PMID- 37349636 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231116 IS - 2198-6576 (Print) IS - 2198-6584 (Electronic) IS - 2198-6576 (Linking) VI - 10 IP - 4 DP - 2023 Aug TI - Real-World Sarilumab Use and Rule Testing to Predict Treatment Response in Patients with Rheumatoid Arthritis: Findings from the RISE Registry. PG - 1055-1072 LID - 10.1007/s40744-023-00568-8 [doi] AB - INTRODUCTION: Clinical trial findings may not be generalizable to routine practice. This study evaluated sarilumab effectiveness in patients with rheumatoid arthritis (RA) and tested the real-world applicability of a response prediction rule, derived from trial data using machine learning (based on C-reactive protein [CRP] > 12.3 mg/l and seropositivity [anticyclic citrullinated peptide antibodies, ACPA +]). METHODS: Sarilumab initiators from the ACR-RISE Registry, with >/= 1 prescription on/after its FDA approval (2017-2020), were divided into three cohorts based on progressively restrictive criteria: Cohort A (had active disease), Cohort B (met eligibility criteria of a phase 3 trial in RA patients with inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi]), and Cohort C (characteristics matched to the phase 3 trial baseline). Mean changes in Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) were evaluated at 6 and 12 months. In a separate cohort, predictive rule was tested based on CRP levels and seropositive status (ACPA and/or rheumatoid factor); patients were categorized into rule-positive (seropositive with CRP > 12.3 mg/l) and rule-negative groups to compare the odds of achieving CDAI low disease activity (LDA)/remission and minimal clinically important difference (MCID) over 24 weeks. RESULTS: Among sarilumab initiators (N = 2949), treatment effectiveness was noted across cohorts, with greater improvement noted for Cohort C at 6 and 12 months. Among the predictive rule cohort (N = 205), rule-positive (vs. rule-negative) patients were more likely to reach LDA (odds ratio: 1.5 [0.7, 3.2]) and MCID (1.1 [0.5, 2.4]). Sensitivity analyses (CRP > 5 mg/l) showed better response to sarilumab in rule-positive patients. CONCLUSIONS: In real-world setting, sarilumab demonstrated treatment effectiveness, with greater improvements in the most selective population, mirroring phase 3 TNFi-refractory and rule-positive RA patients. Seropositivity appeared a stronger driver for treatment response than CRP, although optimization of the rule in routine practice requires further data. CI - (c) 2023. The Author(s). FAU - Curtis, Jeffrey R AU - Curtis JR AUID- ORCID: 0000-0002-8907-8976 AD - University of Alabama at Birmingham, Birmingham, AL, 35233, USA. jrcurtis@uabmc.edu. FAU - Yun, Huifeng AU - Yun H AD - University of Alabama at Birmingham, Birmingham, AL, 35233, USA. FAU - Chen, Lang AU - Chen L AD - University of Alabama at Birmingham, Birmingham, AL, 35233, USA. FAU - Ford, Stephanie S AU - Ford SS AD - University of Alabama at Birmingham, Birmingham, AL, 35233, USA. FAU - van Hoogstraten, Hubert AU - van Hoogstraten H AD - Sanofi, Bridgewater, NJ, USA. FAU - Fiore, Stefano AU - Fiore S AUID- ORCID: 0000-0002-3785-2448 AD - Sanofi, Bridgewater, NJ, USA. FAU - Ford, Kerri AU - Ford K AD - Sanofi, Cambridge, MA, USA. FAU - Praestgaard, Amy AU - Praestgaard A AD - Sanofi, Cambridge, MA, USA. FAU - Rehberg, Markus AU - Rehberg M AD - Sanofi, Frankfurt, Germany. FAU - Choy, Ernest AU - Choy E AUID- ORCID: 0000-0003-4459-8609 AD - CREATE Centre, Cardiff University, Cardiff, UK. LA - eng GR - P30 AR072583/AR/NIAMS NIH HHS/United States PT - Journal Article DEP - 20230622 PL - England TA - Rheumatol Ther JT - Rheumatology and therapy JID - 101674543 EIN - Rheumatol Ther. 2024 Feb;11(1):217. PMID: 37955805 PMC - PMC10326227 OAB - Rheumatoid arthritis (RA) is a condition that may cause joint damage, if untreated. Sarilumab is an advanced medication, approved for treating moderate-to-severe RA in patients not responding