PMID- 33199274 OWN - NLM STAT- MEDLINE DCOM- 20221230 LR - 20221230 IS - 1468-2060 (Electronic) IS - 0003-4967 (Print) IS - 0003-4967 (Linking) VI - 80 IP - 4 DP - 2021 Apr TI - Efficacy and safety of fasinumab in patients with chronic low back pain: a phase II/III randomised clinical trial. PG - 509-517 LID - 10.1136/annrheumdis-2020-217259 [doi] AB - OBJECTIVES: To study the efficacy and safety of fasinumab in moderate-to-severe, chronic low back pain (CLBP). METHODS: In this phase II/III, double-blind, placebo-controlled study, patients with CLBP aged >/=35 years with inadequate pain relief/intolerance to acetaminophen, non-steroidal anti-inflammatory drugs and opioids were randomised to fasinumab 6 or 9 mg subcutaneous every 4 weeks (Q4W), 9 mg intravenous every 8 weeks (Q8W) or placebo. Primary endpoint was change from baseline to week 16 in average daily low back pain intensity (LBPI) numeric rating score. Key secondary efficacy variables included Roland-Morris Disability Questionnaire (RMDQ) and Patient Global Assessment (PGA). The results are based on a modified intent-to-treat analysis of 563/800 planned patients when enrolment was stopped early given emerging signals of joint risk in other osteoarthritis (OA) studies at doses being tested here. RESULTS: Significant placebo-adjusted LBPI reductions at week 16 were observed for fasinumab 9 mg Q4W and Q8W (least squares mean (standard error) -0.7 (0.3); both nominal p<0.05), but not 6 mg (-0.3 (0.3); p=0.39). RMDQ and PGA improvements to week 16 were greatest for fasinumab 9 mg intravenous. Numerically greater efficacy occurred in patients with, versus those without, peripheral OA (pOA) over 16 weeks. Treatment-emergent adverse events (AEs) occurred in 274/418 (65.6%) patients in the combined fasinumab groups and 94/140 (67.1%) placebo patients. Joint AEs, mostly rapid progressive OA type 1, were more frequent in the combined fasinumab groups (19 events in 16 patients (3.8%) vs 1 event in 1 patient (0.7%) for placebo); all except one occurred in pOA patients. CONCLUSIONS: Fasinumab highest doses, but not lower dose, improved both CLBP pain and function. Most joint AEs occurred in pOA patients, consistent with earlier findings in symptomatic OA. Further study is needed of patients with CLBP with and without pOA to determine optimal benefit-risk. CI - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Dakin, Paula AU - Dakin P AUID- ORCID: 0000-0002-8925-0414 AD - Global Clinical Development, Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA. FAU - Kivitz, Alan J AU - Kivitz AJ AD - Department of Rheumatology, Altoona Center for Research, Duncansville, Pennsylvania, USA. FAU - Gimbel, Joseph S AU - Gimbel JS AUID- ORCID: 0000-0002-6254-2417 AD - Arizona Research Center, Phoenix, Arizona, USA. FAU - Skrepnik, Nebojsa AU - Skrepnik N AUID- ORCID: 0000-0002-2589-574X AD - Research Center, Tucson Orthopedic Institute, Tucson, Arizona, USA. FAU - DiMartino, Stephen J AU - DiMartino SJ AD - Global Clinical Development, Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA. FAU - Emeremni, Chetachi A AU - Emeremni CA AD - R&D, Regeneron Pharmaceuticals Inc, Basking Ridge, New Jersey, USA. FAU - Gao, Haitao AU - Gao H AD - R&D, Regeneron Pharmaceuticals Inc, Basking Ridge, New Jersey, USA. FAU - Stahl, Neil AU - Stahl N AD - Global Clinical Development, Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA. FAU - Weinreich, David M AU - Weinreich DM AUID- ORCID: 0000-0003-0971-1530 AD - Global Clinical Development, Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA. FAU - Yancopoulos, George D AU - Yancopoulos GD AD - Global Clinical Development, Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA. FAU - Geba, Gregory P AU - Geba GP AUID- ORCID: 0000-0001-8936-748X AD - Global Clinical Development, Regeneron Pharmaceuticals Inc, Tarrytown, New York, USA gregory.geba@regeneron.com. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20201116 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 11T51Q3082 (fasinumab) SB - IM MH - Humans MH - Antibodies, Monoclonal, Humanized/adverse effects MH - *Chronic Pain/drug therapy MH - Double-Blind Method MH - *Low Back Pain/drug therapy MH - *Osteoarthritis/drug therapy MH - Pain Measurement MH - Treatment Outcome PMC - PMC7958114 OTO - NOTNLM OT - analgesics OT - fibromyalgis/pain syndromes OT - low back pain OT - osteoarthritis COIS- Competing interests: PD, SJD, CAE, HG, GPG, NS, DMW and GDY are employees of Regeneron Pharmaceuticals. JG reports consulting fees from Pfizer and participation in other activities with Regeneron Pharmaceuticals outside the submitted work. AJK reports participation in other activities with Altoona Center for Clinical Research, PC, during the conduct of the study; and other activities from AbbVie, Celgene, Horizon, Janssen, Merck, Novartis, Pfizer, UCB, Genzyme, Sanofi, Regeneron Pharmaceuticals, SUN Pharma Advanced Research, Boehringer Ingelheim, Flexion, Amgen and Gilead, outside the submitted work. NS reports grants from Regeneron Pharmaceuticals during the conduct of this study; and personal fees from Regeneron Pharmaceuticals and Orthofix, outside the submitted work. EDAT- 2020/11/18 06:00 MHDA- 2022/06/28 06:00 PMCR- 2021/03/15 CRDT- 2020/11/17 06:11 PHST- 2020/03/04 00:00 [received] PHST- 2020/10/21 00:00 [revised] PHST- 2020/10/22 00:00 [accepted] PHST- 2020/11/18 06:00 [pubmed] PHST- 2022/06/28 06:00 [medline] PHST- 2020/11/17 06:11 [entrez] PHST- 2021/03/15 00:00 [pmc-release] AID - annrheumdis-2020-217259 [pii] AID - 10.1136/annrheumdis-2020-217259 [doi] PST - ppublish SO - Ann Rheum Dis. 2021 Apr;80(4):509-517. doi: 10.1136/annrheumdis-2020-217259. Epub 2020 Nov 16.