Slow progression of joint damage in early rheumatoid arthritis treated with cyclosporin a

Abstract

Objective. To evaluate the ability of low‐dose cyclosporin A (CsA) to control radiologic disease progression, and to assess the clinical efficacy and tolerability of CsA, compared with conventional disease‐modifying antirheumatic drugs (DMARDs), in patients with early active rheumatoid arthritis (RA). Methods. In this long‐term, multicenter, prospective, open, blinded end point, randomized trial, 361 consenting patients with early (< 4 years since diagnosis) active RA were enrolled. Of the eligible patients, 167 were treated with CsA at 3 mg/kg/day, and 173 with DMARDs. The decision to use conventional antirheumatic drugs as controls was based on the fact that joint erosion could be expected to occur after 1 year regardless of the type of DMARD being used. The possibility of switching therapies in both groups was intended to keep the largest possible number of patients in the study. Results. Blinded evaluation of hand and foot radiographs after 12 months of treatment showed that CsA led to a significant (P < 0.001) delay in the mean ± SD progression in the eroded joint count (1.3 ± 3.1 versus 2.4 ± 3.0 for the control group) and in the joint damage score (3.6 ± 8.9 versus 6.9 ± 9.1 for the control group), both measured by the Larsen‐Dale method. When only the patients without erosion at baseline were considered (37 in the CsA‐treated group and 54 in the control group), erosion appeared in only 10.8% of the CsA‐treated patients, but in 51.8% of the controls (P = 0.00005). Low‐dose CsA was as effective as traditional DMARDs in controlling clinical symptoms. Maintenance on the initially prescribed treatment regimen (“survival on treatment”) was also better at 12 months with CsA than with DMARDs (89.2% versus 77.5%; P = 0.002). The tolerability of CsA was acceptable. Conclusion. These 12‐month results suggest that low‐dose CsA decreases the rate of further joint damage in previously involved joints as well as the rate of new joint involvement in previously uninvolved joints, in patients with early RA.

High Levels of IL-17 in Rheumatoid Arthritis Patients: IL-15 Triggers In Vitro IL-17 Production Via Cyclosporin A-Sensitive Mechanism

“…Consequently, these doses are currently recommended for RA treatment. Low concentrations of CsA that effectively block IL-17 production in vitro are even below the range of concentrations of this drug observed in patients with RA (22,23). Therefore, it is likely that in in vivo situation, the concentration of CsA, although low, is still high enough to prevent the induction of IL-17 production.…”

Classifying structural joint damage in rheumatoid arthritis as progressive or nonprogressive using a composite definition of joint radiographic change: A preliminary proposal

“…By inspection, the composite definitions 4,5,12,15,16,17,18,20, and 22 were selected for further evaluation. With definitions 4, 5, and 17, more than 90% of patients with progression in the total Sharp score at or below the median were categorized as having nonprogressive joint damage, and more than 75% of patients with more than median progression were categorized as having progressive joint damage (Table 2).…”

“…It is only after relentless progression of chronic RA for 10 or 15 years or longer that cumulative radiographic damage reaches the threshold of major disability and surgical repair. However, if treatment is delayed until the functional consequences of cumulative radiographic damage are obvious, then the damage cannot be undone; rather, the damage must be prevented before it occurs, which is the basis for the current interest in medications that prevent or slow the progression of damage (7)(8)(9)(10)(11)(12)(15)(16)(17)(18)(19)(20)(21).…”

“…421.4 (13) 382.0 (9) 406.6 (16) 401.7 (6) 425.5 (15) 361.9 (7) 425.5 (15) 361.9 (7) 462.3 (12) 336.9 (10) Two year followup, % ever ACR20 2 ϭ decrease (see Table 1 for definitions of nonprogression). † P Ͻ 0.005 versus not progressive.…”

“…Controlled clinical trials of 6 or 12 months' duration have documented that the progression of radiographic damage scores was more rapid in the placebo group than in groups that received methotrexate (MTX) (8), leflunomide (8), sulfasalazine (SSZ) (8), prednisolone (9,10), interleukin-1 receptor antagonist (11), or an infliximab/MTX combination (12), and that radiographic progression following treatment with etanercept was less rapid than that following treatment with MTX (13). Other studies have evaluated radiographic progression in patients treated with corticosteroids (14,15), cyclosporin A (16,17), MTX versus azathioprine (18), MTX versus auranofin (19), MTX (meta-analysis) (20), hydroxychloroquine (HCQ) versus SSZ (21), SSZ (22), the COBRA (Combinatietherapie Bij Reumatoïde Artritis) combination of prednisolone, MTX, and SSZ (23,24), combinations of MTX, SSZ, and HCQ (25,26), the combination of cyclophosphamide, azathioprine, and HCQ (27), and the combination of adalimumab with MTX (28).…”