to initial standard medicines. Clinical trials have shown that sarilumab improves RA symptoms; however, some people do not respond. This is a common problem in RA treatment. Physicians measure proteins in people's blood (called biomarkers; e.g., anticyclic citrullinated peptide antibodies [ACPA], C-reactive protein [CRP], and rheumatoid factor [RF]) to predict a medicine's response. A previous study showed that people with positive blood tests for ACPA and CRP (> 12.3 mg/l) responded well to sarilumab; this study was based on machine learning (a branch of science using computers) and identified factors that could be linked to treatment benefits. The present study analyzed routine data of 2949 people from the ACR-RISE Registry and showed an improvement in RA symptoms after 6 and 12 months of sarilumab, with a greater improvement noted in patients previously treated with other medicines. Biomarkers were tested in 205 people to check whether they could predict treatment response in day-to-day life. People were called rule-positive if they tested positive for RF and/or ACPA with CRP > 12.3 mg/l, and otherwise rule-negative. After 24 weeks of treatment, rule-positive people had a greater chance of disease improvement than rule-negative people. These results showed the benefits of sarilumab in RA in routine care and suggested the usefulness of machine learning in identifying biomarkers that physicians can use to make treatment decisions. OABL- eng OTO - NOTNLM OT - ACPA OT - CDAI OT - CRP OT - RISE registry OT - Real-world OT - Rheumatoid arthritis OT - Sarilumab OT - Seronegative OT - Seropositive OT - Treatment response COIS- Jeffrey R Curtis received grants/contract from AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Novartis, Pfizer, Sanofi, and UCB; and consulting fees from AbbVie, Amgen, BMS, Corrona, Eli Lilly, Janssen, Myriad, Novartis, Pfizer, Roche, Sanofi, Scipher, and UCB. Huifeng Yun received grant from Pfizer, and recently joined GSK, but all work was completed at UAB. Lang Chen and Stephanie S Ford have nothing to disclose. Hubert van Hoogstraten, Stefano Fiore, Kerri Ford, Amy Praestgaard, and Markus Rehberg are employees of Sanofi and may hold stock/stock options in the company. Ernest Choy received grants or contracts from AbbVie, Amgen, AstraZeneca, Biogen, Bio-Cancer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chelsea Therapeutics, Chugai Pharma, Daiichi Sankyo, Eli Lilly, Ferring Pharmaceuticals, Gilead, GlaxoSmithKline, Hospira Pharmaceuticals, Ionis Pharmaceuticals, Janssen, Jazz Pharmaceuticals, MedImmune, Merck Sharp & Dohme, Merrimack Pharmaceuticals, Napp, Novartis, Novimmune, ObsEva, Pfizer, R-Pharm, Regeneron Pharmaceuticals, Inc., Roche, Sanofi Genzyme, SynAct Pharma, Tonix, and UCB; received consulting fees from AbbVie, Amgen, AstraZeneca, Biogen, Bio-Cancer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chelsea Therapeutics, Chugai Pharma, Daiichi Sankyo, Eli Lilly, Ferring Pharmaceuticals, Gilead, GlaxoSmithKline, Hospira Pharmaceuticals, Ionis Pharmaceuticals, Janssen, Jazz Pharmaceuticals, MedImmune, Merck Sharp & Dohme, Merrimack Pharmaceuticals, Napp, Novartis, Novimmune, ObsEva, Pfizer, R-Pharm, Regeneron Pharmaceuticals, Inc., Roche, Sanofi Genzyme, SynAct Pharma, Tonix, and UCB; received honoraria from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharma, Eli Lilly, Hospira, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Sanofi-Aventis, and UCB. EDAT- 2023/06/23 01:10 MHDA- 2023/06/23 01:11 PMCR- 2023/06/22 CRDT- 2023/06/22 23:32 PHST- 2023/01/18 00:00 [received] PHST- 2023/05/30 00:00 [accepted] PHST- 2023/06/23 01:11 [medline] PHST- 2023/06/23 01:10 [pubmed] PHST- 2023/06/22 23:32 [entrez] PHST- 2023/06/22 00:00 [pmc-release] AID - 10.1007/s40744-023-00568-8 [pii] AID - 568 [pii] AID - 10.1007/s40744-023-00568-8 [doi] PST - ppublish SO - Rheumatol Ther. 2023 Aug;10(4):1055-1072. doi: 10.1007/s40744-023-00568-8. Epub 2023 Jun 22.