Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial

Abstract

Background: Sarilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-6 receptor complex. In the MOBILITY phase III randomized controlled trial (RCT), sarilumab + methotrexate (MTX) treatment resulted in clinical improvements at 24 weeks that were maintained at 52 weeks in adults with rheumatoid arthritis (RA), who have inadequate response to MTX (MTX-IR). These analyses indicate the effects of sarilumab + MTX versus placebo on patient-reported outcomes (PROs) in this RCT.

Methods: Patients (n = 1197) were randomized to receive placebo, sarilumab 150 or 200 mg subcutaneously + MTX every 2 weeks for 52 weeks; after 16 weeks, patients without ≥20 % improvement from baseline in swollen or tender joint counts on two consecutive assessments were offered open-label treatment. PROs included patient global assessment of disease activity (PtGA), pain, health assessment questionnaire disability index (HAQ-DI), Short Form-36 Health Survey (SF-36), and functional assessment of chronic illness therapy-fatigue (FACIT-F). Changes from baseline at weeks 24 and 52 were analyzed using a mixed model for repeated measures. Post hoc analyses included percentages of patients reporting improvements equal to or greater than minimal clinically important differences (MCID) and normative values in the FACIT-F and SF-36. Pearson correlation between observed PRO scores and clinical measures of disease activity was tested at week 24.

Results: Both doses of sarilumab + MTX vs placebo + MTX resulted in improvement from baseline by week 24 in PtGA, pain, HAQ-DI, SF-36 and FACIT-F scores (p < 0.0001) that was clinically meaningful, and persisted until week 52. In post hoc analyses, the percentages of patients with improvement equal to or greater than the MCID across all PROs were greater with sarilumab than placebo (p < 0.05), with differences ranging from 11.6 to 26.2 %, as were those reporting equal to or greater than normative scores.

Conclusions: In this RCT in patients with MTX-IR RA, sarilumab + MTX resulted in sustained improvement in PROs that were clinically meaningful, greater than placebo + MTX, and complement the previously reported clinical efficacy and safety of sarilumab.

Trial registration: ClinicalTrials.gov. NCT01061736 . February 2, 2010.

Keywords: Fatigue; Interleukin-6; Patient-reported outcomes; Rheumatoid arthritis; Sarilumab.

Fig. 1

Mean scores at each visit through week 24 for a patient’s global assessment of disease activity, b pain, c physical function, and d fatigue. Broken vertical line indicates the earliest opportunity for rescue medication; patients who did not achieve ≥20 % improvement from baseline in swollen or tender joint count on two consecutive assessments were offered rescue therapy with open-label sarilumab 200 mg every 2 weeks. HAQ-DI health assessment, FACIT-F functional assessment of chronic illness therapy-fatigue questionnaire disability index, MTX methotrexate

Fig. 2

Combined baseline (BL) and post-treatment scores at week 24 across all Short Form 36 (SF-36) domains relative to age-adjusted and gender-adjusted norms (A/G matched norms) for the US general population. All scores on a 0–100 scale (0 = worst, 100 = best). PF physical functioning, RP role physical, BP body pain, GH general health, VT vitality, SF social functioning, RE role emotional, MH mental health. Note, as combined baseline scores are presented, change from baseline for each cohort cannot be inferred from Fig. 2 alone

Fig. 3

Responder analyses for patients with improvement equal to or greater than the minimal clinically important difference (MCID). a Differences from placebo in the percentage of patients reporting improvement equal to or greater than the MCID after 24 weeks of treatment according to patient global assessment (PtGA), pain, functional assessment of chronic illness therapy-fatigue (FACIT-F), health assessment questionnaire-disability index (HAQ-DI), and the Short Form 36 (SF-36) physical and mental component scores. b Differences from placebo in the percentage of patients reporting improvements equal to or greater than the MCID after 24 weeks of treatment in SF-36 domain scores. PF physical functioning, RP role physical, BP body pain, GH general health, VT vitality, SF social functioning, RE role emotional, MH mental health, NNT number needed to treat for sarilumab + methotrexate (MTX) versus placebo + MTX

Fig. 4

Responder analyses for normative scores and patient acceptable symptom state (PASS). a Percentage of patients reporting scores equal to or greater than normative values on the functional assessment of chronic illness therapy-fatigue (FACIT-F) and Short Form 36 (SF-36) at baseline. b Percentage of patients reporting scores equal to or greater than PASS thresholds at baseline. c Percentage of patients reporting scores equal to or greater than normative values on the FACIT-F and SF-36 at week 24. d Percentage of patients reporting scores equal to or greater than PASS thresholds at week 24. PF physical functioning, RP role physical, BP body pain, GH general health, VT vitality, SF social functioning, RE role emotional, MH mental health

Fig. 5

Correlation between observed patient-reported outcomes and disease activity scores at Week 24