Henk Visser

Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies

PURPOSE To compare the effect of delayed and early treatment strategies on disease outcome in patients with rheumatoid arthritis. SUBJECTS AND METHODS Between 1993 and 1995, 109 patients diagnosed with probable or definite rheumatoid arthritis of recent onset were initially treated with analgesics; if they had persistent active disease, they were treated subsequently with the disease-modifying drugs chloroquine or salazopyrine (delayed treatment). Between 1996 and 1998, similar patients (n = 97) were promptly treated with either chloroquine or salazopyrine (early treatment). RESULTS The median lag to the initiation of disease-modifying treatment was 15 days in the early treatment group and 123 days in the delayed treatment group. There was less radiologic joint damage after 2 years in the early treatment group (median Sharp score, 3.5; 95% confidence interval [CI]: 1 to 7) compared with the delayed treatment group (median Sharp score, 10; 95% CI: 5 to 15; P <0.05). The median area under the curve of the 2-year disease activity score was lower in the early treatment group (64 units; 95% CI: 59 to 69 units) compared with the delayed treatment group (73 units; 95% CI: 69 to 77 units; P = 0.002). CONCLUSION In this nonrandomized comparison, early introduction of disease-modifying antirheumatic drugs was associated with a better disease outcome after 2 years.

HLA-DQ-associated predisposition to and dominant HLA-DR-associated protection against rheumatoid arthritis

We have recently proposed a new hypothesis to explain the association of Human Leukocyte Antigen (HLA) with rheumatoid arthritis (RA) predisposition. In this model, which challenges the Shared Epitope (SE) hypothesis, HLA-DQ predisposes while HLA-DR protects. In the present study, we have compared these two models in an Early Arthritis Clinic started in 1993 in the Department of Rheumatology at the Leiden University Medical Centre. Out of 524 patients who enrolled this programme in the period 1993-1998 and completed the one year follow-up, 155 have been classified as RA. These patients along with 306 consecutive cadaveric renal organ donors have been typed for HLA-DR and -DQ. The distributions of predisposing DR alleles according to SE, and predisposing DQ and protective DR according to our model were analysed. We found that two doses of predisposing DQ alleles strongly predisposed to RA, even in individuals with a single dose of SE while DRB1 alleles carrying the motif DERAA confered a dominant protection in DQ5-positive individuals. We conclude that the present findings are consistent with our previously described model of HLA and RA association. Using this new model, we have been able to characterise two novel groups of individuals on the basis of their HLA typing: one strongly predisposed to RA and one protected. Knowing the mechanism of HLA-related dominant natural protection may help in designing novel treatment modalities for RA.

Tapering and discontinuation of methotrexate in patients with RA treated with TNF inhibitors: data from the DREAM registry.

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.

Tailored, Therapist-Guided Internet-Based Cognitive Behavioral Therapy Compared to Care as Usual for Patients With Rheumatoid Arthritis: Economic Evaluation of a Randomized Controlled Trial

Background Internet-based cognitive behavioral therapy can aid patients with rheumatoid arthritis with elevated levels of distress to enhance their quality of life. However, implementation is currently lacking and there is little evidence available on the (cost-) effectiveness of different treatment strategies. Objective Cost-benefit ratios are necessary for informing stakeholders and motivating them to implement effective treatment strategies for improving health-related quality of life (HRQoL) of patients with rheumatoid arthritis. A cost-effectiveness study from a societal perspective was conducted alongside a randomized controlled trial on a tailored, therapist-guided internet-based cognitive behavioral therapy (ICBT) intervention for patients with rheumatoid arthritis with elevated levels of distress as an addition to care as usual (CAU). Methods Data were collected at baseline or preintervention, 6 months or postintervention, and every 3 months thereafter during the 1-year follow-up. Effects were measured in terms of quality-adjusted life years (QALYs) and costs from a societal perspective, including health care sector costs (health care use, medication, and intervention costs), patient travel costs for health care use, and costs associated with loss of labor. Results The intervention improved the quality of life compared with only CAU (Δ QALYs=0.059), but at a higher cost (Δ=€4211). However, this increased cost substantially reduced when medication costs were left out of the equation (Δ=€1863). Of all, 93% (930/1000) of the simulated incremental cost-effectiveness ratios were in the north-east quadrant, indicating a high probability that the intervention was effective in improving HRQoL, but at a greater monetary cost for society compared with only CAU. Conclusions A tailored and guided ICBT intervention as an addition to CAU for patients with rheumatoid arthritis with elevated levels of distress was effective in improving quality of life. Consequently, implementation of ICBT into standard health care for patients with rheumatoid arthritis is recommended. However, further studies on cost reductions in this population are warranted. Trial Registration Nederlands Trial Register NTR2100; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2100 (Archived by WebCite at http://www.webcitation.org/724t9pvr2)