Gerd Burmester, MD: Long-Term Data Supports Upadacitinib's Safety in Rheumatic Disease Treatment

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Gerd Burmester, MD, discusses the favorable long-term safety data of upadacitinib treatment across rheumatic diseases.

In an interview with HCPLive, Gerd Burmester, MD, professor of medicine in the Department of Rheumatology and Clinical Immunology at the Charité University Hospital, Free University of Berlin, and Humboldt University of Berlin, Germany, discusses the results of a study analyzing the long-term safety of upadacitinib treatment among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA)ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA).1

A team of investigators led by Burmester used data from the SELECT clinical program, including 11 phase 3 upadacitinib trials. A total of 4998 patients (RA, n = 3209; PsA, n = 907; AS, n = 596; nr-axSpA, n = 286) received ≥ 1 dose of upadacitinib 15 mg, totaling 15,895.8 patient-years of exposure. The majority of exposure was derived from RA studies. 1

“Safety observed with Janus kinase (JAK) inhibition to date has highlighted the need to further characterize the long-term safety profile of individual JAK inhibitors across diverse patient populations,” the team wrote.1

Results revealed the rates of treatment-emergent adverse events were generally comparable between upadacitinib 15 mg and the active comparators (adalimumab and methotrexate) in both RA and PsA, with the exception of serious infections (in PsA), herpes zoster, and non-melanoma skin cancer. Elevated creatine phosphokinase was also observed among some patients receiving upadacitinib, although it was not clinically meaningful.1

Although adverse events leading to discontinuation in the upadacitinib cohort varied, they were generally similar across treatment groups and diseases. The most common adverse events were pneumonia (RA; n = 22/459), COVID-19 (PsA; n = 7/121), headache (AS; n = 3/42), and worsening axial spondyloarthritis and pulmonary embolism (nr-axSpA; both n = 2/20).1

Across the rheumatic diseases included in the analysis, upadacitinib 15 mg demonstrated a generally consistent safety profile with no new safety risks identified with long-term treatment.1

What inspired the team to evaluate the long-term safety profile of upadacitinib among patients with rheumatic disease?

Gerd Burmester, MD: The study on "Safety of Upadacitinib Across Rheumatoid Arthritis, Psoriatic Arthritis, and Axial Spondyloarthritis Encompassing 15,000 Patient-Years of Clinical Trial Data" recently presented at the 2024 European Congress of Rheumatology (EULAR)was triggered in many parts by questions surrounding the safety of JAK inhibition not only in RA but other important inflammatory joint conditions as well. Here, large patient populations and long observation periods are necessary, which we accomplished with our investigation.

Were these results surprising?

GB: In the eyes of the investigators, it is reassuring that no surprises regarding the safety profile of upadacitinib were detected. In all analyses, the safety profile remained constant.

In your opinion, what is the clinical significance of these findings?

GB: These data show along with other findings that upadacitinib has a favourable risk/benefit profile, especially compared to the "standard" comparators adalimumab and methotrexate.

Does the team plan on doing any further research on this topic?

GB: Yes, we will continue this work with longer follow up periods and additional patient populations.

Are there any other key takeaways that you'd like our audience to know?

GB: It will be important to compare and further contextualize these data to real world evidence such as the JAK-pot study investigating many registries, especially for diseases with more limited clinical trial exposure (eg, AS and nr-axSpA).

Note: The JAK-pot study assessed the rate of treatment discontinuation due to adverse events of JAK inhibitors and biologic disease-modifying antirheumatic drugs (bDMARDs) among a cohort of patients with RA using 17 registers and more than 46,000 treatment courses. Results demonstrated JAK inhibitors were not linked to a greater rate of discontinuations for adverse events. However, higher rates were observed in patients receiving tofacitinib and in those aged ≥ 65 years.3


  1. Burmester GR, Cohen SB, Deodhar A, Mysler E, et al. Safety of Upadacitinib Across Rheumatoid Arthritis, Psoriatic Arthritis, and Axial Spondyloarthritis Encompassing 15,000 Patient-Years of Clinical Trial Data. Presented at: EULAR. Vienna, Austria. June 12 – 15, 2024.
  2. Kunzmann, K. FDA Approves Upadacitinib for Inadequately Treated Rheumatoid Arthritis. HCPLive. August 16, 2019. Accessed July 10, 2024.
  3. Aymon R, Mongin D, Bergstra SA, et al. Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study). Ann Rheum Dis. 2024;83(4):421-428. Published 2024 Mar 12. doi:10.1136/ard-2023-224670