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Safety of JAK inhibitor use in patients with rheumatoid arthritis who developed herpes zoster after receiving JAK inhibitors

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Abstract

Introduction

To determine the safety of Janus kinase inhibitor (JAKi) use following herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA).

Methods

Medical records of all patients who received JAKi at a tertiary referral center between August 2015 and June 2021 were retrospectively reviewed. Data from patients who developed HZ reactivation were collected, and the HZ-related safety of those who continued JAKis after reactivation was evaluated.

Results

Of the 416 patients who received JAKis, 33 (7.9%) developed HZ reactivation during treatment (tofacitinib, n = 22; baricitinib, n = 11). The mean age of the patients was 60.2 ± 11.8 years. Fourteen patients (42.4%) received glucocorticoids with a median dose of 3.75 mg of prednisone (IQR, 2.5–5.0). The median duration of JAKi administration before HZ reactivation was 11 months (IQR, 4–29). JAKi was continued in 24 (72.7%) patients during the HZ episode, while it was temporarily discontinued and then resumed after the HZ episode in 5 (15.2%) patients. Three (9.1%) patients had acute complications, such as encephalitis with HZ ophthalmicus. Four (12.1%) patients, including the 3 with complications, permanently discontinued JAKis. Of the 29 patients who were observed for a median of 12 months (IQR, 6–21) after the initial HZ reactivation episode, reactivation recurred in one (3.4%); this patient maintained JAKi treatment for a further 18 months without additional HZ recurrence.

Conclusion

JAKis were commonly continued or re-administered in patients with HZ reactivation, and the majority of these patients did not experience significant complications or recurrence of HZ reactivation. Thus, the use of JAKi after HZ reactivation episode seems to be tolerated.

Key Points

JAK inhibitor was generally continued or re-administered after HZ reactivation

Most patients receiving JAK inhibitor after the HZ episode did not experience recurrence of HZ

Resuming JAK inhibitor following HZ seems to be safe

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References

  1. Cohen JI (2013) Clinical practice: herpes zoster. N Engl J Med 369:255–263

    Article  CAS  Google Scholar 

  2. Le P, Rothberg M (2019) Herpes zoster infection. BMJ 364:k5095

    Article  Google Scholar 

  3. Thomas SL, Hall AJ (2004) What does epidemiology tell us about risk factors for herpes zoster? Lancet Infect Dis 4:26–33

    Article  Google Scholar 

  4. Smitten AL, Choi HK, Hochberg MC, Suissa S, Simon TA, Testa MA et al (2007) The risk of herpes zoster in patients with rheumatoid arthritis in the United States and the United Kingdom. Arthritis Rheum 57:1431–1438

    Article  Google Scholar 

  5. Chakravarty EF, Michaud K, Katz R, Wolfe F (2013) Increased incidence of herpes zoster among patients with systemic lupus erythematosus. Lupus 22:238–244

    Article  CAS  Google Scholar 

  6. Gupta G, Lautenbach E, Lewis JD (2006) Incidence and risk factors for herpes zoster among patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 4:1483–1490

    Article  Google Scholar 

  7. Veetil BM, Myasoedova E, Matteson EL, Gabriel SE, Green AB, Crowson CS (2013) Incidence and time trends of herpes zoster in rheumatoid arthritis: a population-based cohort study. Arthritis Care Res (Hoboken) 65:854–861

    Article  Google Scholar 

  8. McDonald JR, Zeringue AL, Caplan L, Ranganathan P, Xian H, Burroughs TE et al (2009) Herpes zoster risk factors in a national cohort of veterans with rheumatoid arthritis. Clin Infect Dis 48:1364–1371

    Article  Google Scholar 

  9. Harigai M (2019) Growing evidence of the safety of JAK inhibitors in patients with rheumatoid arthritis. Rheumatology (Oxford) 58:i34–i42

    Article  CAS  Google Scholar 

  10. Winthrop KL, Yamanaka H, Valdez H, Mortensen E, Chew R, Krishnaswami S et al (2014) Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis. Arthritis Rheumatol 66:2675–2684

    Article  CAS  Google Scholar 

  11. Winthrop KL, Harigai M, Genovese MC, Lindsey S, Takeuchi T, Fleischmann R et al (2020) Infections in baricitinib clinical trials for patients with active rheumatoid arthritis. Ann Rheum Dis 79:1290–1297

    Article  CAS  Google Scholar 

  12. Smolen JS, Pangan AL, Emery P, Rigby W, Tanaka Y, Vargas JI et al (2019) Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet 393:2303–2311

    Article  Google Scholar 

  13. Curtis JR, Xie F, Yun H, Bernatsky S, Winthrop KL (2016) Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis 75:1843–1847

    Article  CAS  Google Scholar 

  14. Cohen SB, van Vollenhoven RF, Winthrop KL, Zerbini CAF, Tanaka Y, Bessette L et al (2020) Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis 80:304-311

  15. Winthrop KL, Curtis JR, Lindsey S, Tanaka Y, Yamaoka K, Valdez H et al (2017) Herpes zoster and tofacitinib: clinical outcomes and the risk of concomitant therapy. Arthritis Rheumatol 69:1960–1968

    Article  CAS  Google Scholar 

  16. Harigai M, Takeuchi T, Smolen JS, Winthrop KL, Nishikawa A, Rooney TP et al (2020) Safety profile of baricitinib in Japanese patients with active rheumatoid arthritis with over 1.6 years median time in treatment: an integrated analysis of phases 2 and 3 trials. Mod Rheumatol 30:36–43

    Article  CAS  Google Scholar 

  17. Sunzini F, McInnes I, Siebert S (2020) JAK inhibitors and infections risk: focus on herpes zoster. Ther Adv Musculoskelet Dis 12:1759720X20936059

    Article  CAS  Google Scholar 

  18. Curtis JR, Xie F, Yang S, Bernatsky S, Chen L, Yun H et al (2019) Risk for herpes zoster in tofacitinib-treated rheumatoid arthritis patients with and without concomitant methotrexate and glucocorticoids. Arthritis Care Res (Hoboken) 71:1249–1254

    Article  CAS  Google Scholar 

  19. Winthrop KL, Nash P, Yamaoka K, Mysler E, Khan N, Camp HS et al (2022) Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials. Ann Rheum Dis 81:206–213

    Article  CAS  Google Scholar 

  20. Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL et al (2021) Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther 9:243-263

  21. Kawai K, Gebremeskel BG, Acosta CJ (2014) Systematic review of incidence and complications of herpes zoster: towards a global perspective. BMJ Open 4:e004833

    Article  Google Scholar 

  22. Arnold N, Messaoudi I (2017) Herpes zoster and the search for an effective vaccine. Clin Exp Immunol 187:82–92

    Article  CAS  Google Scholar 

  23. Ansaldi F, Trucchi C, Alicino C, Paganino C, Orsi A, Icardi G (2016) Real-world effectiveness and safety of a live-attenuated herpes zoster vaccine: a comprehensive review. Adv Ther 33:1094–1104

    Article  CAS  Google Scholar 

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Funding

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and funded by the Korean government (MSIT) (No. 2018M3A9D3079500).

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Correspondence to Seokchan Hong.

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Choi, W., Ahn, S.M., Kim, YG. et al. Safety of JAK inhibitor use in patients with rheumatoid arthritis who developed herpes zoster after receiving JAK inhibitors. Clin Rheumatol 41, 1659–1663 (2022). https://doi.org/10.1007/s10067-022-06096-0

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  • DOI: https://doi.org/10.1007/s10067-022-06096-0

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