Preferable outcome of Janus kinase inhibitors for a group of difficult-to-treat rheumatoid arthritis patients: from the FIRST Registry

Sae Ochi; Koshiro Sonomoto; Shingo Nakayamada; Yoshiya Tanaka

doi:10.1186/s13075-022-02744-7

Preferable outcome of Janus kinase inhibitors for a group of difficult-to-treat rheumatoid arthritis patients: from the FIRST Registry

Arthritis Res Ther. 2022 Mar 1;24(1):61. doi: 10.1186/s13075-022-02744-7.

Authors

Sae Ochi^{1

2}, Koshiro Sonomoto², Shingo Nakayamada², Yoshiya Tanaka³

Affiliations

¹ Department of Laboratory Medicine, The Jikei University School of Medicine, Nishi-shinbashi 3-25-8, Minatoku, Tokyo, 105-8461, Japan.
² The First Department of Internal Medicine, School of Medicine University of Occupational and Environmental Health, Japan, Iseigaoka1-1, Yahata-Nishiku, Kitakyushu, 807-8555, Japan.
³ The First Department of Internal Medicine, School of Medicine University of Occupational and Environmental Health, Japan, Iseigaoka1-1, Yahata-Nishiku, Kitakyushu, 807-8555, Japan. tanaka@med.uoeh-u.ac.jp.

Abstract

Backgrounds: Treatment of difficult-to-treat rheumatoid arthritis (D2T RA) is one of the greatest unmet needs in rheumatology. This study aims to find out preferable treatment options for a group of D2T RA patients who are refractory to multiple biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs).

Methods: Data were obtained from patients enrolled in the FIRST Registry who started either TNF inhibitor (TNFi), interleukin-6 receptor inhibitor, cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin, or Janus-kinase inhibitor (JAKi) in the period of August 2013 to December 2020. Those who failed to ≥ 2 and ≥ 3 b/tsDMARDs were categorised as D2T RA and very D2T RA (vD2T RA), respectively. Change in Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire Disability Index were compared among the groups using propensity-based inverse probability treatment weighted (IPTW) method.

Results: Of 2128 cases included, 353 were categorised as D2T RA. Among the D2T RA, 106 were identified as vD2T RA. JAKi showed a significant improvement in CDAI in the patients with D2T RA and vD2T RA, compared to IPTW-adjusted patients treated with the other 3 regimens. Latent class analysis of the trajectories of treatment response revealed that the proportion of a group of patients who showed poor response was lower among the JAKi subgroup than among those with other subgroups. This superiority of JAKi was more apparent among methotrexate- and glucocorticoid-free individuals. The hazard ratio of severe adverse events was comparable among the four treatment subgroups in both the D2T RA and b/tsDMARD-naïve groups.

Conclusions: This study compared responsiveness to different classes of b/tsDMARDs among D2T RA and vD2T RA patients who were refractory to multiple b/tsDMARDs. The results suggest JAKi is a preferable treatment choice for this type of D2T RA.

Keywords: Biologic and targeted synthetic disease-modifying anti-rheumatic drugs; Difficult-to-treat rheumatoid arthritis; Janus kinase inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antirheumatic Agents* / therapeutic use
Arthritis, Rheumatoid* / drug therapy
Humans
Janus Kinase Inhibitors* / therapeutic use
Registries
Rheumatology*

Substances

Antirheumatic Agents
Janus Kinase Inhibitors