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. 2017 Mar 7;3(1):e000416.
doi: 10.1136/rmdopen-2016-000416. eCollection 2017.

Sarilumab improves patient-reported outcomes in rheumatoid arthritis patients with inadequate response/intolerance to tumour necrosis factor inhibitors

Vibeke Strand  1 , Matthew Reaney  2 , Chieh-I Chen  3 , Clare W J Proudfoot  2 , Sophie Guillonneau  4 , Deborah Bauer  5 , Erin Mangan  3 , Neil M H Graham  3 , Hubert van Hoogstraten  5 , Yong Lin  5 , César Pacheco-Tena  6 , Roy Fleischmann  7
Affiliations

Sarilumab improves patient-reported outcomes in rheumatoid arthritis patients with inadequate response/intolerance to tumour necrosis factor inhibitors

Vibeke Strand et al. RMD Open. .

Abstract

Objective: To evaluate effects of the anti-interleukin-6 receptor monoclonal antibody sarilumab administered with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on patient-reported outcomes (PROs) in the TARGET trial in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitors (TNF-IR).

Methods: 546 patients (81.9% female, mean age 52.9 years) were randomised to placebo, sarilumab 150 or 200 mg subcutaneously every 2 weeks + csDMARDs. PROs included patient global assessment (PtGA); pain and morning stiffness visual analogue scales; Health Assessment Questionnaire Disability Index (HAQ-DI); Short Form-36 Health Survey (SF-36); FACIT-Fatigue (FACIT-F); Work Productivity Survey-Rheumatoid Arthritis (WPS-RA) and Rheumatoid Arthritis Impact of Disease (RAID). Changes from baseline at weeks 12 and 24 were analysed using a mixed model for repeated measures; post hoc analyses included percentages of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores ≥ normative values.

Results: Sarilumab + csDMARDs doses resulted in improvements from baseline at week 12 vs placebo + csDMARDs in PtGA, pain, HAQ-DI, SF-36 and FACIT-F that were maintained at week 24. Sarilumab improved morning stiffness and reduced the impact of RA on work, family, social/leisure activities participation (WPS-RA) and on patients' lives (RAID). Percentages of patients reporting improvements ≥MCID and ≥ normative scores were greater with sarilumab than placebo.

Conclusions: In patients with TNF-IR RA, 150 and 200 mg sarilumab + csDMARDs resulted in clinically meaningful patient-reported benefits on pain, fatigue, function, participation and health status at 12 and 24 weeks that exceeded placebo + csDMARDs, and were consistent with the clinical profile previously reported.

Trial registration number: NCT01709578; Results.

Keywords: Anti-TNF; DMARDs (biologic); Outcomes research; Patient perspective; Rheumatoid Arthritis.

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Conflict of interest statement

Competing interests: VS has received consulting fees from AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America (CORRONA), Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi and UCB. MR, CWJP, SG, HvH, DB and YL are employees of Sanofi Genzyme and may hold stock and/or stock options in the company. CIC, EM and NMHG are employees of Regeneron Pharmaceuticals, and may hold stock and/or stock options in the company. CP-T has been principal investigator for Roche, Bristol-Myers Squibb, MS, Vertex, Sanofi, AstraZeneca, Johnson & Johnson, Novo Nordisk and AbbVie and has received speaker fees from Roche, Bristol-Myers Squibb, AbbVie, UCB, Janssen and MSD. RF has received research grants from AbbVie, Amgen, Ardea, AstraZeneca, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Pfizer, Roche, Sanofi Aventis and UCB; and has received consulting fees from AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, Roche and UCB.

Figures

Figure 1
Figure 1
Spydergram of mean SF-36 domain scores at baseline and weeks 12 (A) and 24 (B) for sarilumab 150 mg and 200 mg+csDMARDs compared with placebo+csDMARDs relative to age- and gender-matched general population norms. All scores on a scale of 0 to 100 (0=worst, 100=best). For week 12, n=181 for placebo, n=165 for sarilumab 150 mg and n=184 for sarilumab 200 mg; for week 24, n=99 for placebo, n=126 for sarilumab 150 mg and n=135 for sarilumab 200 mg. BP, Bodily Pain; GH, General Health Perceptions; MH, Mental Health; NS, not significant; PF, Physical Functioning; RE, Role Emotional; RP, Role Physical; SF, Social Functioning; VT, Vitality.
Figure 2
Figure 2
Change from baseline at week 24 in Work Productivity Survey-Rheumatoid Arthritis; recall period is the past month. (A) Work outside of the home. (B) Household work. (C) Days missed of family, social, leisure activities. Scale for rate of interference is 0=no interference to 10=complete interference; all other scales represent days. *p<0.05 vs placebo; †p<0.0001 vs placebo; ‡p<0.001 vs placebo. csDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs.
Figure 3
Figure 3
Post hoc analysis of differences from placebo in the percentage of patients reporting improvements ≥MCID at week 24. (A) Patient global assessment (PtGA), Pain visual analogue scale, FACIT-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), SF-36 physical and mental component scores (PCS and MCS), morning stiffness visual analogue scale and Rheumatoid Arthritis Impact of Disease (RAID). (B) SF-36 individual domains. *p<0.05 for the response rate relative to placebo. †p<0.0001 for the response rate relative to placebo. ‡p<0.001 for the response rate relative to placebo. BP, Bodily Pain; csDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs; GH, General Health perceptions; MH, Mental Health; NNT, number needed to treat; PF, Physical Functioning; RE, Role Emotional; RP, Role Physical; SF, Social Functioning; VT, Vitality.
Figure 4
Figure 4
Correlations between observed patient-reported outcomes and disease activity scores at week 24. Positive correlations indicate similar directionality of scales; negative correlations indicate opposing directionality. BP, Bodily Pain; CDAI, Clinical Disease Activity Index; DAS28-CRP, 28-joint Disease Activity using C reactive protein; FACIT-F, Functional Assessment of Chronic Illness Therapy–Fatigue scale; GH, General Health perceptions; HAQ-DI, Health Assessment Questionnaire Disability Index; MH, Mental Health; PF, Physical Functioning; PtGA, patient global assessment of disease activity; RE, Role Emotional; RP, Role Physical; SF-36, Short Form 36 Health Survey V.2. SF, Social Functioning; VT, Vitality.
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