JAK inhibitors 'may prove useful' in wider range of immune-mediated inflammatory diseases
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Janus kinase inhibitors “may prove useful” in a wider range of immune-mediated inflammatory diseases, including refractory cutaneous dermatomyositis, chronic plaque psoriasis and other conditions, according to a speaker here.
“What I hope you’ll take away from this lecture is to really think about the treatment gaps we have using traditional DMARD and biologic therapies, and the role of JAK inhibitors to address these gaps,” Ruth Ann Vleugels, MD, MPH, MBA, director of the Autoimmune Skin Disease Program at Brigham and Women’s Hospital, told attendees at the 2021 Autoimmune Interdisciplinary Summit. “In addition, we want to look at the most current clinical data using JAK inhibitors, and also incorporate this into patient-centric approaches to caring for our patients using JAK inhibition.”
There are currently three JAK inhibitors approved by the FDA for IMIDs: tofacitinib (Xeljanz, Pfizer) for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and polyarticular juvenile idiopathic arthritis, as well as baricitinib (Olumiant, Eli Lilly & Co.) and upadacitinib (Rinvoq, AbbVie) for RA.
Meanwhile, several recent studies have explored their off-label use in a variety of conditions, Vleugels said.
“We’re going to start with a disease that I see very frequently in my clinics,” she said, presenting the first in a series of case studies. “This is a patient with refractory cutaneous dermatomyositis.”
The presented patient had failed multiple typical therapies for dermatomyositis, which, several years ago, led Vleugels to begin tofacitinib 10 mg twice per day. This regimen led to improvements in photodistributed erythema and other symptoms.
Vleugels and colleagues would also publish a case series in JAMA demonstrating improvements in refractory cutaneous dermatomyositis among patients treated with tofacitinib 10 mg twice daily.
“Back in 2016, we published the first series using JAK inhibition for dermatomyositis,” she said. “This was a small series, but we showed that the mean decrease in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) was 12. Now, a meaningful decrease in this score is actually 4 to 5, so this was quite a substantial improvement, and all of our patients had decreased itch.”
“Now, since 2016, I’ve had the opportunity to treat many additional patients,” Vleugels added. “This patient in particular was a Jehovah’s witness, and therefore is unable to take intravenous immunoglobulin, which is a therapy we frequently use for cutaneous dermatomyositis.”
In other case studies, Vleugels presented data that demonstrated similarly promising results for tofacitinib in patients with chronic plaque psoriasis, including a reversal of alopecia universalis in those with the disease.
However, many diseases warrant a higher dose than the typical RA regimen of 5 mg twice daily, necessitating a consideration of side effects.
“In the pediatric population, they reach the adult dose of tofacitinib — 5 mg twice a day — at just shy of 90 pounds, or 40 kg, and of course most of use are familiar with the fact that, given our earlier arthritis data, we know it’s safe to combine JAK inhibitors with methotrexate,” Vleugels said. “Also, of course, we need to think about adverse events.
According to Vleugels, JAK inhibitors carry a clear signal for shingles, leading her and her colleagues to consider the Shingrix (GlaxoSmithKline) zoster vaccine in adults patients specifically because it is a “kill vaccine,” and these patients are typically immunosuppressed.
There are also additional concerns that venous thromboembolism may be a class effect in JAK inhibitors, although Vleugels stated that the data on this is “somewhat lacking at this time.” Compared to TNF alpha inhibitors, researchers believe JAK inhibitors demonstrate lower risks for tuberculosis reactivation and serious infection, but with a higher potential risk for malignancy.
“Looking forward, JAK inhibitors may prove useful in an even wider array of conditions,” Vleugels said. “Currently, we have FDA approvals for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and polyarticular juvenile idiopathic arthritis. We know there is a clear signal for zoster in patients with JAK inhibition. We know there is an increased thromboembolism risk in patients treated with tofacitinib for rheumatoid arthritis.”
“However, so far, it’s unclear whether this risk corresponds in other populations as well,” she added. “We need longer-term data to assess and address that question. In addition, data in MACE outcomes and cancer risk are evolving rapidly, including in the last few months, and we will certainly learn more about this in the near future.”
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Vleugels RA. Strategies for Improving IMID Outcomes: The Potential of JAK Inhibitors. Presented at: Interdisciplinary Autoimmune Summit. April 15-18, 2021 (virtual meeting).
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