PMID- 31090044 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 2198-6576 (Print) IS - 2198-6584 (Electronic) IS - 2198-6576 (Linking) VI - 6 IP - 3 DP - 2019 Sep TI - Immunogenicity of Sarilumab Monotherapy in Patients with Rheumatoid Arthritis Who Were Inadequate Responders or Intolerant to Disease-Modifying Antirheumatic Drugs. PG - 339-352 LID - 10.1007/s40744-019-0157-3 [doi] AB - INTRODUCTION: This open-label study evaluated the immunogenicity, safety, and efficacy of sarilumab monotherapy in patients with active, moderate-to-severe rheumatoid arthritis (RA) and inadequate response or intolerance to prior conventional synthetic disease-modifying antirheumatic drugs. METHODS: Adults with RA (n = 132) were randomized to receive subcutaneous sarilumab (150 [n = 65] or 200 mg [n = 67]) every 2 weeks (q2w) for 24 weeks. Endpoints included incidence of antidrug antibodies (ADAs) at week 24, safety, and efficacy. RESULTS: Persistent ADAs occurred in eight patients (12.3%) receiving sarilumab 150 mg q2w, seven of whom (10.8%) had neutralizing antibodies (NAbs), and in four patients (6.1%) receiving sarilumab 200 mg q2w, two of whom (3.0%) had NAbs; all exhibited low antibody titers. Infections and neutropenia were the most common adverse events (AEs). There were three serious AEs, no reports of anaphylaxis, and few hypersensitivity reactions (e.g., rash) with no notable differences in hypersensitivity reactions in ADA-positive patients relative to ADA-negative patients. Changes in absolute neutrophil count, alanine aminotransferase level, and platelet count were consistent with interleukin-6 signaling blockade and in agreement with previous observations. At week 24, overall American College of Rheumatology 20%/50%/70% improvement criteria responses were 73.8%/53.8%/29.2%, respectively, with sarilumab 150 mg q2w and 71.6%/50.7%/29.9% with sarilumab 200 mg q2w. No patients with an ADA-positive response showed loss of efficacy. CONCLUSIONS: ADA titers were low and persistent ADAs and NAbs occurred relatively infrequently in both sarilumab dose groups. ADA did not meaningfully impact the safety or efficacy of either dose of sarilumab over 24 weeks. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02121210. FUNDING: Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Plain language summary available for this article. FAU - Wells, Alvin F AU - Wells AF AD - Rheumatology and Immunology Center, Franklin, WI, USA. a.f.wells@att.net. FAU - Parrino, Janie AU - Parrino J AD - Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. FAU - Mangan, Erin K AU - Mangan EK AD - Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. FAU - Paccaly, Anne AU - Paccaly A AD - Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. FAU - Lin, Yong AU - Lin Y AD - Sanofi Genzyme, Bridgewater, NJ, USA. FAU - Xu, Christine AU - Xu C AD - Sanofi Genzyme, Bridgewater, NJ, USA. FAU - Fan, Chunpeng AU - Fan C AD - Sanofi Genzyme, Bridgewater, NJ, USA. FAU - Graham, Neil M H AU - Graham NMH AD - Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. FAU - van Hoogstraten, Hubert AU - van Hoogstraten H AD - Sanofi Genzyme, Bridgewater, NJ, USA. FAU - Torri, Albert AU - Torri A AD - Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. LA - eng SI - ClinicalTrials.gov/NCT02121210 PT - Journal Article DEP - 20190514 PL - England TA - Rheumatol Ther JT - Rheumatology and therapy JID - 101674543 PMC - PMC6702535 OTO - NOTNLM OT - Arthritis OT - Biological DMARDs OT - Rheumatoid arthritis EDAT- 2019/05/16 06:00 MHDA- 2019/05/16 06:01 PMCR- 2019/05/14 CRDT- 2019/05/16 06:00 PHST- 2019/02/27 00:00 [received] PHST- 2019/05/16 06:00 [pubmed] PHST- 2019/05/16 06:01 [medline] PHST- 2019/05/16 06:00 [entrez] PHST- 2019/05/14 00:00 [pmc-release] AID - 10.1007/s40744-019-0157-3 [pii] AID - 157 [pii] AID - 10.1007/s40744-019-0157-3 [doi] PST - ppublish SO - Rheumatol Ther. 2019 Sep;6(3):339-352. doi: 10.1007/s40744-019-0157-3. Epub 2019 May 14.