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Comparative Study
. 2022 Jan;81(1):41-47.
doi: 10.1136/annrheumdis-2021-220651. Epub 2021 Jul 28.

Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register

Imke Redeker  1 , Katinka Albrecht  1 , Joern Kekow  2 , Gerd Rüdiger Burmester  3 , Juergen Braun  4 , Martin Schäfer  1 , Angela Zink  1 , Anja Strangfeld  5
Affiliations
Comparative Study

Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register

Imke Redeker et al. Ann Rheum Dis. 2022 Jan.

Abstract

Objective: To compare event and incidence rates of herpes zoster (HZ), also known as shingles, in patients with rheumatoid arthritis under treatment with conventional synthetic (cs), targeted synthetic (ts) or biologic (b) disease-modifying antirheumatic drugs (DMARDs).

Methods: Patients were prospectively enrolled from 2007 until October 2020. Reported HZ events were assigned to ongoing treatments or those terminated within 1 month prior to the HZ event. Exposure-adjusted event rates (EAERs) of HZ were calculated per 1000 patient years (py) and adjusted HRs with 95% CIs computed. Inverse probability weights (IPW) were used to adjust for confounding by indication.

Results: Data of 13 991 patients (62 958 py) were analysed, with 559 HZ events reported in 533 patients. The EAER of HZ was highest for tsDMARDs (21.5, 95% CI 16.4 to 27.9), followed by B cell targeted therapy (10.3, 95% CI 8.0 to 13.0), monoclonal antitumour necrosis factor (anti-TNF) antibodies (9.3, 95% CI 7.7 to 11.2), interleukin 6 inhibitors (8.8, 95% CI 6.9 to 11.0), soluble TNF receptor fusion protein (8.6, 95% CI 6.8 to 10.8), T cell costimulation modulator (8.4, 95% CI 5.9 to 11.8) and csDMARDs (7.1, 95% CI 6.0 to 8.3). Adjusted for age, sex and glucocorticoids and weighted with IPW, tsDMARDs (HR 3.66, 95% CI 2.38 to 5.63), monoclonal anti-TNF antibodies (HR 1.63, 95% CI 1.17 to 2.28) and B cell targeted therapy (HR 1.57, 95% CI 1.03 to 2.40) showed a significantly higher risk compared with csDMARDs.

Conclusion: Our results provide evidence for a 3.6-fold increased risk of HZ associated with tsDMARDs and an increased risk of HZ under bDMARDs compared with csDMARDs.

Keywords: DMARDs; arthritis; biological therapy; rheumatoid; tumour necrosis factor inhibitors.

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Conflict of interest statement

Competing interests: AS has received speaking fees from Bristol-Myers Squibb, Celltrion, MSD, Pfizer and Roche. AZ has received speaking fees from AbbVie, Janssen, Pfizer, Roche and Sanofi-Aventis. G-RRB has received honoraria for lectures and consulting from AbbVie, BMS, Galapagos, Lilly, MSD, Pfizer, Roche and Sanofi. JB has received honoraria for talks, advisory boards, paid consultancies and grants for studies from AbbVie (Abbott), Amgen, Baxter, Biogen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Fresenius, GlaxoSmithKline, Gilead, Hexal, Janssen, Lilly, Medac, MSD (Schering-Plough), Mylan, Mundipharma, Novartis, Pfizer (Wyeth, Hospira), Roche, Sanofi-Aventis and UCB.

Figures

Figure 1
Figure 1
Exposure-adjusted event rates of all herpes zoster per 1000 patient years. csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; IL-6, interleukin 6; JAK, Janus kinase; TNF, tumour necrosis factor.
Figure 2
Figure 2
Exposure-adjusted event rates of serious herpes zoster per 1000 patient years. csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; IL-6, interleukin 6; JAK, Janus kinase; TNF, tumour necrosis factor.
See this image and copyright information in PMC

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