Major advances have been made in the treatment of rheumatoid arthritis, a potentially chronic disabling disease which poses a large burden on both patients and society. By early start of disease... Show moreMajor advances have been made in the treatment of rheumatoid arthritis, a potentially chronic disabling disease which poses a large burden on both patients and society. By early start of disease-modifying antirheumatic drugs, including methotrexate as a prominent drug, the use of combination therapies including prednisone or biologicals, and tight control of disease activity, many patients are able to reach a state of clinical remission and some can even taper and stop antirheumatic therapy. Challenges lie in correctly identifying the earliest manifestations of the disease, starting the right treatment sufficiently early, tailored to the individual patient, and setting the optimal treatment goal at which to steer therapy adjustments. This thesis has made a start towards tackling several of these challenges and discusses further necessary steps that may lead to a fundamental change in the outlook of patients with rheumatoid arthritis. Show less
Objective: Personalized treatment depends on the treatment goals. Current prediction models to guide initial treatment choices focus on radiological damage progression. However, for some patients... Show moreObjective: Personalized treatment depends on the treatment goals. Current prediction models to guide initial treatment choices focus on radiological damage progression. However, for some patients this outcome is less relevant, whereas short-term functional ability is relevant to all. Do these various treatment goals share the same predictors? Methods: Data for 497 patients from the Dutch Behandel Strategieen (BeSt) study of treatment strategies for early rheumatoid arthritis (RA), randomized to initial monotherapy or combination therapy, were used. Predictors of short-term functional disability [Health Assessment Questionnaire (HAQ) score ≥ 1 after 3 months of treatment] were identified with logistic regression analyses. Predicted risks of a HAQ score ≥ 1 were determined for each treatment group and for each subpopulation. Results: At baseline, 76% of patients had a HAQ score ≥ 1 (mean 1.7 ± 0.5). After 3 months of treatment this score was achieved by 40% (mean HAQ score 1.5 ± 0.5). Baseline HAQ score, pain, the Ritchie Articular Index (RAI), and treatment group were significant independent predictors for a HAQ score ≥ 1; the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and baseline radiological damage were not. With cut-offs of 35% and 60%, the risk of a HAQ score ≥ 1 was high for 47% and low for 20% of the patients treated with initial monotherapy. Risks were markedly reduced in the combination therapy groups, also in unfavourable risk profiles. Conclusion: In recent-onset active RA, baseline HAQ score, pain, and initial treatment are predictors for a HAQ score ≥ 1 after 3 months. Known predictors of radiological damage were not predictive of short-term functional disability. The choice of the best initial treatment thus depends on the relevance of various outcome measures for an individual patient. Show less
The prognosis of patients with undifferentiated arthritis (UA) may vary from self-limited to severe destructive rheumatoid arthritis (RA). Based on the chance that these patients will develop RA... Show moreThe prognosis of patients with undifferentiated arthritis (UA) may vary from self-limited to severe destructive rheumatoid arthritis (RA). Based on the chance that these patients will develop RA and based on the safety profile of a course of methotrexate for 30-90 days, many clinicians consider using methotrexate in this patient category using the "n of 1" trial principle. During the last few years, more data on interventions in UA have become available that provide guidance in the prescription of drugs to UA patients. Show less
Fransen, J.; Visser, K.; Dongen, H. van; Huizinga, T.; Riel, P.L.C.M. van; Heijde, D.M. van der 2010
Objective. To study whether the Disease Activity Score (DAS) is a valid measure of disease activity in undifferentiated arthritis (UA). Methods. Data from a randomized, double-blind, placebo... Show moreObjective. To study whether the Disease Activity Score (DAS) is a valid measure of disease activity in undifferentiated arthritis (UA). Methods. Data from a randomized, double-blind, placebo-controlled trial of methotrexate (MTX) and placebo involving 110 patients with UA were used. Data included baseline and 3, 6, 9, and 12 months, as well as diagnosis at 18 months. Validity of the DAS was analyzed using factor analysis, correlations with disease activity variables, correlations with changes in disability and joint damage, differences in DAS between diagnoses, and detecting the difference between placebo and MTX. Results. Three disease activity factors were retrieved from the disease activity variables: patient reported outcomes, tender and swollen joints, and acute phase reactants. The DAS had its highest correlations (r > 0.77) with tender joint counts, followed by swollen joint counts (r > 0.63) and patient reported outcomes (r > 0.30), but the DAS correlated less with C-reactive protein levels (r = 0.32). Over time, the DAS was related to the Health Assessment Questionnaire response with an odds ratio of 4.1 (95% confidence interval 2.1-8.0), but not with change in joint damage. At 18 months, the mean DAS was 2.6 for rheumatoid arthritis patients, 2.2 for UA patients, and 1.9 for patients in remission (P = 0.001). The DAS discriminated better than all single variables between MTX and placebo, with a Guyatt's effect size of 0.89. Conclusion. The DAS appears to be a reasonably valid measure of disease activity for use in UA clinical trials. Show less
The prognosis of patients with undifferentiated arthritis (UA) may vary front self-limited to severe destructive rheumatoid arthritis (RA). Based on the chance that these patients will develop RA... Show moreThe prognosis of patients with undifferentiated arthritis (UA) may vary front self-limited to severe destructive rheumatoid arthritis (RA). Based on the chance that these patients will develop RA and based on the safety profile of a course of methotrexate for 30-90 days, many clinicians consider using methotrexate in this patient category using the "n of l" trial principle. During the last few years, more data on interventions in UA have become available that provide guidance in the prescription of drugs to UA patients. Show less
Objectives To develop a matrix model for the prediction of rapid radiographic progression (RRP) in subpopulations of patients with recent-onset rheumatoid arthritis (RA) receiving different dynamic... Show moreObjectives To develop a matrix model for the prediction of rapid radiographic progression (RRP) in subpopulations of patients with recent-onset rheumatoid arthritis (RA) receiving different dynamic treatment strategies. Methods Data from 465 patients with recent-onset RA randomised to receive initial monotherapy or combination therapy were used. Predictors for RRP (increase in Sharp-van der Heijde score >= 5 after 1 year) were identified by multivariate logistic regression analysis. For subpopulations, the estimated risk of RRP per treatment group and the number needed to treat (NNT) were visualised in a matrix. Results The presence of autoantibodies, baseline C-reactive protein (CRP) level, erosion score and treatment group were significant independent predictors of RRP in the matrix. Combination therapy was associated with a markedly reduced risk of RRP. The positive and negative predictive values of the matrix were 62% and 91%, respectively. The NNT with initial combination therapy to prevent one patient from RRP with monotherapy was in the range 2-3, 3-7 and 7-25 for patients with a high, intermediate and low predicted risk, respectively. Conclusion The matrix model visualises the risk of RRP for subpopulations of patients with recent-onset RA if treated dynamically with initial monotherapy or combination therapy. Rheumatologists might use the matrix for weighing their initial treatment choice. Show less
