ER - TY - JOUR AU - Schipper, L.G. AU - Vermeer, M. AU - Kuper, H.H. AU - Hoekstra, M.O. AU - Haagsma, C.J. AU - Broeder, A. den AU - Riel, P.L.C.M. van AU - Fransen, J. AU - Laar, M.A. van der PY - 2012 UR - http://hdl.handle.net/2066/108181 AB - There is strong evidence from clinical trials that a 'treat to target' strategy is effective in reaching remission in rheumatoid arthritis (RA). However, the question is whether these results can be translated into daily clinical practice and clinical remission is a reachable target indeed. OBJECTIVE: The study aims to investigate whether in early RA a treatment strategy aiming at Disease Activity Score (DAS) 28 <2.6 is more effective than 'usual care' treatment for reaching clinical remission after 1 year. METHODS: Two early RA inception cohorts from two different regions including patients who fulfilled the American College of Rheumatology criteria for RA were compared. Patients in the tight-control cohort (n=126) were treated according to a DAS28-driven step-up treatment strategy starting with methotrexate, addition of sulphasalazine (SSZ) and exchange of SSZ by anti-tumour necrosis factor in case of failure. Patients in the usual-care cohort (n=126) were treated with methotrexate or SSZ, without DAS28-guided treatment decisions. The primary outcome was the percentage remission (DAS28<2.6) at 1 year. Time to first remission and change in DAS28 were secondary outcomes. RESULTS: After 1 year, 55% of tight-control patients had a DAS28<2.6 versus 30% of usual care patients (OR 3.1, 95% CI 1.8 to 5.2). The median time to first remission was 25 weeks for tight control and more than 52 weeks for usual care (p<0.0001). The DAS28 decreased with -2.5 in tight control and -1.5 in usual care (p<0.0001). CONCLUSION: In early RA, a tight control treatment strategy aiming for remission leads to more rapid DAS28 remission and higher percentages of remission after 1 year than does a usual care treatment. TI - A tight control treatment strategy aiming for remission in early rheumatoid arthritis is more effective than usual care treatment in daily clinical practice: a study of two cohorts in the Dutch Rheumatoid Arthritis Monitoring registry. EP - 850 SN - 0003-4967 IS - iss. 6 SP - 845 JF - Annals of the Rheumatic Diseases VL - vol. 71 N1 - 1 juni 2012 DO - https://doi.org/10.1136/annrheumdis-2011-200274 ER - TY - JOUR AU - Punder, Y.M.R. de AU - Fransen, J. AU - Kievit, W. AU - Houtman, P.M. AU - Visser, H. AU - Laar, M.A. van der AU - Riel, P.L.C.M. van PY - 2012 UR - http://hdl.handle.net/2066/109904 AB - Objectives. To evaluate the prevalence of clinical remission and minimal disease activity according to the ACR/European League Against Rheumatism (EULAR) remission, DAS-28 <2.6 and minimal disease activity (MDA) criteria, and to compare the extent of residual disease activity with disability in RA patients after 6 months of treatment with anti-TNF. Methods. In the Dutch Rheumatoid Arthritis Monitoring (DREAM) biologic registry the prevalence of DAS-28 <2.6, MDA and ACR/EULAR remission criteria was assessed. Residual disease activity during MDA or remission was assessed as the percentage of patients with swollen and tender joints, elevated acute-phase reactants and general health on a visual analogue scale (VAS). Disability was evaluated with the HAQ score. Results. Prevalence of DAS-28 <2.6 was 27%, prevalence of MDA was 34% and ACR/EULAR remission was reached by 6% of patients. Residual disease activity was present mostly in the most lenient criteria and occurred most frequently on the level of swollen joint count and VAS score: at least one swollen joint in DAS-28 <2.6, MDA and ACR/EULAR remission was present in, respectively, 51, 54 and 34% of the patients. VAS >1 occurred in, respectively, 67, 69 and 0% of the patients. Modification of the cut-point of the patient-reported outcome increased the prevalence of ACR/EULAR remission, but also the level of disability. Conclusion. MDA and DAS-28 <2.6 are reachable treatment targets in RA with anti-TNF, although residual