Background/Purpose: To evaluate possible differences in clinical response after one year of remission steered treatment in Anti Citrullinated Protein Antibody (ACPA) positive and negative RA and UA patients in the IMPROVED study.  

Methods: IMPROVED is a multicenter trial in 479 rheumatoid arthritis (RA, 2010 criteria, symptoms <2 years) and 122 undifferentiated arthritis (UA) patients with a baseline Disease Activity Score (DAS) ≥1.6. All patients started with methotrexate (MTX) and a tapered high dose of prednisone. Patients in early remission (DAS<1.6 at t=4 months) tapered prednisone to zero and when still in remission at t=8 months, also tapered MTX to zero. Patients not in early remission were randomized to a combination of MTX, hydroxychloroquine (HCQ), sulphasalazine (SSZ) and low dose prednisone (arm 1) or to adalimumab (ADA) with MTX (arm 2). If not in remission at t=8 months, arm 1 switched to ADA+MTX and arm 2 increased ADA. Proportions remission after one year were compared between ACPApos and ACPAneg UA and RA patients.

Results: Of the UA patients, 111 (91%) were ACPApos and 4 (3%) ACPAneg (data not shown), of the RA patients 324 (68%) were ACPApos and 148 (31%) ACPAneg. Twenty-three patients had missing data. ACPAneg UA patients had a lower baseline DAS compared to ACPAneg and ACPApos RA. Both ACPAneg RA and UA patients had a shorter symptom duration than ACPApos RA patients (table). Early remission was achieved less often in ACPAneg RA patients compared to ACPAneg UA and ACPApos RA patients. After 1 year, similar proportions in ACPApos and ACPAneg RA and UA patients achieved remission. Patients in early remission most often were in remission after one year regardless of ACPA status or classification. ACPApos patients in arm 2 more often achieved remission after 1 year than ACPApos patients in arm 1 (18 (51%) vs 10 (25%), p=0.01). A similar trend was seen for ACPAneg patients (table). Independent predictors for achieving remission after 1 year are male sex, low baseline DAS and achieving early remission. ACPA status was not predictive for remission after one year.

Conclusion: In the IMPROVED trial remission after 1 year is achieved in similar proportions of patients with early arthritis, regardless of ACPA status or classification. A low baseline DAS and achieving early remission after initial treatment with prednisone and methotrexate is predictive for achieving remission after one year. Of those not achieving early remission, ACPApos RA, and probably ACPAneg UA and RA patients, benefit more from a treatment strategy with adalimumab than of one with multiple DMARDs with low dose prednisone.

Table: Baseline characteristics and proportions remission after one year of ACPA positive and negative UA and RA patients.