Long-term effectiveness of live herpes zoster vaccine in patients with rheumatoid arthritis subsequently treated with tofacitinib

Winthrop, Kevin; Wouters, Ann; Choy, Ernest; Chen, Connie; Biswas, Pinaki; Wang, Lisy; Soma, Koshika; Needle, Elie; Valdez, Hernán; Rigby, William F.C.

doi:10.1136/annrheumdis-2019-216566

Cited by 15 publications

(8 citation statements)

References 6 publications

(12 reference statements)

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“… 32 As a corollary, this observation implies that vaccination against HZ remains important over a patient’s entire course of UPA treatment, and that it is ‘never too late’ to vaccinate. However, it should be noted that a recent study suggested that live attenuated HZ vaccination had limited efficacy in preventing HZ in patients with RA receiving tofacitinib, 33 despite patients showing VZV-specific humoral and cell-mediated immune responses. 34 Further research is required to determine the value of HZ vaccination in patients with RA receiving JAK inhibitors, particularly with the recently approved subunit vaccine (Shingrix).…”

Section: Discussionmentioning

confidence: 99%

Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials

et al. 2021

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BackgroundUpadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA). JAK inhibitors have been associated with an increased risk of herpes zoster (HZ) in patients with RA.ObjectivesTo evaluate the incidence and risk factors for HZ in UPA-treated patients with RA from the UPA phase III clinical trial programme.MethodsExposure-adjusted incidence/event rates for HZ were determined in patients receiving UPA (monotherapy or combination therapy) in six randomised phase III trials (data cut-off on 30 June 2020). HZ incidence and event rates were also determined in patients receiving methotrexate (MTX) monotherapy or adalimumab (ADA) + MTX. Multivariable Cox regression analysis was used to identify HZ risk factors in UPA-treated patients.ResultsA total of 5306 patients were included in this analysis. The incidence rate of HZ/100 patient-years (95% CI) was 0.8 (0.3 to 1.9), 1.1 (0.5 to 1.9), 3.0 (2.6 to 3.5) and 5.3 (4.5 to 6.2), in the MTX monotherapy, ADA + MTX, UPA 15 mg and UPA 30 mg groups, respectively. The majority of HZ cases with UPA (71%) involved a single dermatome. Prior history of HZ and Asian region were HZ risk factors in UPA-treated patients.ConclusionIn the UPA phase III RA clinical programme, HZ incidence and event rates were higher with UPA versus ADA + MTX or MTX monotherapy, and higher with the 30 mg versus 15 mg dose. Patients from Asia and those with a history of HZ may be at increased risk of HZ while receiving UPA.

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Section: Discussionmentioning

confidence: 99%

Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials

et al. 2021

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“… 42 However, of 100 patients with RA who entered a tofacitinib OLE study 14 weeks post-vaccination, 5 patients experienced HZ infection, 3 of whom had undetectable VZV cell-mediated immunity at baseline and week 6. 43 Use of live vaccines concurrently with tofacitinib is not recommended however, 44 and LZV was recently discontinued in the US. 45…”

Section: Discussionmentioning

confidence: 99%

Long-term Risk of Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib

Winthrop

Vermeire

Long

et al. 2022

Inflammatory Bowel Diseases

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Background Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We report herpes zoster (HZ) incidence and risk factors in the tofacitinib UC clinical program (up to 7.8 years). Methods Proportions and incidence rates (IRs; unique patients with events/100 patient-years) of HZ were evaluated in 4 cohorts: Induction (phase 2 and 3 induction study data), Maintenance (phase 3 maintenance study data), Overall (data from all phase 2, 3, and open-label, long-term extension studies), and Overall plus interim 6-month phase 3b and 4 data. Herpes zoster risk factors were assessed by Cox regression analysis. Results In the Induction and Maintenance Cohorts, IRs for HZ (nonserious and serious) were numerically higher with tofacitinib 10 mg twice daily (BID) vs placebo and tofacitinib 10 vs 5 mg BID, respectively. With all tofacitinib doses (5 or 10 mg BID), IRs (95% confidence intervals) for HZ in the Overall and Overall plus phase 3b/4 Cohorts (total exposure, 2814.4 and 2999.7 patient-years, respectively) were 3.38 (2.73-4.15) and 3.30 (2.67-4.04), respectively. In the Overall plus phase 3b/4 Cohort, >90% of HZ were nonserious; >90% were mild/moderate; >90% resolved without discontinuing tofacitinib; 0.6% of patients had multiple HZ events. Herpes zoster IRs were stable when analyzed by 6-month intervals up to >30 months. Herpes zoster risk factors included older age, lower weight, geographic region, and prior tumor necrosis factor inhibitor (TNFi) failure. Conclusions Most HZ events were mild/moderate. Herpes zoster IRs remained stable over 7.8 years of exposure. Older age, lower weight, geographic region, and prior TNFi failure were associated with increased HZ risk. ClinicalTrials.gov NCT00787202;NCT01465763;NCT01458951;NCT01458574;NCT01470612;NCT03281304

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“…In the VAHS cohort, vaccination in IBD patients was associated with a significant reduction of HZ risk versus unvaccinated patients (adjusted hazard ratio of 0.54) 75 . In contrast, Winthrop et al 76 reported that LZR may not provide adequate long-term protection in a long-term effectiveness study of RA patients treated with tofacitinib.…”

Section: Efficacy Datamentioning

confidence: 93%

Herpes Zoster and Vaccination Strategies in Inflammatory Bowel Diseases: A Practical Guide

Guillo

Choy

D’Amico

et al. 2022

Clinical Gastroenterology and Hepatology

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Long-term effectiveness of live herpes zoster vaccine in patients with rheumatoid arthritis subsequently treated with tofacitinib

Cited by 15 publications

References 6 publications

Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials

Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials

Long-term Risk of Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib

Herpes Zoster and Vaccination Strategies in Inflammatory Bowel Diseases: A Practical Guide

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