RA and Work Loss: Biologic versus DMARD Treatment

The introduction of biologic tumor necrosis factor inhibitors has improved the treatment of early rheumatoid arthritis (RA), but at a significant cost. These medications have been shown to lead to superior radiological outcomes compared with a combination of conventional disease-modifying antirheumatic drugs (DMARDs) over 2 years. Using follow-up data from the Swefot (Swedish Pharmacotherapy) trial that compared the effect of biologic versus combination treatment, researchers investigated whether radiological superiority translates into better work loss outcomes. The results found that biologic therapy was not superior to conventional treatment on work loss >21 months in patients with RA who had experienced an insufficient response to methotrexate [JAMA Intern Med. 2013;173(15):1407-1414].

Swefot was a multicenter, 2-arm, parallel, randomized, active-controlled, open-label trial that included adult patients ≥18 years of age with RA symptoms <1 year, no previous treatment with DMARDs, no oral or stable glucocorticoid therapy for at least 4 weeks, and a disease activity score based on a 28-joint count disease activity score of >3.2. Patients who did not achieve low disease activity after 3 to 4 months of receiving methotrexate therapy were randomized to receive add-on biologic treatment with infliximab or conventional combination treatment with sulfasalazine plus hydroxychloroquine. The primary end point was work loss measured as monthly days with sick leave and disability pension compensation (maximum, 30 days/month), using data from the Swedish Social Insurance Agency.

A total of 493 patients were recruited from 15 rheumatology units in Sweden from October 1, 2002, through December 31, 2005, with 487 patients enrolled in the study. Of the 204 eligible patients, 105 were randomized to infliximab and 99 to conventional treatment. Seven patients in the infliximab treatment arm and 4 in the conventional treatment arm never received the study drug, and 72 and 52 patients, respectively, followed the study protocol for 2 years. The study population was restricted to working age patients (<63 years of age). The baseline average work loss was 17 days per month (median 16 days/month) in both treatment groups (mean difference, 0.6 days/month; 95% confidence interval [CI], −3.0 to 3.9). Greater work loss was seen with older age (age 19-44, 14 days/month; age 45-54, 18 days/month; age ≥55, 19 days/month; P=.048).

The average changes in work loss at 21 months were −4.9 days per month in the biologic treatment group and −6.2 days per month in the conventional treatment group (adjusted mean difference, 1.6 days/month; 95% CI, −1.2 to 4.4). Including patients receiving at least 1 dose of assigned treatment, the adjusted mean difference was 1.5 days per month (95% CI, −1.5 to 4.4), and in per-protocol analysis, the adjusted mean difference was 0.3 days per month (95% CI, −2.8 to 3.8).

The investigators noted 2 study limitations: (1) patients and physicians were aware of the treatment allocation because infliximab is administered via infusion and conventional combination treatment is given orally; and (2) the restriction to working age patients may have affected the random allocation.

“Our analysis showed that early and aggressive treatment in methotrexate-resistant patients not only stops the trend of increasing work loss days, as in patients with mainly established RA, but partly reverses it,” concluded the researchers. “However, we did not find any difference between treatment arms, indicating that the significantly improved disease control associated with infliximab treatment over a 1-year period and the radiological results after 2 years did not translate into less work loss.”

They noted that the significantly higher cost of infliximab treatment relative to conventional treatment needs to be considered against the greater rate of short-term adverse events leading to treatment discontinuation with conventional treatment.