Drug retention of sarilumab, baricitinib, and tofacitinib in patients with rheumatoid arthritis: the ANSWER cohort study

Ebina, Kosuke; Hirano, Tôru; Maeda, Yukihide; Yamamoto, Wataru; Hashimoto, Motomu; Murata, Koichi; Ōnishi, Akira; Jinno, Sadao; Hara, Ryota; Son, Yonsu; Amuro, Hideki; Takeuchi, Tohru; Yoshikawa, Ayaka; Katayama, Masaki; Yamamoto, Keiichi; Hirao, Makoto; Okita, Yasutaka; Kumanogoh, Atsushi; Nakata, Ken

doi:10.1007/s10067-021-05609-7

Cited by 19 publications

(15 citation statements)

References 30 publications

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“…In this analysis, primary nonresponse was the main reason for discontinuation, irrespective of treatment with baricitinib or any other tsDMARD or any bDMARD. This finding is consistent with reports from the USA [ 9 ], Japan [ 30 , 31 ], and previous database searches [ 12 ], where the loss of efficacy or lack of effectiveness were the key reasons for discontinuations among patients receiving bDMARDs and/or tsDMARDs. Of note, in the current study, the proportion with primary nonresponse was 3.3% for baricitinib-treated patients and 5.8% for patients treated with another tsDMARD or any bDMARD.…”

Section: Discussionsupporting

confidence: 92%

The RA-BE-REAL Multinational, Prospective, Observational Study in Patients with Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, or Biologic Disease-Modifying Therapies: a 6-Month Interim Analysis

et al. 2022

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Introduction RA-BE-REAL has the overall aim of defining a profile of patients with rheumatoid arthritis (RA) starting baricitinib or any other targeted synthetic (ts) or any biologic (b) disease-modifying antirheumatic drug (DMARD) for the first time, and the primary objective of estimating time until discontinuation from any cause (excluding sustained response) of the initial treatment. Methods RA-BE-REAL is an ongoing, prospective, observational, 36-month study in patients with RA initiating treatment with baricitinib (cohort A) or any other tsDMARD or any bDMARD (cohort B) for the first time. The primary objective is to assess the time until treatment discontinuation from any cause (excluding sustained response) at 24 months, (i.e., the rate of discontinuation of initial baricitinib or ts/bDMARD). Patient profiles of each cohort are described and compared. Post-baseline data are descriptively analyzed. This manuscript presents baseline and interim (6-month) outcomes for European patients with RA participating in the global RA-BE-REAL study. Results Data from 1074 patients (cohort A: 509; cohort B: 565) were analyzed. For cohorts A and B, respectively, the 6-month cumulative incidence (95% confidence interval) of treatment discontinuation was 16.5 (12.9–21.1) and 23.3 (19.1–28.2), and the proportions of patients achieving remission were 25.6% and 18.5%. At baseline, mean patient age was 59.1 and 57.0 years ( p = 0.010) and mean disease duration was 10.0 and 8.9 years ( p = 0.047), respectively. The proportions of patients exposed to ts/bDMARDs at any time before study entry were 51.9% and 39.1%, and the proportions of patients initiated on monotherapy were 50.9% and 31.2%, respectively. Conclusion In real-world settings, patients with RA initiating treatment with baricitinib were older and had longer disease duration than those initiating treatment with any other tsDMARD or any bDMARD. Initial descriptive data regarding treatment discontinuation (including reasons for discontinuation), effectiveness, and treatment patterns will be enriched as the study progresses. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-022-00500-6.

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Section: Discussionsupporting

confidence: 92%

The RA-BE-REAL Multinational, Prospective, Observational Study in Patients with Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, or Biologic Disease-Modifying Therapies: a 6-Month Interim Analysis

et al. 2022

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“…From a total of 2961 references (after de-duplication), 226 were selected for a full-text review and 59 observational studies fulfilled the inclusion criteria 16–74. In addition, 2 RCTs with a primary safety outcome,2 3 and 28 RCTs/LTEs from the efficacy SLR,75–102 were included (flow chart in online supplemental figure S1).…”

Section: Resultsmentioning

confidence: 99%

“…Of 59 observational studies, 51 assessed only 1 outcome,16–66 and 8 addressed ≥2 outcomes (online supplemental table S1–137). 67–74 Of 27 studies evaluating the risk of infections,27–47 67 69 71–74 23 included patients on bDMARDs,27–29 31–33 35–37 39–47 69 71–74 9 of which also patients on JAKi,27 28 30 31 42 45 69 71 72 3 only patients on csDMARDs34 38 67 and 1 patients either on tofacitinib or on csDMARDs 30.…”

