Background: In randomized studies (RCTs: MOBILITY, TARGET and MONARCH), and open-label [OLE] EXTEND, for those patients who experienced decreases in ANC this typically occurred early after initiating sarilumab. For sarilumab patients with decreased ANC in the RCTs and the OLE, we assessed the outcomes associated with either continuing treatment, decreasing the sarilumab dose or delaying the dose.

Objectives: The effects of a dose decrease (200 to 150 mg), dose delay (>17 days), vs no change in treatment were evaluated in RA patients who experienced decreased ANC while on sarilumab 150 or 200 mg q2w. Outcomes data from patients in MONARCH, MOBILITY and TARGET, and MOBILITY and TARGET patients entering EXTEND were analyzed to compare the three strategies. In MONARCH, patients received sarilumab 200 mg q2w. In MOBILITY and TARGET, patients received sarilumab 150 or 200 mg q2w. In EXTEND, patients were switched to, or initiated on, 200 mg q2w.

Methods: In RCTs, patients were required to have baseline neutrophil levels ≥2000/mm³. In RCTs and EXTEND, patients who experienced ANC <500/mm³ (grade 4 [G4] neutropenia) or ≥500 to <1000/mm³ (grade 3 [G3] neutropenia) and signs of infection were required to permanently discontinue treatment. Patients with G3 neutropenia (no signs of infection) temporarily discontinued treatment (or permanently discontinued at the investigators discretion); patients were retested ≤48 hrs after identifying decreased ANC and before the next scheduled dose, and could resume if ANC ≥1000/mm³. In RCTs, patients restarted sarilumab at their randomized dose. In OLE, patients restarted sarilumab at 150 mg q2w, as per the protocol, or otherwise were able to restart at 200 mg q2w at the investigators discretion. In OLE, patients who required a dose decrease to 150 mg q2w sarilumab received the reduced dose for the remainder of the treatment period. ANC normalization was defined as a return to the patient’s baseline or within normal ranges.

Results: Of the 8–11% of patients who experienced ANC <1000/mm³ at any time, 81/105 (RCTs) and 132/147 (OLE) were able to continue or reinitiate sarilumab; the majority of patients who experienced ANC <1000/mm³ one or more times displayed normalized ANC levels and continued treatment when ANC ≥1000/mm³ (25/38 in RCTs; 29/31 in OLE). The majority of patients who dose delayed (27/43 in RCTs; 66/82 in OLE) or dose decreased (51/62, OLE) before ANC normalized resumed treatment.

Conclusions: More than three-quarters of patients who discontinued treatment until ANC normalized were able to reinitiate at their randomized dose (RCT), or at the open-label study dose (200 mg q2w; OLE) or were able to resume at the lower dose (150 mg q2w; OLE).

Acknowledgements: Study funding and medical writing support (Julie Gray, Adelphi) provided by Sanofi and Regeneron Pharmaceuticals, Inc.

Disclosure of Interest: J. R. Curtis Grant/research support from: Abbvie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Consultant for: Abbvie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, G. St John Shareholder of: Regeneron, Employee of: Regeneron, M. Panucci Shareholder of: Regeneron, Employee of: Boehringer Ingellheim, Regeneron, J. A. Maldonado-Cocco Consultant for: Pfizer, Merck Sharp & Dohme, Sanofi-Aventis, Novartis, Bristol-Myers Squibb, Roche, Boehringer Ingelheim, Schering-Plough, Abbott, UCB, Eli Lilly, Gilead, Speakers bureau: Pfizer, Merck Sharp & Dohme, Sanofi-Aventis, Novartis, Bristol-Myers Squibb, Roche, Boehringer Ingelheim, Schering-Plough, Abbott, UCB, Eli Lilly, Gilead