disease activity might still be present. In turn, ACR/EULAR remission criteria leave little residual disease activity, but might be too stringent for use in daily clinical practice due to the strict cut-point in the patient-reported outcome. TI - The prevalence of clinical remission in RA patients treated with anti-TNF: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. EP - 1617 SN - 1462-0324 IS - iss. 9 SP - 1610 JF - Rheumatology VL - vol. 51 N1 - 1 september 2012 DO - https://doi.org/10.1093/rheumatology/kes078 ER - TY - JOUR AU - Vermeer, M. AU - Kuper, H.H. AU - Bijl, A.E. van der AU - Baan, H. AU - Posthumus, M.D. AU - Brus, H.L. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der PY - 2012 UR - http://hdl.handle.net/2066/109910 AB - OBJECTIVES: The provisional ACR/European League Against Rheumatism (EULAR) definition of remission in RA requires a score of 1 despite fulfilment of the remaining criteria (TJC28, SJC28 and CRP in mg/dl 1. Receiver operating characteristic analysis showed moderate accuracy of the PGA to discriminate between fulfilment and no fulfilment of all remaining criteria. CONCLUSION: Frequently, patients did not meet the PGA criterion despite a good clinical disease state. Apparently the PGA is not solely influenced by RA disease activity. In patients with marked divergence between the PGA and objective clinical measurements, caution should be taken when applying the provisional ACR/EULAR definition of remission. TI - The provisional ACR/EULAR definition of remission in RA: a comment on the patient global assessment criterion. EP - 1080 SN - 1462-0324 IS - iss. 6 SP - 1076 JF - Rheumatology VL - vol. 51 N1 - 1 juni 2012 DO - https://doi.org/10.1093/rheumatology/ker425 ER - TY - JOUR AU - Buitinga, L. AU - Braakman-Jansen, L.M. AU - Taal, E. AU - Kievit, W. AU - Visser, H. AU - Riel, P.L.C.M. van AU - Laar, M.A. van der PY - 2012 UR - http://hdl.handle.net/2066/110623 AB - OBJECTIVE: For cost-utility analyses of health technologies, utilities are commonly measured with the EuroQol-5D (EQ-5D) or the Short Form 6D (SF-6D). Although most studies in rheumatoid arthritis (RA) found the SF-6D to be more responsive than the EQ-5D, evidence is not convincing. The aim of this study was to compare the responsiveness of the EQ-5D and SF-6D to improvement in RA patients treated with tumor necrosis factor (TNF) blockers. METHODS: Data from 278 RA patients included in the Dutch Rheumatoid Arthritis Monitoring registry were used. Internal responsiveness over 1 year was evaluated by using standardized response means (SRMs). External responsiveness was evaluated by using receiver operating characteristic curves based on perceived health change (self-reported health transition item Short Form 36) and change in disease activity (European League Against Rheumatism response criteria based on the Disease Activity Score in 28 joints). RESULTS: The scores of the EQ-5D and SF-6D changed moderately over 1 year (SRMs 0.50 and 0.67, respectively). The SF-6D was significantly more responsive to treatment than the EQ-5D. The EQ-5D and SF-6D were moderately able to correctly classify patients according to health transition (areas under the curve [AUCs] 0.67 and 0.72, respectively) and change in disease activity (AUCs 0.71 and 0.65, respectively). CONCLUSION: The EQ-5D and SF-6D were only moderately responsive to improvement in RA patients treated with TNF blockers. Overall, the SF-6D was more responsive than the EQ-5D. TI - Comparative responsiveness of the EuroQol-5D and Short Form 6D to improvement in patients with rheumatoid arthritis treated with tumor necrosis factor blockers: results of the Dutch Rheumatoid Arthritis Monitoring registry. EP - 832 SN - 2151-464X IS - iss. 6 SP - 826 JF - Arthritis Care & Research VL - vol. 64 N1 - 1 juni 2012 DO - https://doi.org/10.1002/acr.21619 ER - TY - JOUR AU - Jansen, T.L. AU - van Hulst, L.T. AU - Laar, M.A. van der AU - van Riel, P.L. AU - Albada-Kuipers, G.A. van PY - 2011 UR - http://hdl.handle.net/2066/97196 TI - POEET-studie: horizon bij behandeling