TARGET Trial: Sarilumab Improves PROs in Rheumatoid Arthritis

A recently published study demonstrates that sarilumab improves patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) who did not achieve adequate response with, or who were intolerant to, anti-tumor necrosis factor (anti-TNF) agents.

Vibeke Strand, MD, and her coauthors, in a study sponsored by Sanofi and Regeneron, evaluated the effects of the monoclonal antibody administered together with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) based on PROs in the TARGET trial.

The authors note that PROs are important supplemental endpoints that can help in evaluating responses to treatment for RA. While clinical measures of RA, including the American College of Rheumatology (ACR) response criteria, include PROs, such measures rarely assess fatigue, ability to work, health-related quality of life, or health status.

In the TARGET trial, which included the assessment of PROs, 546 adults with moderate to severe RA who did not respond adequately to, or did not tolerate, anti-TNF treatments were randomized to receive placebo, 150 mg of sarilumab, or 200 mg of sarilumab every 2 weeks together with csDMARDs. The PROs addressed in the study included measures of pain, fatigue, function, participation, and health status. The methods used to assess these areas included:

• Patient global assessment
• Pain and morning stiffness visual analogue scales
• Health assessment questionnaire disability index
• Short form 36 health survey (which assesses physical function, physical role function, bodily pain, general health perceptions, vitality, social functioning, emotional role function, and mental health)
• Functional assessment of chronic illness therapy-fatigue
• Work productivity survey-RA (which assesses employment status; absenteeism; presenteeism; rate of RA interference with work in and outside the home; and participation in social, family, and leisure activities)
• RA impact of disease (which measures pain, functional disability, fatigue, physical and emotional wellbeing, quality of sleep, and coping)

Changes from baseline at weeks 12 and 24 were analyzed using a mixed model for repeated measures that tested the least square mean (LSM) changes from baseline, between each active treatment group and the placebo group, at weeks 12 and 24. Post hoc analyses included percentages of patients who reported improvements greater than or equal to minimum clinically important differences and scores greater than or equal to normative values.

Sarilumab in both doses, in combination with csDMARDs, resulted in greater improvements from baseline versus placebo together with csDMARDs:

• LSM changes from baseline in patient global assessment and pain were greater with sarilumab in both doses than with placebo at weeks 12 and 24
• Statistically significant improvements in change from baseline in the health assessment questionnaire disability index were reported in patients receiving both doses of sarilumab at weeks 12 (P<.001) and 24 (P<.05)
• Greater improvement was demonstrated with both sarilumab doses versus placebo at week 12 in the functional assessment of chronic illness therapy-fatigue, morning stiffness, and short form 36 health survey
• Improvements were reported across all short form 36 health survey areas at weeks 12 and 24, and were greater with sarilumab than with placebo (with the exception of general health perceptions, emotional role function, and mental health in the 150-mg group in weeks 12 and 24, and emotional role function in the 200-mg group at week 24.)

Among patients who were employed outside the home:

• Patients reported greater reduction in lost days of productivity with the 200-mg dose of sarilumab versus the placebo (−3.2 days vs −2.0 days; P<.05)
• Patients reported greater reductions in the rate of RA interference with work productivity (on a scale in which 0 = no interference, and 10 = total interference) versus the placebo in the 200-mg dose (−2.7 vs −1.6; P<.05)
• The groups receiving both doses of sarilumab reported greater reductions versus the placebo in missed work days within the home, days on which outside help was required, the rate of RA interference with household work, and days of missed activities.

The researchers concluded that, in patients for whom treatment with anti-TNF agents was inadequate or not tolerated, 150-mg and 200-mg doses of sarilumab, given together with csDMARDs, resulted in clinically meaningful patient-reported benefits in terms of pain, fatigue, function, participation, and health status at week 12 and week 24, and that mean changes from baseline translated into clinically meaningful benefits on an individual patient level.

Strand, during a recent Peer Exchange™ panel discussion at The Center for Biosimilars^®, said, “In general, I think we’re learning a lot more about the biologic products, and that translates also into learning how we might have better precision medicine—how there might be individual variability and what the appropriate therapy is for a patient. We’re still just cracking that nut, but I think it’s one of the things to look forward to.”