Section: Resultsmentioning

confidence: 99%

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

et al. 2022

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ObjectivesTo perform a systematic literature review (SLR) concerning the safety of synthetic(s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) to inform the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis (RA).MethodsSLR of observational studies comparing safety outcomes of any DMARD with another intervention in RA. A comparator group was required for inclusion. For treatments yet without, or limited, registry data, randomised controlled trials (RCTs) were used.ResultsFifty-nine observational studies addressed the safety of DMARDs. Two studies (unclear risk of bias (RoB)) showed an increased risk of serious infections with bDMARDs compared with conventional synthetic (cs)DMARDs. Herpes zoster infections occurred more with JAKi than csDMARDs (adjusted HR (aHR): 3.66) and bDMARDs (aHR: 1.9–2.3) (four studies, two low RoB). The risk of malignancies was similar across bDMARDs (five studies) and with tofacitinib compared with bDMARDs (one study, low RoB). The risk of major adverse cardiovascular events (MACE) was similar with bDMARDs and tofacitinib (two studies, one low RoB). Thirty studies reported safety from RCTs, with one, designed to evaluate safety, showing that malignancies (HR (95% CI): 1.48 (1.04 to 2.09)) and MACE (HR (95% CI): 1.33 (0.91 to 1.94)) occurred numerically more frequently with tofacitinib (5 mg and 10 mg doses combined) than with TNFi in patients with cardiovascular risk factors. In this study, the risk of venous thromboembolism (VTE) was higher with tofacitinib 10 mg than with TNFi.ConclusionThe safety profile of bDMARDs was further demonstrated. Whether the difference in incidence of malignancies, MACE and VTE between tofacitinib and TNFi applies to other JAKi needs further evaluation.

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“…The Kansai Consortium for Well-being of Rheumatic Disease Patients (ANSWER) cohort is an observational, multicenter registry of patients with RA in the Kansai district of Japan [7][8][9][10][11][12]. Data were retrospectively collected from patients who were examined at seven major university-related hospitals (Kyoto University, Osaka University, Osaka Medical College, Kansai Medical University, Kobe University, Nara Medial University and Osaka Red Cross Hospital).…”

Section: Patientsmentioning

confidence: 99%

“…The performance of bDMARDs has increasingly been investigated through recent cohort-based observational studies [3,4] in which drug retention is considered a major index of both treatment safety and effectiveness [5,6]. We have recently reported the drug retention rates of bDMARDs [7][8][9][10][11][12], factors affecting the e cacy of bDMARDs [13,14] and factors affecting the achievement of bDMARDs-free remission [15] on the basis of ndings from our cohort. The aim of the present multicenter, retrospective study is to clarify the factors affecting drug retention of a JAKi (BAR or TOF) in real-world settings.…”

Section: Introductionmentioning

confidence: 99%

Factors Affecting Drug Retention of Janus kinase Inhibitors in Patients with Rheumatoid Arthritis: The ANSWER Cohort Study

Ebina

Hirano

Maeda

et al. 2021

Preprint

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Background: This multi-center, retrospective study aimed to clarify the factors affecting drug retention of the Janus kinase inhibitors (JAKi) baricitinib (BAR) and tofacitinib (TOF) in patients with RA.Methods: Patients were included as follows: females, 80.6%; age, 60.5 years; DAS28-ESR, 4.3; treated with either BAR (n = 166) or TOF (n = 185) and concomitant glucocorticoid (prednisolone [PSL] equivalent) 5.3 mg/day (46.7%) or methotrexate (MTX) 8.9 mg/week (60.7%); bDMARDs- or JAKi-switched cases (76.6%). The reasons for drug discontinuation were classified into four major categories: lack of effectiveness, toxic adverse events, non-toxic reasons and remission. The drug retention rate was estimated at 24 months using the Kaplan–Meier method and adjusted for potential confounders using multivariate Cox proportional hazards modelling.Results: Adjusted discontinuation rates for the corresponding reasons were as follows: lack of effectiveness (22.3%), toxic adverse events (13.3%), non-toxic reasons (7.2%) and remission (0.0%). Prior use of anti-interleukin-6 receptor antibody (aIL-6R) was significantly associated with discontinuation due to lack of effectiveness (P = 0.021). Ageing (P = 0.015), usage of PSL ≥5 mg/day (P = 0.017) and female sex (P = 0.041) were significantly associated with discontinuation due to toxic adverse events. Factors not associated with treatment discontinuation were: number of prior bDMARDs or JAKi, concomitant MTX usage, different JAKi and prior use of TNF inhibitor, CTLA4-Ig or other JAKi.Conclusions: Prior use of aIL-6R was associated with discontinuation due to lack of effectiveness, while ageing (≥75 years), PSL usage ≥5 mg/day, and female sex were associated with discontinuation due to toxic adverse events.

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Drug retention of sarilumab, baricitinib, and tofacitinib in patients with rheumatoid arthritis: the ANSWER cohort study

Cited by 19 publications

References 30 publications

The RA-BE-REAL Multinational, Prospective, Observational Study in Patients with Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, or Biologic Disease-Modifying Therapies: a 6-Month Interim Analysis

The RA-BE-REAL Multinational, Prospective, Observational Study in Patients with Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, or Biologic Disease-Modifying Therapies: a 6-Month Interim Analysis

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

Factors Affecting Drug Retention of Janus kinase Inhibitors in Patients with Rheumatoid Arthritis: The ANSWER Cohort Study

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