Risk of disease flare in spondyloarthritis patients after tapering tumor necrosis factor inhibitors: A meta-analysis and literature review

Hong Ki Min; Hae-Rim Kim; Sang-Heon Lee; Bora Nam; Ji Hui Shin; Tae-Hwan Kim

doi:10.1016/j.intimp.2024.112167

Risk of disease flare in spondyloarthritis patients after tapering tumor necrosis factor inhibitors: A meta-analysis and literature review

Int Immunopharmacol. 2024 May 15:134:112167. doi: 10.1016/j.intimp.2024.112167. Online ahead of print.

Authors

Hong Ki Min¹, Hae-Rim Kim², Sang-Heon Lee², Bora Nam³, Ji Hui Shin⁴, Tae-Hwan Kim⁵

Affiliations

¹ Division of Rheumatology, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea; Division of Rheumatology, Department of Internal Medicine, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
² Division of Rheumatology, Department of Internal Medicine, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea.
³ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea; Hanyang University Institute for Rheumatology Research (HYIRR), Seoul, Republic of Korea.
⁴ Hanyang University Institute for Rheumatology Research (HYIRR), Seoul, Republic of Korea.
⁵ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea; Hanyang University Institute for Rheumatology Research (HYIRR), Seoul, Republic of Korea. Electronic address: thkim@hanyang.ac.kr.

PMID: 38754279
DOI: 10.1016/j.intimp.2024.112167

Abstract

Background: Tumor necrosis factor inhibitors (TNFis) have shown dramatic benefit in patients with spondyloarthritis (SpA). Tapering of TNFi medication may be considered in patients with sustained low disease activity because continued use of TNFis at standard doses may increase the risk of side effects including infections and impose an economic burden. However, the optimal TNFi tapering strategy for SpA patients with inactive disease has not been established. In the present study, we investigated whether tapering TNFi doses is associated with similar risk of disease flare to maintaining SpA patients on TNFis at the standard dosage.

Methods: The MEDLINE, Embase, and Cochrane databases were systemically searched to retrieve randomized control trials (RCTs) and observational studies published prior to August 2023, that compared disease flare in SpA (including axial SpA [axSpA], psoriatic arthritis [PsA], and SpA with IBD) patients who received standard TNFi doses and those who received a tapered dose of TNFi. Odds ratios (ORs) and 95% confidence intervals (CIs) were directly retrieved or calculated, and meta-analyses were performed. Bias was assessed using funnel plots with Begg and Mazumdar rank correlation / Egger's regression method.

Results: Among 2,237 SpA patients in the 12 studies (9 RCTs and 3 observational studies) retrieved, 1,301 received the standard TNFi dose, while 936 SpA patients underwent TNFi tapering. Of these, 216 (16.6%) standard-dose TNFi and 217 (23.2%) TNF-tapering patients experienced disease flares. The pooled OR for disease flare in TNFi-tapering patients was 1.601 (95% CI 1.276 - 2.008) compared with the standard-dose patients. The funnel plot showed no publication bias.

Conclusions: The strategy of TNFi tapering was associated with a significantly increased risk of disease flare compared to maintaining SpA patients at the standard TNF dose. Further studies are needed to determine which patients can safely undergo tapering of TNFi and to develop safe tapering strategies.

Keywords: Adverse event; Disease activity; Predictor; Spondyloarthritis; Tapering; Tumor necrosis factor inhibitor.