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Herpes zoster was commonly reported with baricitinib in placebo-controlled studies for up to 16 weeks (≥ 1/100 to < 1/10). Reporting rates for baricitinib compared to placebo for herpes zoster were 1,4 % vs. 0,4 %.1
Incidence of Herpes Zoster in Baricitinib Clinical Trials
The HZ cluster of preferred terms was used to identify cases of HZ in the BARI safety database.
Incidence rates were calculated as the number of patients with an event per 100 patient-years of exposure time, with exposure censored at time of event.2
Herpes zoster IRs for safety integrated analysis sets through 13 February 2018 are presented in Figure 1. Herpes Zoster Incidence Rate by Analysis Dataset through 13 February 2018 .
Figure 1. Herpes Zoster Incidence Rate by Analysis Dataset through 13 February 20182
Abbreviations: BARI = baricitinib; IR = incidence rate; PYE = patient-years exposure; RA = rheumatoid arthritis.
*p<.05 for BARI 4 mg vs placebo
a Maximum severity: mild, 41.5%; moderate, 53.3%; severe, 5.2%.
The 7-study pooled dataset included patients with RA randomized to BARI 4 mg (N=1142, PYE=471.8) or placebo (N=1215, PYE=450.8) from 3 phase 2 studies and 4 phase 3 studies (RA-BEAM, RA-BUILD, RA-BEACON and RA-BALANCE). Patients in the placebo group could have been taking background MTX or other conventional DMARDs. Evaluation time periods included through
the 12-week placebo-controlled period in phase 2 studies
16 weeks of assigned treatment before any opportunity for rescue therapy in phase 3 studies, and
Data from BARI 2 mg (N=479, PYE=185.8) is derived from 4 of these studies in which both BARI 2 mg and BARI 4 mg were options during randomization (2 phase 2 studies as well as RA-BUILD and RA-BEACON).2,3
Through 24 weeks of assigned treatment or until rescue, the HZ IR for BARI 4-mg group (3.8) was statistically significantly higher than the placebo group (0.9; p<.05) and numerically higher than BARI 2-mg group (3.1).3
The extended dataset included patients with RA randomized to BARI 4 mg (N=479, PYE=698.6) or BARI 2 mg (N=479, PYE=675.6) from 2 phase 2 and 2 phase 3 studies (RA-BUILD, RA-BEACON) and 1 long term extension study (RA-BEYOND). The evaluation time periods included randomization through last available observation incorporating extension data through 13 February 2018 unless otherwise specified. Data were censored at rescue or dose change.2,3
In the 4-study extended dataset through 13 February 2018, the IR of HZ infections was numerically but not statistically significantly higher in the BARI 4-mg group (IR=3.9) than the BARI 2-mg group (IR=2.7).3 For more information see Figure 1. Herpes Zoster Incidence Rate by Analysis Dataset through 13 February 2018 .
The All BARI RA analysis set included 3770 patients with RA who received BARI at a variety of doses from 1 phase 1, 3 phase 2, and 5 phase 3 studies (RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, RA-BALANCE). Data includes a long-term extension study (RA-BEYOND) with
Herpes Zoster Events and Case Details
Of the 3770 patients who received BARI in clinical trials for the treatment of RA through 13 February 2018,
323 had a treatment-emergent case of HZ, and
the overall IR was 3.3/100 PYs of observation.3
Of the 323 HZ cases reported through 13 February 2018,
95% of cases were mild to moderate in severity
8% of cases were multidermatomal, and
0 had visceral involvement.4
Risk Factor Analyses
Based on multivariate analyses, a higher risk of HZ was associated with
older age ( ≥50 vs <50, HR=1.88 [95% CI 1.43, 2.48]), and
the geographical region of Asia (Asia vs USA+Canada, HR=1.86 [95% CI 1.30, 2.66]).4
Zoster Virus Reactivation
Herpes zoster, or shingles, is caused by the reactivation of varicella zoster virus. Risk factors for varicella zoster virus reactivation include older age and a compromised immune system.5
Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster, herpes simplex), were reported in clinical studies. Herpes zoster was reported more commonly in patients ≥ 65 years of age who had previously been treated with both biologic and conventional DMARDs. If a patient develops herpes zoster, baricitinib treatment should be temporarily interrupted until the episode resolves.1
Follow Local Guidance When Administering Vaccines
No data are available on the response to vaccination with live vaccines in patients receiving baricitinib. Use with live, attenuated vaccines during, or immediately prior to, baricitinib therapy is not recommended. Prior to initiating baricitinib, it is recommended that all patients be brought up to date with all immunisations in agreement with current immunisation guidelines.1
For further information please refer to "EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases" available on the EULAR website.6
No information is available regarding the use of BARI with a non-live HZ vaccine because
non-live HZ vaccine was not available at the time of the RA phase 3 studies, and
2. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 7 years: an updated integrated safety analysis. Presented as an oral presentation at: European League Against Rheumatism (EULAR) Annual Meeting; June 12-15, 2019; Madrid, Spain.
3. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 7 years: an updated integrated safety analysis. Ann Rheum Dis. 2019;78(2):308-309. http://dx.doi.org/10.1136/annrheumdis-2019-eular.691
4. Chen YH, Chen YM, Smolen J, et al. Incidence rate and characterisation of herpes zoster events in patients with moderate to severe rheumatoid arthritis: an update from baricitinib clinical trials. Poster presented at: European League Against Rheumatism (EULAR) Annual Meeting; June 12-15, 2019; Madrid, Spain.
5. Schub D, Janssen E, Leyking S, et al. Altered phenotype and functionality of varicella zoster virus-specific cellular immunity in individuals with active infection. J Infect Dis. 2015;211(4):600-612. http://dx.doi.org/10.1093/infdis/jiu500
6. EULAR.org [Internet] van Assen S et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2011;70:414-422. doi:10.1136/ard.2010.137216 [online] 2010. [cited 2017 Dec 18]. Available from: http://www.eular.org/recommendations_management.cfm http://www.eular.org/recommendations_management.cfm
BARI = baricitinib
DMARD = disease-modifying antirheumatic drug
HZ = herpes zoster
IR = incidence rate
MTX = methotrexate
PY(s) = patient year(s)
PYE = patient-years of exposure
RA = rheumatoid arthritis
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Datum fӧr senaste ӧversyn 2019 M02 22