met biologicals bepalen. EP - 5 SN - 1876-1143 SP - 4 JF - Rheumatology News International VL - vol. 2 ER - TY - JOUR AU - Schipper, L.G. AU - Kievit, W. AU - Broeder, A. den AU - Laar, M.A. van der AU - Adang, E.M.M. AU - Fransen, J. AU - Riel, P.L.C.M. van PY - 2011 UR - http://hdl.handle.net/2066/97472 AB - OBJECTIVE: To perform a modelling study on the cost-effectiveness of three outcome-directed strategies in early RA patients: Strategy 1: starting MTX monotherapy, followed by the addition of LEF, followed by MTX with addition of anti-TNF; Strategy 2: start with MTX and LEF combination followed by MTX with anti-TNF; and Strategy 3: immediate start with MTX and anti-TNF. METHODS: A validated Markov model was used to evaluate the cost-effectiveness of the three strategies. Effectiveness of the strategies was determined using daily practice data from two cohorts and used as input parameter in the model. Patients treated according to the strategies were matched for baseline 28-joint DAS (DAS-28). Using Monte Carlo simulation, expected costs, quality-adjusted life-years (QALYs) and incremental cost per QALY gained for a 5-year time horizon were calculated following both a health-care and a societal perspective. RESULTS: The percentage of patients in remission and number of QALYs were comparable between the three strategies. Starting with a combination (MTX plus LEF or anti-TNF) was more costly than starting with MTX alone. This resulted in an unfavourable incremental cost-effectiveness ratio for starting on anti-TNF vs initially MTX: health-care perspective of euro138,028 and from a societal perspective of euro136,150 per QALY gained over 5 years. CONCLUSION: In this modelling study, starting with MTX or anti-TNF has comparable effectiveness. However, initial anti-TNF was far more expensive than starting with MTX monotherapy. Therefore, based on this study, a treatment strategy starting with MTX monotherapy is favoured over a strategy with MTX and anti-TNF right away in early RA patients. TI - Treatment strategies aiming at remission in early rheumatoid arthritis patients: starting with methotrexate monotherapy is cost-effective EP - 1330 SN - 1462-0324 IS - iss. 7 SP - 1320 JF - Rheumatology VL - vol. 50 DO - http://dx.doi.org/10.1093/rheumatology/ker084 ER - TY - JOUR AU - Bijlsma, J.W.J. AU - Hagemeijer, J.W. AU - Bijl, M. van der AU - Jansen, T.L.Th.A. AU - Laar, M.A. van der AU - Landewe, R.B. AU - Nurmohamed, M.T. PY - 2011 UR - http://hdl.handle.net/2066/98548 AB - - A multidisciplinary working group has developed a practice guideline containing various recommendations on the responsible and efficient use of biologicals.- These biologicals include both soluble immune-receptor proteins and monoclonal antibodies that are aimed at immune mediators, receptors or cells. They are produced by biotechnology.- Biologicals are used to treat patients with immune-mediated inflammatory disorders (IMIDs) such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis, juvenile idiopathic arthritis (JIA), psoriasis, ulcerative colitis, Crohn's disease, uveitis and sarcoidosis.- This article summarises the most important recommendations contained in the practice guideline. The practice guideline is intended for members of the medical profession in addition to patients, who are considering, or are already, using biologicals. TI - [The multidisciplinary practice guideline 'The responsible use of biologicals']. EP - A3114 SN - 0028-2162 IS - iss. 30-31 SP - A3114 JF - Nederlands Tijdschrift voor Geneeskunde VL - vol. 155 ER - TY - JOUR AU - Brinkman, I.H. AU - Laar, M.A. van der AU - Jansen, T.L.Th.A. AU - Roon, E.N. van PY - 2011 UR - http://hdl.handle.net/2066/97447 AB - INTRODUCTION: Biologicals are a fast expanding group of new drugs and rituximab (RTX) is one of them. Long-term efficacy and safety constantly need addressing as little is known about these factors. In rheumatoid arthritis, RTX it is used for active disease that is not responding to other therapies. Since RTX acts by depleting B-cells, concerns regarding