S. Fiore, L. Chen, C. Clinton, H. Yun, A. Praestgaard, K. Ford, J. Curtis
2021 Annals of the Rheumatic Diseases  
Background:Patients with rheumatoid arthritis (RA) who have received multiple biologics or targeted therapies over time tend to have more refractory and more severe disease, which may lead to worse clinical response to treatment.Objectives:We used data from the ACR RISE registry to assess whether disease severity was greater in those who received sarilumab shortly after its FDA approval (May 2017) than in subsequent time periods and to evaluate the effectiveness of sarilumab in populations with
more » ... various degrees of disease severity.Methods:Patients with RA who initiated sarilumab treatment in the period 2017-2020 were identified in the ACR RISE registry and divided into Cohort 1 (2017, year of the FDA approval) and the calendar year-based Cohorts 2-4 (2018-2020). Patient demographics, RA-related features, and comorbidities were determined using data prior to sarilumab initiation. The cohorts were compared using chi-square test (categorical variables) and a nonparametric test (continuous variables). Sarilumab effectiveness was assessed using 3 cohorts assembled based on progressively restrictive criteria: Active Disease cohort (Clinical Disease Activity Index [CDAI] >10 or Routine Assessment of Patient Index Data 3 [RAPID3] >6, and C-reactive protein, if measured, ≥8 mg/L), TARGET Eligibility cohort (patients who satisfied enrolment criteria for TARGET,1 a Phase 3 sarilumab trial in patients with RA and an inadequate response to TNF inhibitors), and TARGET Baseline cohort (patients from TARGET Eligibility cohort with characteristics weighted to match those from the TARGET trial baseline,1 using the matching-adjusted indirect comparison method2). In all 3 effectiveness cohorts, mean changes in CDAI and RAPID3 at 6 and 12 months post-initiation of sarilumab were evaluated using a model adjusted for baseline score, age, sex, race, calendar year, and seropositivity.Results:A total of 2949 patients, treated by 585 rheumatologists, initiated sarilumab treatment in the period 2017–2020. The 4 yearly cohorts were relatively similar in terms of patients' age, sex, race, and most clinical characteristics. However, patients receiving sarilumab shortly after FDA approval (Cohort 1) had more ambulatory visits, a greater number of previously used non-TNFi biologics (particularly tocilizumab), and a higher comorbidity burden, and were more likely to be current users of glucocorticoids or opioids than sarilumab initiators in the subsequent 3 years. In the 3 cohorts used to assess sarilumab effectiveness, the greatest improvement was observed in the TARGET Baseline cohort, which also had the greatest mean baseline CDAI score (43), compared with the other two (24 both).Conclusion:In this real-world cohort, we observed modest evidence for channeling of patients with greater RA severity and greater prior exposure to non-TNFi biologics to sarilumab shortly after its FDA approval. This cohort effect did not diminish the effectiveness of sarilumab. All cohorts showed improvement, with the greatest clinical improvement observed in the cohort with the highest baseline CDAI score who most closely resembled those enrolled in a phase 3 trial of patients with an inadequate response to TNF inhibitors.References:[1]Fleischmann R, et al. Arthritis Rheumatol 2017;69:277-290.[2]Signorovitch JE et al. Value Health 2012;15:940-7.Figure 1.Adjusted improvements in CDAI and RAPID3Acknowledgements:This study was sponsored by Sanofi. Medical writing support was provided by Vojislav Pejović, PhD (Eloquent Medical Affairs, division of Envision Pharma Group) and funded by Sanofi.Disclosure of Interests:Stefano Fiore Employee of: Sanofi, Lang Chen: None declared, Cassie Clinton Consultant of: Information available in profile, Huifeng Yun Grant/research support from: Research support for Pfizer, Amy Praestgaard Employee of: Sanofi, Kerri Ford Employee of: Sanofi, Jeffrey Curtis Consultant of: Received consulting and research grants from AbbVie, Amgen, BMS, Lilly, Gilead, GSK, Janssen, Myriad, Pfizer, Roche, Samsung, Sandoz, Sanofi, UCB, Grant/research support from: Received consulting and research grants from AbbVie, Amgen, BMS, Lilly, Gilead, GSK, Janssen, Myriad, Pfizer, Roche, Samsung, Sandoz, Sanofi, UCB
doi:10.1136/annrheumdis-2021-eular.3655 fatcat:33zvqlfh2vehzfsw46njuwiitm