Comparison of Drug Tolerability and Discontinuation Reasons between 7 Biologics in Patients with Rheumatoid Arthritis -Results from Kansai Consortium for Well-Being of Rheumatic Disease Patients (ANSWER cohort)- ACR Meeting Abstracts

Kosuke Ebina¹, Makoto Hirao², Motomu Hashimoto³, Moritoshi Furu⁴, Wataru Yamamoto⁵, Ryota Hara⁶, Takanori Fujimura⁶, Toru Hirano⁷, Shuzo Yoshida⁸, Koji Nagai⁸, Hideki Amuro⁹, Yonsu Son⁹, Akira Onishi¹⁰, Kengo Akashi¹¹, Masaki Katayama¹², Keiichi Yamamoto¹³ and Hideki Yoshikawa¹⁴, ¹Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan, ²Orthopaedic Surgery, Osaka University, Graduate School of Medicine, Suita, Japan, ³Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan, ⁴Graduate School of Medicine, Kyoto University, Kyoto, Japan, ⁵Kurashiki Sweet Hospital, Okayama, Japan, ⁶The Center for Rheumatic Diseases, Nara Medical University, Kashihara, Japan, ⁷Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Suita, Japan, ⁸Osaka Medical College, Osaka, Japan, ⁹Kansai Medical University, Osaka, Japan, ¹⁰Kobe University Graduate School of Medicine, Kobe, Japan, ¹¹Department of Rheumatology and Clinical Immnology, Kobe University Graduate School of Medicine, Kobe, Japan, ¹²Osaka Red Cross Hospital, Osaka, Japan, ¹³Osaka City University, Osaka, Japan, ¹⁴Department of Orthopedics, Osaka University Graduate School of Medicine, Suita Osaka, Japan

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Biologic agents and rheumatoid arthritis, treatment

Session Information

Date: Sunday, November 5, 2017

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy Poster I: Comorbidities and Adverse Events; Efficacy and Safety of Small Molecules

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: 　More than 4 years have passed since 7 biologics became available for patients with rheumatoid arthritis (RA) in Japan, still lack reliable evidence in their differences of tolerability and discontinuation reasons.

Methods: 　A total of 1,037 biologics treatment courses of RA from 2009 to 2016 [female 81.8%, baseline age 59.6 y, disease duration 7.8y, bio continued duration 17.1 months, RF positivity 81.5%, ACPA positivity 86.7%, DAS28-ESR 4.4, CDAI 16.8, HAQ 1.1, Bio naïve 57.1% and switched 42.9%, methotrexate (MTX) 5.9 mg/week (limited to 16mg/week in Japan) (68.6%), prednisolone (PSL) 2.5 mg/day (43.5%), abatacept (ABT) 21.3%, tocilizumab (TCZ) 20.7%, golimumab (GLM) 16.9%, etanercept (ETN) 13.6%, adalimumab (ADA) 11.1%, infliximab (IFX) 8.5%, certolizumab pegol (CZP) 7.9%] were included in this 7-center, retrospective study. The drug tolerability and discontinuation reasons at 36 months were estimated using Kaplan-Meier method, and adjusted by potent confounders [Sex / Age / Bio started date / Disease duration / ACPA positivity / RF positivity / bio naive or switched / combined csDMARDs (MTX, tacrolimus, bucillamine, salazosulfapyridine, iguratimod) and PSL / baseline DAS28-ESR / HAQ] which may affect biologics retention rates using a Cox proportional hazards model.

Results: 　There were no significant differences in the baseline disease activity (DAS28-ESR and CDAI). The major causes of 7 biologics treatment discontinuation were as follows. Drug inefficacy (47.7%), other nontoxic reasons (12.3%), remission (8.6%), infection (7.5%), patients’ preference (7.5%), other adverse events such as malignant, cardiovascular, pulmonary, renal, hematologic complications (6.2%), skin or systemic reaction (5.3%), and changing hospital (5.1%). Adjusted discontinuation reasons and ratio at 36 months in each drug were as follows. Drug inefficacy (TCZ 16.1%, ABT 23.7%, ETN 28.4%, CZP 32.9%, IFX 33.3%, ADA 42.3%, and GLM 46.1%; P=0.14), remission (IFX 11.4%, ADA 2.6%, ETN 1.4%, ABT 0.5%, TCZ 0.5%, GLM 0.0%, and CZP 0.0%; P<0.001), infection (ABT 1.4%, TCZ 1.5%, GLM 2.0%, ETN 2.3%, ADA 2.5%, IFX 4.0%, and CZP 5.5%; P=0.77), other adverse events (ABT 1.2%, ETN 2.0%, CZP 4.9%, GLM 5.6%, ADA 7.2%, TCZ 8.5%, and IFX 11.7%; P=0.03), and skin or systemic reaction (ABT 0.0%, TCZ 0.5%, GLM 1.1%, ADA 1.7%, ETN 2.1%, CZP 3.7%, and IFX 4.5%; P=0.02), respectively. Adjusted total retention rates at 36 months were as follows. TCZ 58.9%, ABT 55.1%, CZP 51.4%, ETN 50.2%, GLM 37.6%, ADA 32.7%, and IFX 21.7% (P=0.006).

Conclusion: 　When adjusted by potent confounders, TCZ showed lowest inefficacy and highest retention rate, ABT showed lowest infection, skin or systemic reaction, or other toxic adverse events rate, and IFX showed highest remission discontinuation rate at 36 months compared to other biologics in RA.

Disclosure: K. Ebina, Chugai Pharmaceutical, Eisai, Ono Pharmaceutical, Mitsubishi Tanabe Pharma, UCB Japan, 8; M. Hirao, None; M. Hashimoto, Astellas Pharma, 2,Tanabe-Mitsubishi, Chugai, Ayumi, UCB, Bristol-Meyers, 5; M. Furu, None; W. Yamamoto, None; R. Hara, None; T. Fujimura, None; T. Hirano, Mitsubishi Tanabe Pharma Corporation Chugai Pharmaceutical Co., Ltd. AbbVie, Ono Pharmaceutical, Astellas Pharma Inc., 5; S. Yoshida, None; K. Nagai, None; H. Amuro, None; Y. Son, None; A. Onishi, None; K. Akashi, None; M. Katayama, None; K. Yamamoto, None; H. Yoshikawa, Chugai Pharmaceutical, Eisai, Ono Pharmaceutical, Mitsubishi Tanabe Pharma, Phizer, Astellas Pharma, 2.

To cite this abstract in AMA style:

Ebina K, Hirao M, Hashimoto M, Furu M, Yamamoto W, Hara R, Fujimura T, Hirano T, Yoshida S, Nagai K, Amuro H, Son Y, Onishi A, Akashi K, Katayama M, Yamamoto K, Yoshikawa H. Comparison of Drug Tolerability and Discontinuation Reasons between 7 Biologics in Patients with Rheumatoid Arthritis -Results from Kansai Consortium for Well-Being of Rheumatic Disease Patients (ANSWER cohort)- [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/comparison-of-drug-tolerability-and-discontinuation-reasons-between-7-biologics-in-patients-with-rheumatoid-arthritis-results-from-kansai-consortium-for-well-being-of-rheumatic-disease-patients-answ/. Accessed .

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparison-of-drug-tolerability-and-discontinuation-reasons-between-7-biologics-in-patients-with-rheumatoid-arthritis-results-from-kansai-consortium-for-well-being-of-rheumatic-disease-patients-answ/