The CIMESTRA study: intra-articular glucocorticosteroids and synthetic DMARDs in a treat-to-target strategy in early rheumatoid arhtritis.
OBJECTIVES
Treatment of early rheumatoid arthritis (RA) include aiming at disease control with early use of methotrexate (MTX) in monotherapy or in combination with glucocorticoids or other disease-modifying drugs (DMARDs). The CIMESTRA study applied an aggressive treatment with DMARD and intra-articular injections of glucocorticoids (i.a. GC) to control disease activity. This paper reviews the results of the five years' study.


METHODS
160 patients with early RA (<6 months duration) were randomized to receive MTX 7.5-20 mg/week+cyclosporine (CYA) 2.5-4 mg/kg (combination) or MTX+placebo-CYA (monotherapy). At each visit (week 0, 2, 4, 6, 8, thereafter monthly up to 24 months) patients had steroid injections in all swollen joints. During year 2, CYA/placebo was withdrawn, and hydroxychlorochine added. Clinical responses were assessed by ACR20, 50 and 70, ACR and DAS remission. Radiographic progression by x-rays of hands and feet.


RESULTS
At year 1 (year 5) treatment responses in mono/combination groups were: ACR20: 68% (85%) / 85% (94%), ACR50: 53% (74%) / 68% (88%), ACR70: 44% (63%) / 59% (72%). After year 1, no significant differences between groups were found. Remission rates were: ACR-remission: 28% (52%) / 35% (60%), DAS28-remission: 34% (76%) / 43% (80%). Radiographic progression in both groups was <1TSS unit/year. After 1 and 2 years, 62% and 56% of the injected joints had not relapsed (both groups). Cumulated i.a.GC dose <1mg prednisolone/day. 19% received biologics by 5 years, 16% no treatment (sustained ACR-remission). Baseline magnetic resonance imaging (MRI) bone oedema best predicted radiographic progression after 2 years. Treatments were well tolerated.


CONCLUSIONS
MTX and i.a.GC in a treat-to-target strategy over 5 years halted radiographic progression and induced remission in the majority of patients. I.a. GC had in long-lasting effect and cumulated dosages were low.