Association between low hemoglobin, clinical measures, and patient-reported outcomes in patients with rheumatoid arthritis: results from post hoc analyses of three phase III trials of sarilumab

Abstract

Background: Anemia is common in patients with rheumatoid arthritis (RA). Higher hemoglobin (Hb) levels may be associated with better clinical outcomes and patient-reported outcomes (PROs). To assess this hypothesis, we conducted two post hoc analyses in three sarilumab phase III studies: TARGET, MOBILITY, and MONARCH.

Methods: Pooled data from combination therapy from placebo-controlled MOBILITY (sarilumab + methotrexate) and TARGET (sarilumab + conventional synthetic disease-modifying antirheumatic drugs [csDMARDs]) and monotherapy data from active-controlled MONARCH (sarilumab vs. adalimumab) studies were included. Associations between Hb levels and clinical measures and PROs were assessed over 24 weeks. The mean changes from baseline in clinical outcomes and PROs (to week 24) and radiographic outcomes (to week 52) were evaluated between low and normal Hb levels (based on the World Health Organization [WHO] criteria).

Results: From TARGET, MOBILITY, and MONARCH, 546, 1197, and 369 patients, respectively, were stratified according to Hb levels (low vs. normal). Over 24 weeks, higher Hb levels were found to be consistently associated with better clinical outcomes and PROs in combination therapy and monotherapy groups and were more pronounced among the patients treated with sarilumab than those treated with placebo and adalimumab. The mean change from baseline to week 24 in clinical efficacy measures and PROs was similar in patients with low vs. normal Hb at baseline. Differences between sarilumab and/or adalimumab, for all outcomes, were larger for low Hb subgroups. In MOBILITY, by week 52, the inhibition of progression of structural damage (assessed via Modified Total Sharp Score [mTSS]) was 84% (sarilumab 200 mg) and 68% (sarilumab 150 mg) vs. placebo in patients with low Hb and 97% (sarilumab 200 mg) and 68% (sarilumab 150 mg) vs. placebo in patients with normal Hb. Similar results were observed for other radiographic outcomes.

Conclusions: In these post hoc analyses, a consistent relationship was observed between higher Hb levels and better clinical outcomes and PROs in patients with RA. Irrespective of the baseline Hb levels, sarilumab treatment was associated with improvements in clinical measures and PROs over 24 weeks (improvements were more pronounced than those with adalimumab treatment) and mitigation of joint damage progression over 52 weeks.

Trial registration: ClinTrials.gov NCT01061736, NCT01709578, and NCT02332590.

Keywords: Anemia; Hemoglobin; MOBILITY; MONARCH; Patient-reported outcomes; Radiographic outcomes; Rheumatoid arthritis; Sarilumab; TARGET.

Conflict of interest statement

A. RR. has received honoraria for lectures and consultation from Sanofi, Abbvie, Lilly, Gilead, Roche, BMS, Boehringer, Novartis, Janssen, UCB, and Amgen.

D. F. has received grants and/or consulting fees from Actelion, Amgen, Bristol-Myers Squibb, Corbus, Galapagos, GlaxoSmithKline, Horizon, Kadmon, NIH, Novartis, Pfizer, Roche/Genentech, Talaris, and Sanofi Genzyme/Regeneron.

S. F. and A. P. are employees of Sanofi and may hold stock and/or stock options in the company.

V. B. has received consulting fees from Amgen; Bristol-Myers Squibb; Gilead; Pfizer; Regeneron Pharmaceuticals, Inc.; Sanofi Genzyme; and UCB, and her host institution has received research grants from Amgen, the Cedar Hill Foundation, and National Institutes of Health.

C. B. has received grants and/or consulting fees from AbbVie, Bristol-Myers Squibb, Janssen, Lilly, Pfizer, and Sanofi Genzyme/Regeneron.

C. CS. has received grants and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Gilead, Octopharma, Pfizer, and Sanofi Genzyme/Regeneron.

G.B. has received grant/research support, consulting fees, and/or speaker fees/honoraria from AbbVie, Lilly, Merck Sharp & Dohme, Pfizer, Roche, Sanofi Genzyme, and UCB.

© 2022. The Author(s).

Figures

Fig. 1

Relationship between Hb levels and clinical efficacy outcomes: CDAI and DAS-28 CRP over time. Slicefit plots of CDAI and DAS-28 CRP (Y-axis) against hemoglobin (g/L) (X-axis) by a visit from baseline to week 24. Patients with non-missing CRP (mg/L) and hemoglobin (g/L) values were considered. Each panel in the regression model shows the relationship between an outcome and Hb level at a given point in time, stratified by treatment. The lines, with shading, depict the treatment-specific regression coefficient (i.e., slope) and 95% CI associated with the linear regression in which Hb is the independent variable and the outcome is the dependent variable. CDAI, Clinical Disease Activity Index; CRP, C-reactive protein; DAS, Disease Activity Scores; Hb, hemoglobin; q2w, every 2 weeks

Fig. 2

Relationship between Hb levels and clinical efficacy outcomes: PtGA and pain VAS over time. Slicefit plots of PtGA (MM) and pain VAS (MM) (Y-axis) against hemoglobin (g/L) (X-axis) by a visit from baseline to week 24. Each panel in the regression model shows the relationship between an outcome and Hb level at a given point in time, stratified by treatment. The lines, with shading, depict the treatment-specific regression coefficient (i.e., slope) and 95% CI associated with the linear regression in which Hb is the independent variable and the outcome is the dependent variable. Hb, hemoglobin; pain VAS, pain visual analog scale; PtGA, Patient Global Assessment; q2w, every 2 weeks

Fig. 3

Mean change in treatment outcomes over time (stratified by Hb level at baseline)—MONARCH. CDAI, Clinical Disease Activity Index; CRP, C-reactive protein; DAS28-CRP, Disease Activity Score-28 for Rheumatoid Arthritis with CRP; Hb, hemoglobin; PtGA, Patient Global Assessment; MDGA, Physician Global Assessment; q2w, every 2 weeks; VAS, visual analog scale

Fig. 4

Mean change in mTSS from baseline at week 24 and week 52 (95% CI)—MOBILITY. All patients received weekly MTX, and sarilumab or placebo were administered q2w. At week 52, low Hb: P < 0.001 by rank ANCOVA for each sarilumab dose vs. placebo; normal Hb: rank ANCOVA P < 0.001 for 200 mg and P < 0.01 for 150 mg sarilumab dose vs. placebo. Hb, hemoglobin; mTSS, Modified Total Sharp Score; MTX, methotrexate; q2w, every 2 weeks; SD, standard deviation