Transcript Related Guidelines

Decision Strategies in PsA Management: Role of JAK Inhibitors

Eric M. Ruderman, MD · Northwestern University

Disclosures

February 08, 2022

Editor’s Note: The U.S. Food and Drug Administration is requiring updated warnings for the JAK inhibitors tofacatinib, baricitinib, and upadacitinib, based on the results of a randomized clinical safety trial which indicated an increased risk of heart attack, stroke, blood clots, cancer and death attached to their use in patients with psoriatic arthritis, rheumatoid arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis.[1]

The U.S. Food and Drug Administration has approved a 15-mg extended release tablet of the Janus kinase inhibitor upadacitinib for patients with psoriatic arthritis who had an inadequate response or intolerance to one or more anti-tumor necrosis factor drugs based on the results of two phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2.[2]

Key Takeaways:

  • Janus kinase (JAK) inhibitors are oral agents that offer effectiveness comparable to biologics  

  • Two JAK inhibitors, tofacitinib and upadacitinib, are available for use in the treatment of psoriatic arthritis (PsA)

  • Tofacitinib does not seem to be as effective as biologics for treating skin disease, although it was shown to be effective for joint disease. For patients with mild skin disease, tofacitinib may be an appropriate alternative 

  • Upadacitinib seems effective for the treatment of both joint and skin disease

  • Both tofacitinib and upadacitinib have been shown to be effective for ankylosing spondylitis in controlled blinded clinical studies, and the agents are likely to be effective for axial disease and PsA

  • It is prudent to vaccinate patients who will be treated with a JAK inhibitor for herpes zoster, either before or shortly after they start the JAK inhibitor

  • Caution is warranted when considering use of a JAK inhibitor to treat psoriatic disease in patients at otherwise high risk or with a history of a venous thromboembolic event

This transcript has been edited for clarity.

We’ve been waiting a long time in rheumatology for oral agents that offer effectiveness comparable to the biologics we’ve been using for the past 20 years, and the appeal would be a drug that does not have to be given parenterally, either as a self-injection or as an intravenous infusion. We first saw these with the advent of JAK inhibitors. First tofacitinib, and then baricitinib, and, most recently, upadacitinib in rheumatoid arthritis. And now, at least two of these agents are coming to be available for use in psoriatic arthritis. Tofacitinib was approved about 2 years ago based on two pivotal phase 3 clinical trials. Similarly, two phase 3 clinical trials with upadacitinib have been reported, and the drug is currently under review at the FDA for this indication. 

One of the caveats with tofacitinib in the clinical trials was that it did not seem to be as effective for skin disease as the biologics, though it was quite effective for joint disease.[3] That has led to some concern about using that agent in patients with significant skin disease. In patients with mild skin disease that really isn’t driving therapy, it may be an appropriate alternative. 

Upadacitinib, on the other hand, seemed to be quite effective for skin disease in the clinical trials.[4] In fact, in the one trial in which adalimumab was used as a positive control, upadacitinib was about as effective as adalimumab for both skin and joint disease.[5] So, with the benefit for both joints and skin disease in clinical trials, upadacitinib seems to offer a reasonable option for patients with psoriatic disease. 

Tofacitinib may be [a reasonable option] as well, but probably for the patients with less skin disease, given the decreased effect of that drug for skin disease.[3,6] I should note that both tofacitinib and upadacitinib have been shown to be effective for ankylosing spondylitis in controlled blinded clinical studies, and both actually may ultimately be approved for this indication.[7] So, by extrapolation, they’re likely to be effective for axial disease and psoriatic arthritis. 

A couple of safety issues just to note to wrap things up on these JAK inhibitors: Number one, in terms of infection or infectious-type adverse events, herpes zoster has been shown to be more of an issue with JAK inhibitors than with biologic therapies, so it’s something to be on the lookout for in patients potentially otherwise at risk for [herpes] zoster.[8] It is certainly safe to use the current [herpes] zoster vaccine. I think in most cases, it would be prudent to think about vaccinating patients who are going to be treated with a JAK inhibitor for [herpes] zoster, either before or shortly after they start the JAK inhibitor. 

The other thing to be noted is that some recent concerns have been raised about the potential for venous thromboembolic events in patients treated with JAK inhibitors. Psoriatic arthritis patients are certainly at risk for this. We still don’t have the final answer on how significant this risk is and whether it’s different from one JAK inhibitor to another, but I think caution is probably warranted in patients who are at otherwise high risk or perhaps have had a history of a venous thromboembolic event when considering use of a JAK inhibitor to treat psoriatic disease. 

 

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