Early RA: Work Loss Same With Biologicals, DMARD Combo Tx

Janis C. Kelly

July 08, 2013

Two-year follow-up data in early rheumatoid arthritis (RA) from one of the few randomized controlled trials to compare the effect of biological vs conventional combination treatment on work loss found that biological therapy was not superior, according to a report published online July 1 in JAMA Internal Medicine.

Lead researcher Jonas K. Eriksson, MSc, a PhD student at the Karolinska Institute Unit of Clinical Epidemiology, Stockholm, Sweden, told Medscape Medical News that the research team was somewhat surprised by the results.

"In the Swedish Farmacotherapy (Sefot) trial, patients in the biologic treatment group had improved clinical outcomes after 1 year and better radiographical results after 2 years compared to patients randomized to the conventional treatment group. For this reason, the finding of no difference in work loss change at 21 months between the treatment groups was somewhat unexpected. With work loss as an outcome, which may be more inert to treatment than clinical and radiological outcomes, longer follow-up may be desirable," Eriksson said.

In this study, the researchers examined work loss for patients in the Sefot trial. The trial included adult patients with RA symptom duration of less than 1 year, no previous disease-modifying antirheumatic drug (DMARD) treatment, no oral or stable glucocorticoid therapy, and a disease activity score based on a 28-joint count of more than 3.2. Patients who did not achieve adequate disease control after 3 to 4 months of receiving methotrexate were randomly assigned (open label) to receive add-on biological treatment with infliximab (n = 105) or conventional combination treatment with sulfasalazine plus hydroxychloroquine (n = 99). Work loss was measured as monthly days with sick leave and disability pension compensation (maximum, 30 days/month), using data on sick leave and disability pensions from the Swedish Social Insurance Agency.

The researchers found that the baseline average work loss was 17 days per month in both groups. The average changes in work loss at 21 months were −4.9 days per month in the biological and −6.2 days per month in the conventional treatment group, a difference that was not statistically significant.

"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. 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 better radiological results after 2 years did not translate into less work loss," the authors note.

"The substantially higher cost of infliximab relative to conventional treatment needs to be weighed against the greater incidence of short-term adverse events leading to discontinuation of conventional treatment," they conclude.

"These findings suggest not only that suppression of disease activity is an important predictor of work loss but that other factors such as psychosocial and job-related factors may also play a role," Suzanne Verstappen, MD, told Medscape Medical News. "It is known that patients in manual jobs are more likely to become work-disabled and report sick leave. Unfortunately, job type was not recorded in this study. Also, other job-related contextual factors or personal contextual factors may play a role. During the [European League Against Rheumatism 2013 conference] in Madrid, 2 presentations also showed an association between depression/anxiety and sick leave. The focus of preventing sick leave/work loss should therefore not only be suppression of disease activity very early in the disease but also evaluation of working situation and psychosocial factors." Dr. Verstappen, who was not involved in this study, is a research fellow at the Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, United Kingdom.

"In general, the main therapy aim in early RA should be early and aggressive treatment, but it may not be necessary to start with a biological in every patient. In those patients who respond well to monotherapy [methotrexate] or [conventional] combination treatment, it is probably not cost-effective to start with a biologic treatment as first therapy. It is, however, important to identify those patients who are most likely to be nonresponders to conventional DMARDs as soon as possible and to fast-track these patients onto biologics, as the study by Eriksson et al shows that already in the first few months after symptom onset, work loss is considerable, and most patients on disability pension do not return to work," Dr. Verstappen said.

In an invited commentary, Edward Yelin, PhD, from the University of California, San Francisco, writes, "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 the fine study done by Eriksson and colleagues indicates that it may be good enough."

The study was funded by the Swedish Rheumatism Association and Schering-Plough/Merck Sharp and Dohme. One coauthor has reported receiving research support and honoraria from Abbott, GlaxoSmithKline/Human Genome Sciences, Merck Sharp and Dohme, Pfizer, Roche, and Union Chimique Belge Pharma. One coauthor reported participating in advisory boards for Pfizer and Abbott; participating in research projects fully or partly funded by Schering-Plough, AstraZeneca, Novo Nordisk, Pfizer, or Roche; and serving as an external consultant to Pfizer, sanofi-aventis, and Abbott. Dr. Yelin has reported receiving support from Amgen (formerly Immunex) from 1998 through 2004 for a study of long-term outcomes of etanercept and from Aspreva from 2005 through 2008 for a study of long-term outcomes in persons with systemic lupus erythematosus who participated in mycophenolate mofetil trials. The other authors and Dr. Verstappen have disclosed no relevant financial relationships.

JAMA Intern Med. Published online July 1, 2013. Article abstract, Commentary extract

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