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SAT0117 Sarilumab, a Subcutaneously-Administered, Fully-Human Monoclonal Antibody Inhibitor of The IL-6 Receptor: Relationship Between Eular Responses and Change from Baseline of Selected Clinical Parameters
  1. M. C. Genovese1,
  2. R. M. Fleischmann2,
  3. S. Fiore3,
  4. A. Radin4,
  5. C. Fan3,
  6. T. W. Huizinga5
  1. 1Stanford Univ School of Medicine, Palo Alto
  2. 2Metroplex Clinical Research Center, Dallas
  3. 3Sanofi, Bridgewater
  4. 4Regeneron, Tarrytown, United States
  5. 5Leiden Univ Medical Centre, Leiden, Netherlands

Abstract

Background Modification of signs and symptoms and improvement in quality of life are key goals for clinical management of RA patients (pts). Sarilumab (SAR) is the first fully human monoclonal antibody directed against the alpha subunit of the IL-6 receptor (IL-6Rα). In the phase 2 MOBILITY Part A trial, SAR administered SC in combination with MTX achieved its primary endpoint of ACR20 at week 12 and guided selection of 2 doses (150 and 200 mg q2w) studied in Phase 3.

Objectives This post hoc analyis evaluates the relationship between EULAR responses at week 12 and change from baseline of 2 clinical and 2 laboratory parameters (sleep [VAS], FACIT, Hb and hsCRP).

Methods Patients were randomized to 6 groups: placebo, SAR 100, 150, 200 mg every other week (q2w) and 100, 150 mg weekly (qw). Disease characteristics, including those for anemia (Hb), systemic inflammation (hsCRP), fatigue (FACIT) and sleep (VAS) scores, were collected at baseline and then every 2 weeks.

Results Baseline characteristics were similar across all groups (n=306): mean age 52.2±12.3 yrs; 79% women; mean disease duration 7.8±8.1 yrs; RF+ 79.7%; mean hsCRP 2.8±3.0 mg/dL. The proportion of patients achieving improved PROs, Hb, hsCRP and a EULAR good response was higher in the 2 Phase 3 dose groups vs placebo. Table 1 shows improvement at week 12 in pt reported outcomes (PROs), Hb and hsCRP for pts achieving a EULAR good response; similar findings were seen with SAR vs placebo (data not shown). Only FACIT and sleep VAS improvements were significantly better in the evaluation by EULAR good response vs. other responses (p =0.0010 [FACIT], p=0.0151 [VAS]). The most common TEAEs reported in all SAR arms were infections (non-serious) 12-26%, neutropenia 0-20%, and ALT increase 0-6%. Eight patients (none in the 2 Phase 3 doses, 2 on placebo) experienced at least 1 treatment emergent SAE (1 death due to respiratory distress syndrome/cerebrovascular accident in 100mg q2w); of these 6 led to permanent treatment discontinuation. There were no infection-related SAEs in patients with grade 3 or 4 neutropenia.

Conclusions Sarilumab doses studied in Phase 3 resulted in a significantly higher proportion of RA patients with improved Hb, hsCRP and EULAR good responses compared to placebo. This preliminary evaluation of a subset of PROs in MOBILITY Part A shows improvements in FACIT and sleep VAS scores that correlated with achievement of a EULAR good response.

Acknowledgements MOBILITY Part A trial (NCT01061736) was funded by Sanofi and Regeneron

Disclosure of Interest M. Genovese Grant/research support from: Sanofi, Regeneron, Consultant for: Sanofi, Regeneron, R. Fleischmann Grant/research support from: Sanofi, Regeneron, Consultant for: Sanofi, Regeneron, S. Fiore Shareholder of: Sanofi, Employee of: Sanofi, A. Radin Shareholder of: Regeneron, Employee of: Regeneron, C. Fan Shareholder of: Sanofi, Employee of: Sanofi, T. Huizinga Grant/research support from: Sanofi, Regeneron, Consultant for: Sanofi, Regeneron

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