the long-term safety of this drug have been raised. AREAS COVERED: This review covers 10 manuscripts on RTX safety in rheumatoid arthritis published between January 2004 and July 2010. EXPERT OPINION: In present literature RTX appears to be safe for up to five courses. In this review, important drawbacks of current research are discussed. Longer follow-up time is needed to make relevant conclusions on RTX safety with regard to infectious complications. Prolonged RTX therapy causes subsequent B-cell depletion. Eventually, plasma cells disappear, causing hypogammaglobulinemias and subsequent problems in immunity. The formation of new plasma cells is halted due to a lack of B-cells. Attention needs to be focused on the status of immunoglobulins and the role this plays in the occurrence of infections. Until a complete, long-term safety profile of RTX is available, it cannot be considered safe with regard to the incidence of infectious complications. TI - The potential risk of infections during (prolonged) rituximab therapy in rheumatoid arthritis EP - 726 SN - 1474-0338 IS - iss. 5 SP - 715 JF - Expert Opinion on Drug Safety VL - vol. 10 DO - https://doi.org/10.1517/14740338.2011.562188 ER - TY - JOUR AU - Blom, M. AU - Kievit, W. AU - Donders, A.R.T. AU - Broeder, A. den AU - Straten, V.H. AU - Kuper, I. AU - Visser, H. AU - Jansen, T.L.Th.A. AU - Brus, H.L. AU - Branten, A.J.W. AU - Laar, M.A. van der AU - Riel, P.L. van PY - 2011 UR - http://hdl.handle.net/2066/97858 AB - OBJECTIVE: To compare the effectiveness of a third tumor necrosis factor-alpha (TNF-alpha)-blocking agent with rituximab after failure of 2 TNF-blocking agents in patients with rheumatoid arthritis (RA) in daily clinical practice. METHODS: Patients receiving a third TNF-blocking agent or rituximab after failure of 2 TNF-blocking agents were selected from a Dutch biologic registry. The primary outcome was the results from the Disease Activity Score of 28 joints (DAS28) over the first 12 months after start of the third biologic using mixed-model analyses. Secondary outcomes included the course of the Health Assessment Questionnaire (HAQ) and the separate components of the DAS28 over the first 12 months and the change from baseline in DAS28 and HAQ at 3 and 6 months. RESULTS: The overall course of the DAS28 over the first 12 months was significantly better for rituximab (p = 0.0044), as also observed for the HAQ, although the latter results were not statistically significant (p = 0.0537). The erythrocyte sedimentation rates, C-reactive protein, and swollen joint counts showed a better course for rituximab (p = 0.0008, p = 0.0287, p = 0.0547, respectively), but not the tender joint counts or visual analog scale for general health. DAS28 decreased significantly in both groups at 3 and 6 months (p 65 years). Effectiveness of anti-TNFalpha therapy was primarily assessed by longitudinal analysis of the DAS28 during the first 12 months of treatment. RESULTS: Improvement in disease activity and physical functioning was significantly less in elderly patients, correcting for relevant confounders. Elderly patients reached the EULAR categories of good responders and remission less often than younger patients. Drug survival, co-medication use and tolerance were comparable between the three age groups. CONCLUSION: Anti-TNFalpha therapy significantly reduced disease activity in all age groups of patients; however, it appeared less effective in elderly compared with younger RA patients. TI - Influence of age on the outcome of antitumour necrosis factor alpha therapy in rheumatoid arthritis. EP - 1473 SN - 0003-4967 IS - iss. 9 SP - 1470 JF - Annals of the Rheumatic Diseases VL - vol. 68 DO - http://dx.doi.org/10.1136/ard.2008.094730 ER - TY - JOUR AU - Blom, M. AU - Kievit, W. AU - Fransen, J. AU - Kuper, I.H. AU - Broeder, A. den AU - Gendt, C.M. de AU - Jansen, T.L.Th.A. AU - Brus, H.L. AU - Laar, M.A. van der AU - Riel, P.L.C.M. van PY - 2009 UR - http://hdl.handle.net/2066/81197 AB - OBJECTIVE: To investigate whether the reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent influences the effect of a second TNF blocking agent. METHODS: Data were used from 2 Dutch registries including patients with rheumatoid arthritis (RA) treated with TNF blocking agents. Patients were divided into 3 groups based on reason for discontinuation of the first: nonresponse, loss of response, or adverse events. The primary outcome was the change from baseline of the disease activity (by DAS28) at 6 months, corrected for the baseline DAS28 score. Secondary outcomes were the change from baseline at 3 months, EULAR response rates, and the percentages of patients who reached a DAS28 score < or = 3.2 at 3 and at 6 months. RESULTS: In total, 49 patients who failed due to nonresponse, 75 due to loss of response, and 73 due to adverse events were included. At 6 months, the change of DAS28 score from baseline did not differ significantly between the groups (-0.6 to -1.3; p > or = 0.173) and similar good and moderate response rates were found (12% to 18%, p > or = 0.523, and 34% to 55%, p > or = 0.078, respectively). The secondary outcomes were also comparable between the 3 groups. CONCLUSION: The results of our observational study suggest that a second TNF blocking agent may be effective after failure of the first, regardless of the reason for discontinuation of the first TNF blocking agent. TI - The reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent does not influence the effect of a second TNF blocking agent in patients with rheumatoid arthritis. EP - 2177 SN - 0315-162X IS - iss. 10 SP - 2171 JF - The Journal of Rheumatology VL - vol. 36 DO - http://dx.doi.org/10.3899/jrheum.090054 ER - TY - JOUR AU - Kievit, W. AU - Fransen, J. AU - Adang, E.M.M. AU - Kuper, H.H. AU - Jansen, T.L.Th.A. AU - Gendt, C.M. de AU - Rooij, D.J. de AU - Brus, H.L. AU - Laar, M.A. van der AU - Riel, P.L.C.M. van PY - 2009 UR - http://hdl.handle.net/2066/80792 AB - OBJECTIVE: To study the adherence of rheumatologists to the Dutch guidelines for anti-tumour necrosis factor alpha (TNF-alpha) treatment. The secondary objective was to evaluate alternatives to the present guidelines with regard to the percentage of responders and costs. METHODS: The response (>1.2 DAS28 decrease) in patients who started on anti-TNF-alpha treatment for the first time was evaluated at 3 and 6 months after initiation. How many patients continued or discontinued their initial anti-TNF-alpha treatment was evaluated. Possible alternative guidelines were evaluated by means of a decision tree, with regard to the expected percentage of successfully (responders) and unsuccessfully treated patients and expected costs. RESULTS: At 3 months 56% (N = 306) and 44% (N = 233) of all 539 evaluable patients were classified as responders or non-responders, respectively. Despite the guidelines, most (81%) (N = 189) of the non-responders continued treatment. 37% of the non-responders who continued anti-TNF-alpha treatment were eventually classified as responders at 6 months. Decision analytical modelling showed that with equal expected costs all alternative strategies would result in more responders than according to theoretical full adherence with the guidelines. "Continuation in case of partial response" had the best trade-off between successfully treated patients (64%) and unsuccessfully treated patients (17%). CONCLUSION: There was suboptimal adherence to the Dutch guidelines for treatment with anti-TNF-alpha for rheumatoid arthritis patients. This seemed to be justified by the fact that a delayed response up to 6 months was shown. If treatment is continued despite a non-response at 3 months, this is only recommended in patients with at least a partial response (at least 0.6 DAS28 improvement). TI - Evaluating guidelines on continuation of anti-tumour necrosis factor treatment after 3 months: clinical effectiveness and costs of observed care and different alternative strategies. EP - 849 SN - 0003-4967 IS - iss. 6 SP - 844 JF - Annals of the Rheumatic Diseases VL - vol. 68 DO - https://doi.org/10.1136/ard.2008.094359 ER -