Background The goals of treatment for rheumatoid arthritis (RA) are to reduce disease activity, reduce or arrest the rate of joint damage, and, if possible, achieve remission. The majority of the published randomised controlled trials evaluating the efficacy of disease-modifying anti-rheumatic drugs (DMARDs) are placebo (PBO)-controlled and enrol patients on background DMARDs. Driven by expectations that patients with moderate-to-severe RA randomised to PBO be quickly “rescued” with active therapy, the relative benefit of arresting joint damage with DMARDs over the long term is unclear. With longer term evidence of the rate of joint deterioration with PBO or minimal treatment, the efficacy of novel DMARDs might be projected beyond the PBO-controlled phase currently observed in clinical trials.
Objectives To estimate the joint structural deterioration over time as measured by standardised radiologic scores among minimally treated moderate-to-severe RA patients.
Methods A systematic literature review was performed to identify relevant evidence of joint structural deterioration in the following moderate-to-severe RA patient populations: 1) patients with a history of inadequate response to non-biologic DMARDs treated with one (other) non-biologic DMARD (the DMARD-IR population); and 2) patients without a history of inadequate response to a DMARD treated with non-steroidal anti-inflammatory drugs, analgesics, low-dose glucocorticoids, or one non-biologic DMARD (the non-DMARD-IR population). Outcomes of interest were the (modified) Total Sharp Score (TSS), along with its two subscales, Erosion Score (ES) and Joint Space Narrowing (JSN) score, and the Larsen score. Individual study results were synthesised by means of Bayesian meta-analysis models to obtain pooled joint structural deterioration estimates as functions of time for each of the four outcomes.
Results Forty-four studies published between 1982 and 2009 were identified. For the DMARD-IR population (nine studies) the mean change from baseline in TSS increased from 1.35 (95% credible interval 0.73; 2.06) at 12 weeks to 11.73 (6.3; 17.86) at 104 weeks when minimally treated with one non-biologic DMARD. The mean changes in ES were 0.61 (0.19; 1.13) at 12 weeks and 5.30 (1.68; 9.78) at 104 weeks; the mean changes in JSN were 0.41 (-0.31; 1.14) at 12 weeks and 3.58 (-2.72; 9.90) at 104 weeks. For the non-DMARD-IR population (35 studies), minimal treatment with one DMARD showed a non-linear increase in TSS from 1.39 (0.71; 2.06) points at 12 weeks to 4.80 (-1.04; 10.59) at 104 weeks. Corresponding mean changes in ES were 0.55 (0.24; 0.89) at 12 weeks and 2.84 (1.02; 4.70) at 104 weeks, and changes in JSN were 0.29 (0.18; 0.41) at 12 weeks and 2.52 (1.55; 3.59) at 104 weeks. For the standardised Larsen score in this non-DMARD-IR population (18 studies), the mean change from baseline was 0.08 (0.04; 0.11) at 12 weeks and 0.65 (0.36; 0.96) at 104 weeks.
Conclusions Minimal treatment of RA with one non-biologic DMARD for up to 2 years results in progressive deterioration of joint structures among patients who have shown an inadequate response to non-biologic DMARDs, as well as patients who have not (yet) shown an inadequate response to non-biologic DMARDs.
Disclosure of Interest J. Jansen Consultant for: Pfizer Inc, M. Vieira Consultant for: Pfizer Inc, J. Bradley Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Cappelleri Employee of: Pfizer Inc, S. Zwillich Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, G. Wallenstein Shareholder of: Pfizer Inc, Employee of: Pfizer Inc