American College of Rheumatology Releases Statement on FDA Revisions to Janus Kinase Inhibitor Boxed Warning

AUA updated renal mass guidelines.
AUA updated renal mass guidelines.
The American College of Rheumatology released a statement in light of the FDA revisions to the Janus kinase inhibitor Boxed Warning.

The American College of Rheumatology (ACR) recently issued a statement to address the US Food and Drug Administration (FDA) revisions to the Boxed Warning for Janus kinase (JAK) inhibitors. The full statement is available on the ACR website.

On September 1, 2021, the FDA announced required revisions to the Boxed Warning for JAK inhibitors, including those that have been approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), polyarticular-course juvenile idiopathic arthritis (pcJIA), and ankylosing spondylitis (AS). The revised warning is to include information regarding the risks for serious heart-related events, cancer, blood clots, and death that have been reported with the use of JAK inhibitors.

The JAK inhibitors are currently approved for patients with an inadequate or intolerant response to 1 or more tumor necrosis factor (TNF) inhibitors (adalimumab or etanercept). Currently, the JAK inhibitors include tofacitinib, baricitinib, and upadacitinib — all of which are targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs).

The effect of tofacitinib on cardiovascular (CV) events was shown in the ORAL Surveillance study ( Identifier: NCT02092467) that was conducted among patients older than 50 years with RA and 1 or more additional CV risk factors. However, the FDA cited a similar mechanism of action with the other JAK inhibitors as well, thus broadening the revised indication to include all JAK inhibitors used in RA, PsA, pcJIA, and AS populations. These data were officially published on January 27, 2022.

According to published data, an increased risk for major adverse CV events (MACE), malignancy, thrombotic events, and mortality was reported among patients who received treatment with tofacitinib compared with those who received TNF inhibitor therapy. The MACEs included all fatal CV events, nonfatal myocardial infarction, and nonfatal cerebrovascular accident. Patients considered at higher risk were smokers, men, individuals older than 65 years, and those who had previous CV events, stroke, or malignancy (other than a successfully treated nonmelanoma skin cancer).

In their statement, the ACR Janus Kinase Inhibitor Task Force noted that shared decision-making between patients and health care providers was recommended with regard to the risk-benefit profile of JAK inhibitor therapy as a potential treatment consideration for patients among whom continued use of TNF inhibitor therapy may be not feasible.


Snow M, Beall A, Goodman SD, et al; Janus Kinase Inhibitor Task Force. Janus Kinase inhibitor boxed warning. Statement for the American College of Rheumatology. Updated January 28, 2022. Accessed February 14, 2022.