Biological compared with conventional treatment may not improve work loss in early rheumatoid arthritis

Infliximab improved radiologic results but did not result in less work loss compared with conventional combination therapy in patients with early rheumatoid arthritis who did not respond sufficiently to methotrexate, a new study reports.

Researchers analyzed data from a parallel, randomized open-label trial of patients from 15 rheumatology clinics in Sweden who were randomly assigned to receive additional treatment with infliximab or conventional combination treatment with sulfasalazine and hydroxychloroquine after three to four months of unsuccessful treatment with methotrexate. Patients were included if they were of working age (<63 years), had been diagnosed with rheumatoid arthritis according to revised American College of Rheumatology criteria, had not previously been treated with disease-modifying antirheumatic drugs (DMARDs), had not received oral or stable glucocorticoid therapy for at least four weeks, and had a disease activity score above 3.2 on a 28-joint count scale.

The infliximab group received infliximab, 3 mg per kg of body weight, at 0, 2 and 6 weeks and then every 8 weeks. The conventional treatment group received 1,000 mg of oral sulfasalazine twice daily and 400 mg of oral hydroxychloroquine daily. Main outcome measures were monthly sick leave and disability pension days 21 months after randomization. The study results were published online July 1 by JAMA Internal Medicine.

Two hundred four patients were eligible for randomization. Of these, 105 were randomly assigned to biological treatment and 99 were assigned to conventional treatment. The study drug was never administered to seven patients in the biological group or to four patients in the conventional treatment group. A total of 124 patients, 72 in the biological group and 52 in the conventional treatment group, followed the study protocol for 21 months. At baseline, the mean work loss in both groups was 17 days per month. At 21 months, the mean changes in work loss were −4.9 days per month in the biological group and −6.2 days in the conventional group, an adjusted mean difference of 1.6 days per month. When the authors looked only at patients who received at least one dose of the assigned treatment, the adjusted mean difference was 1.5 days per month; in per protocol analysis, it was 0.3 day per month.

The authors noted that their study was not blinded and that it included only patients who were of working age. However, they concluded that although biological treatment yields superior findings on radiographic assessments, it did not differ from conventional combination treatment in terms of work loss. “Treatment including a biological agent was not superior to conventional treatment in terms of effect on work loss over a 21-month period in patients with early [rheumatoid arthritis] with methotrexate treatment failure,” the authors wrote. “Although a substantial improvement in work loss was achieved in both arms, the persisting gap relative to the general population indicates a need for more effective treatment strategies and earlier diagnosis of [rheumatoid arthritis].”

The author of an accompanying editorial pointed out that both treatment regimens, those that included biological agents and those that did not, substantially reduced the number of work days lost. “In the real world, in which payers approve biological agents only for patients in whom conventional DMARDs have failed, the true implication of the current findings may be that biological combination treatments may have an acceptable employment outcome even when initiated after conventional DMARDs have proved insufficient,” the editorialist wrote. “In the real-world situation of sequential use of combinations, first excluding and only after that including biological agents, the outcome might not match that achieved after simultaneous randomization, but [this] fine study…indicates that it may be good enough.”