Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 years and up to 3.9 years of treatment: an updated integrated analysis of eight clinical trials

Abstract

Background

Baricitinib, a selective Janus kinase (JAK)1/JAK2 inhibitor, is approved for treatment of moderate-to-severe atopic dermatitis (AD) in adults.

Objectives

We report integrated baricitinib safety data in patients with up to 3.9-years exposure.

Methods

Three datasets from the integrated AD clinical trial program were analyzed: placebo-controlled, 2-mg–4-mg extended, and All-bari. Data cutoffs were up to 21-December-2021 for long-term extension studies. Proportions of patients with events and incidence rates (IR)/100 patient years (PY) at risk were calculated.

Results

2636 patients received baricitinib for 4628.4 PY. Discontinuation due to adverse events was low (IR = 3.4). IRs in All-bari were: serious adverse events, 5.2; infection, 67.2 (any infection), 6.7 (herpes simplex), 2.8 (herpes zoster), and 0.3 (opportunistic infections). Adverse events of special interest in All-bari included seven patients with positively adjudicated major adverse cardiovascular events (MACE) (IR = 0.15), three pulmonary emboli (PE) (IR = 0.06), 14 malignancies excluding nonmelanoma skin cancer (IR = 0.3), one gastrointestinal perforation (IR = 0.02), and four deaths (IR = 0.1). No deep vein thromboses (DVT) or tuberculosis were reported.

Conclusion

In this analysis, baricitinib maintained a similar safety profile to earlier analyses with no new safety signals. Rates of MACE, DVT/PE, malignancies, and serious infections were within ranges of background rates in patients with AD.

Clinicaltrials.gov

NCT02576938 (JAHG), NCT03334396 (JAHL; BREEZE-AD1), NCT03334422 (JAHM; BREEZE-AD2), NCT03334435 (JAHN; BREEZE-AD3), NCT03428100 (JAIN; BREEZE-AD4), NCT03435081 (JAIW; BREEZE-AD5), NCT03559270 (JAIX; BREEZE-AD6), NCT03733301 (JAIY; BREEZE-AD7)

Keywords:

• Atopic dermatitis
• long-term safety
• baricitinib

Acknowledgements

The authors thank the investigators and patients who have participated in the baricitinib atopic dermatitis clinical trial program. The authors also like to acknowledge Kathy Oneacre, MA (Syneos Health, Morrisville, NC, USA) who provided medical writing support and Antonia Baldo (Syneos Health, Morrisville, NC, USA) who provided editing support that was funded by Eli Lilly and Company.

Disclosure statement

Thomas Bieber reports personal fees from Eli Lilly and Company during the conduct of the study; personal fees from AbbVie, Affibody, Almirall, AnaptysBio, Arena Pharma, Asana BioSciences, ASLAN Pharma, Bayer Health, BioVersys, Böehringer Ingelheim, Bristol-Myers Squibb, Connect Pharma, Dermavant, Domain Therapeutics, Eli Lilly and Company, EQRx, Galderma, Glenmark, GSK, Incyte, Innovaderm, IQVIA, Janssen, Kirin, Kymab, LEO, LG Chem, L’Oréal, MSD, Novartis, Numab, OM Pharma, Pfizer, Pierre Fabre, Q32bio, RAPT, Sanofi/Regeneron, UCB Pfizer, Bayer, AbbVie, Sanofi-Genzyme, LEO, Galapagos, Glenmark, Galderma, Almirall, AnaptysBio, Arena Pharma, Asana BioSciences, Boehringer Ingelheim, Dermavant, Incyte, Kymab, Menlo, Novartis, and UCB outside the submitted work.

Norito Katoh reports grants and personal fees from AbbVie, Eli Lilly Japan, Janssen, Kyowa Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe Pharma, Sanofi, Taiho Pharmaceutical, and Torii Pharamacuetical; personal fees from Celgene Japan; grants from A2 Healthcare, Eisai, and Sun Pharma outside the submitted work.

Eric Simpson reports grants and personal fees from AbbVie, Eli Lilly and Company, LEO Pharmaceutical, Medimmune, Pfizer, Regeneron; grants from Celgene, Galderma, Kyowa Hakko Kirin, Merck, Novartis, Tioga; personal fees from Boehringer Ingelheim, Dermavant, Dermira, Forte Bio, Incyte, Menlo Therapeutics, Ortho Dermatologics, Pierre Fabre Dermo Cosmetique, Sanofi, Valeant.

Marjolein de Bruin-Weller reports grants and personal fees from AbbVie, Almirall, Eli Lilly and Company, Galderma, Pfizer, Regeneron, Sanofi-Genzyme, and UCB outside the submitted work.

Diamant Thaci reports personal fees from AbbVie, Almirall, Amgen, Asana Biosciences, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Novartis, Regeneron, Sandoz, Sanofi-Aventis, Pfizer, and UCB and grants from AbbVie, LEO Pharma, and Novartis during the conduct of the study.

Antonio Torrelo reports other from Eli Lilly and Company during the conduct of the study; other from AbbVie, Novartis, Pfizer, Pierre Fabre, and Sanofi outside the submitted work.

Angelina Sontag, Susanne Grond, Maher Issa, Tracy Cardillo, and Katrin Holzwarth are employees and stockholders with Eli Lilly and Company

Xiaoyu Lu has no conflicts to report.

Jacob P Thyssen is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, ASLAN Pharmaceuticals, Coloplast, Eli Lilly and Company, LEO Pharma, OM Pharma, Union Therapeutics, Pfizer, Regeneron, and Sanofi-Genzyme, a speaker for AbbVie, Almirall, Eli Lilly and Company, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, and received research grants from Pfizer, Regeneron, and Sanofi-Genzyme.

Data availability statement

Eli Lilly and Company provides access to all individual participant data collected during the trial, after anonymization, with the exception of pharmacokinetic or genetic data. Data are available to request 6 months after the indication studied has been approved in the United States and the European Union and after primary publication acceptance, whichever is later. No expiration date of data requests is currently set once data are made available. Access is provided after a proposal has been approved by an independent review committee identified for this purpose and after receipt of a signed data sharing agreement. Data and documents, including the study protocol, statistical analysis plan, clinical study report, and blank or annotated case report forms, will be provided in a secure data sharing environment. For details on submitting a request, see the instructions provided at www.vivli.org.

Additional information

Funding

This study was designed jointly by consultant experts and representatives of the funder, Eli Lilly and Company. Data were collected by investigators and analyzed by the funder. Safety data were reviewed at regular intervals by an independent data monitoring committee. All authors participated in the data analysis or interpretation, drafting, and critical review of the manuscript, and provided final approval for the publication of the manuscript. The authors had full access to the data and verified the veracity, accuracy, and completeness of the data and analyses as well as the fidelity of this report to the protocol. All authors made the decision to submit the manuscript for publication. Baricitinib is developed by Eli Lilly and Company, under license from Incyte Corporation.