Combination versus monotherapy for patients with RA-are initial clinical benefits maintained over time?

BACKGROUND One-year treatment of early rheumatoid arthritis (RA) with combination therapy results in more rapid clinical improvement and less progression of joint damage than does monotherapy, but it is not known whether these benefits are maintained over a longer period. OBJECTIVE To compare the clinical and radiological benefits of combination therapy and monotherapy during 2 years' follow-up of patients with RA. DESIGN AND INTERVENTION Between April 2000 and August 2002, the randomized, controlled Behandel-Strategieen (BeSt) trial recruited patients aged ≥18 years with early RA from 18 peripheral and 2 university hospitals in the Netherlands. Other inclusion criteria included at least six swollen and six tender joints and an erythrocyte sedimentation rate ≥28 mm/h. Patients were randomly assigned to one of the following methotrexate regimens: sequential monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with sulfasalazine and tapered high-dose prednisone (group 3), or initial combination therapy with infliximab (group 4). Every 3 months, disease activity score (DAS; a continuous measure comprising the Ritchie articular index, number of swollen joints in a 44-joint count, erythrocyte sedimentation rate and global health) was evaluated, and therapy was adjusted in patients with a score >2.4 (insufficient response). Treatment was gradually withdrawn in patients who had a DAS ≤2.4 for at least 6 months, until a maintenance dosage of one drug remained. OUTCOME MEASURES The primary efficacy end point was functional ability (as determined by the Dutch Health Assessment Questionnaire [HAQ]). The primary radiographic end point was the total change in the Sharp-van der Heijde score for joint damage. RESULTS A total of 508 matched patients with a median disease duration of 23 weeks (interquartile range 14-53 weeks) were assigned to group 1 (n = 126), group 2 (n = 121), group 3 (n = 133), or group 4 (n = 128); 27 patients were lost to follow-up. Patients in groups 3 and 4 regained functional ability considerably earlier in the first year of treatment than those in groups 1 and 2, and physical function continued to improve in the second year across all groups, resulting in similar overall 2-year changes in HAQ scores (0.7, 0.8, 0.9, and 0.9, for groups 1 to 4, respectively). A mixed-model analysis found that patients in groups 3 and 4 had significantly better HAQ scores over time than those in groups 1 and 2 (P