Acceptable Safety Profile of Upadacitinib for Moderate to Severe Rheumatoid Arthritis

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Upadacitinib was found to have a safety profile comparable with that of other JAK inhibitors used for the treatment of rheumatoid arthritis.

Upadacitinib was found to have a safety profile comparable with that of other Janus kinase (JAK) inhibitors used for the treatment of rheumatoid arthritis (RA), according to study results published in Annals of the Rheumatic Diseases.

Upadacitinib (15 mg once daily) is approved for patients with moderate to severe active RA who are intolerant or have an inadequate response to methotrexate.

As JAK inhibitors have been associated with several safety risks, including herpes zoster, serious and opportunistic infections, thromboembolic events and changes in laboratory parameters, the objective of the current integrated analysis was to determine the safety profile of upadacitinib based on data from 5 randomized controlled trials which comprised the phase III SELECT clinical programme.

Data on treatment-emergent adverse events and laboratory data from the SELECT-NEXT, SELECT-BEYOND, SELECT-MONOTHERAPY, SELECT-COMPARE and SELECT-EARLY trials ( Identifiers: NCT02675426; NCT02706847; NCT02706951; NCT02629159; and NCT02706873, respectively) were collected and analyzed. Depending on the study, subjects were treated with upadacitinib (15 or 30 mg once daily), placebo, methotrexate or subcutaneous adalimumab, as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs.

The cohort included 3834 patients who received at least 1 dose of upadacitinib across studies, including 2630 patients (79.9% women; mean age, 54.1 years) treated with upadacitinib 15 mg once daily, and 1204 patients (78.7% women; mean age, 55.3 years) treated with 30 mg once daily (4020.1 patient-years of exposure). A total of 579 patients were treated with adalimumab, 530 received methotrexate, and 1042 were given placebo.

There were 295.7 and 368.7 treatment-emergent adverse event per 100 patient-years with upadacitinib 15 mg and 30 mg, respectively, compared with 294.8 and 321.7 events per 100 patient-years with adalimumab and methotrexate, respectively.

The most common treatment-emergent adverse events with upadacitinib included upper respiratory tract infection, nasopharyngitis and urinary tract infection. Serious infections were more common with upadacitinib than with methotrexate, but similar to rates reported in patients treated with adalimumab.

Occurrence of herpes zoster and elevated levels of creatine phosphokinase were more common in patients receiving adalimumab and upadacitinib vs methotrexate. Treatment with upadacitinib was associated with a greater risk for gastrointestinal perforation (9 potential cases with upadacitinib, and no events with adalimumab, methotrexate, or placebo).

No difference was reported across treatment groups with regards to mortality risk, rates of malignancies, venous thromboembolism, or major adverse cardiovascular events.

“Based on an integrated analysis of the SELECT clinical trial programme, the overall safety profile of upadacitinib appeared comparable with other [JAK inhibitors], with no new or unexpected safety risks identified,” concluded the researchers.

Disclosure: This clinical trial was supported by AbbVie. Please see the original reference for a full list of authors’ disclosures.


Cohen SB, van Vollenhoven RF, Winthrop KL, et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme (published online Oct 28, 2020). Ann Rheum Dis. doi: 10.1136/annrheumdis-2020-218510