Olumiant® ▼ (baricitinib): Incidens av Herpes Simplex i RA kliniska utvecklingsprogram

Incidence of Herpes Simplex in the Rheumatoid Arthritis Clinical Development Program

Herpes simplex is a cluster of the MedDRA preferred terms of herpes simplex, oral herpes, eczema herpeticum, Kaposi's varicelliform eruption, ophthalmic herpes simplex, genital herpes, and genital herpes simplex.¹

Treatment-Emergent Adverse Events

A TEAE is an adverse event that either occurred or worsened in severity after the first dose of study treatment and did not necessarily have a causal relationship to study treatment.¹

7-Study Placebo-Controlled Dataset

Dataset Description

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 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

• 24 weeks of assigned treatment or until rescue in phase 3 studies.²

Data from BARI 2 mg (N=479, PYE=185.8) were 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

Incidence of Herpes Simplex

In this safety analysis, through 24 weeks of treatment, the TEAE of

• herpes simplex was reported in

  • 24 (2.1%) patients in the BARI 4 mg group

  • 6 (1.3%) patients in the BARI 2 mg group, and

  • 10 (0.8%) patients in the placebo group.¹

All Baricitinib Rheumatoid Arthritis Dataset

Dataset Description

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, and RA-BALANCE). Data includes a long-term extension study (RA-BEYOND) with

• 13,148 PYE

• median exposure of 4.2 years

• maximum exposure of 8.4 years, and

• data through September 1, 2019.^3,4

Incidence of Herpes Simplex

In the All BARI RA analysis set through September 1, 2019, a TEAE of

• herpes simplex was reported in 157 (4.2%) patients.¹

Of these 157 TEAEs of herpes simplex, 

• 2 were reported as serious adverse events

• 33 resulted in temporary interruption of BARI, and

• 9 resulted in permanent discontinuation of BARI.¹

Information from the Label

Baricitinib is associated with an increased rate of infections such as upper respiratory tract infections compared to placebo. In treatment naïve patients, combination with methotrexate resulted in increased frequency of infections compared to baricitinib monotherapy.⁵

The risks and benefits of treatment with baricitinib should be carefully considered prior to initiating therapy in patients with active, chronic or recurrent infections.⁵

If an infection develops, the patient should be monitored carefully and baricitinib therapy should be temporarily interrupted if the patient is not responding to standard therapy. Baricitinib treatment should not be resumed until the infection resolves.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.⁵

If a patient develops herpes zoster, baricitinib treatment should be temporarily interrupted until the episode resolves.⁵

In BARI clinical trials for up to 16 weeks, herpes simplex was commonly reported (≥1% and <10%).

Reporting rates for baricitinib compared to placebo for the infection-related herpes simplex were (1.8 % vs. 0.7 %).⁵

References

1. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

2. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis over a median of 3 years of treatment: an updated integrated safety analysis. Lancet Rheumatol. 2020;2(6):E347-E357. https://doi.org/10.1016/S2665-9913(20)30032-1

3. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 8.4 years: an updated integrated safety analysis [abstract]. Ann Rheum Dis. 2020;79(suppl 1):638. https://ard.bmj.com/content/79/Suppl_1/642.1

4. Genovese MC, Smolen JS, Takeuchi T, et al. Safety profile of baricitinib for the treatment of rheumatoid arthritis up to 8.4 years: an updated integrated safety analysis. Poster presented at: European League Against Rheumatism Virtual Congress; June 3-6, 2020.

5. Olumiant [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

Glossary

BARI = baricitinib

DMARD = disease-modifying antirheumatic drug

MedDRA = Medical Dictionary for Regulatory Activities

MTX = methotrexate

PYE = patient-years of exposure

RA = rheumatoid arthritis

TEAE = treatment-emergent adverse event

▼ 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.