Clinical and Radiological Outcomes of 5 Years Remission Steered Treatment in Early Rheumatoid and Undifferentiated Arthritis Patients

BACKGROUND/PURPOSE:

To assess clinical and radiological outcomes of induction therapy followed by 5 years disease activity score (DAS)-remission steered treatment in early arthritis patients.

METHODS:

The IMPROVED study enrolled 610 early rheumatoid arthritis (RA, 2010) or undifferentiated arthritis (UA) patients. All started induction therapy methotrexate (MTX) and tapered high dose of prednisone. If DAS-remission (<1.6) was achieved at 4 months prednisone was stopped (early DAS-remission (ER)) and if remission persisted at 8 months MTX was also stopped. Patients not in ER were randomized to MTX+sulfasalazine+hydroxychloroquine+low dose prednisone (arm 1) or MTX+adalimumab (arm 2), 50 patients were not randomized and were treated ‘outside of protocol’ (OP). Every 4 months treatment adjustments aimed at DAS<1.6: DAS<1.6 taper/stop medication and DAS≥1.6 restart/intensify. (Drug-free) DAS-remission percentages were compared between the different diagnosis and treatment strategies. Radiologic damage progression (Sharp-vanderHeijde Score, SHS) from baseline to 5 years was scored by 2 independent readers in chronologic order.

RESULTS:

Patients in the ER group had better functional ability over time, compared to arms 1 and 2 and the OP group, who between them had similar HAQ scores over time (figure). 295/610 (48%) patients achieved DAS-remission at 5 years: 220/387 (57%) in the ER group, 31/83 (37%) in arm 1, 29/78 (37%) in arm 2 (p=0.768 arm 1 vs arm 2) and 15/50 (30%) in OP (figure). 134/610 (22%) patients achieved DFR (drug-free DAS-remission): 105/387 (27%) in the ER group, 9/83 (11%) in arm 1, 12/78 (15%) in arm 2 (p=0.374 arm 1 vs arm 2) and 8/50 (16%) in OP (figure). DAS-remission percentages were similar in RA and UA patients and autoantibody positive (+) vs negative (‒) patients. More UA patients achieved DFR (33% UA vs 19% RA, p<0.001), and more patients negative for anti-citrullinated protein antibodies (ACPA) (31% ACPAneg vs 15% ACPApos, p<0.001) or rheumatoid factor (RF) (28% RFneg vs 17% RFpos, p<0.001) achieved DFR. Median (IQR) SHS progression was 0.5 (0-3) in 306 completers in the ER group, 0 (0-1) in arm 1 (62 completers), 0 (0-1) in arm 2 (59 completers) (p=0.818 arm 1 vs arm 2) and 0 (0-3) in 31 OP completers. SHS progression ≥5 points had occurred in 40/306 (13%) in the ER group, 9/62 (15%) in arm 1, 7/59 (12%) in arm 2 (p=0.710 arm 1 vs arm 2) and 2/31 (6%).

CONCLUSION:

Induction therapy followed by 5 years DAS-remission steered treatment resulted in 48% DAS-remission and 22% DFR in early RA and UA patients. More UA patients and more autoantibody negative patients achieved DFR. Radiologic damage progression was well suppressed in the majority of patients.