IMID-JAK Pearls from Dr Ruth Ann Vleugels

At the Interdisciplinary Autoimmune Summit, Ruth Ann Vleugels, MD, MPH, MBA, presented “Strategies for Improving IMID Outcomes: The Potential of JAK Inhibitors,” sharing a number of pearls when it comes to utilizing Janus kinase (JAK) inhibitors for the treatment of immune-mediated inflammatory diseases (IMIDs).

JAK inhibitors have a growing application in rheumatology, dermatology, and gastroenterology as effective therapies for IMIDs. The current JAK inhibitors available and approved indications include

• Tofacitinib: rheumatoid arthritis (RA), psoriatic arthritis, ulcerative colitis, polyarticular juvenile idiopathic arthritis
• Baricitinib: RA
• Upadacitinib: RA

Further, JAK inhibitors have numerous clinical trials or case studies for efficacy in dermatomyositis, psoriasis, alopecia areata (AA), vitiligo, atopic dermatitis (AD), lupus, sclerosis, and sarcoidosis. Dr Vleugels highlighted many examples from the literature in between real case images from her practice.

When it comes to adverse events, JAK inhibitors do have some safety concerns. There is a clear signal for herpes zoster, to which providers should “consider adding a shingles vaccine or looking at varicella zoster virus titers,” said Dr Vleugels. Another serious concern is venous thromboembolic events, which may be a class effect for patients with RA, as the data are still limited in other diseases. Further, compared with TNF inhibitors, JAK inhibitors show consistently lower risks of tuberculosis reactivation and serious infection; however, there is increased concern regarding higher risk of malignancy, though more research is needed to better define the risks.

In the post-presentation Q&A with Mital Patel-Cohen, MD, Dr Patel-Cohen shared several audience questions regarding specific disease combinations, such as RA and lupus or AD and hidradenitis suppurativa. Dr Vleugels responded that JAK inhibitors can provide relief for patients with multiple comorbidities. This may be because of JAKs applying inhibition on a broader number of pathways, depending on its individual target (JAK1 vs JAK2 vs JAK3 vs TYK2).

In addition, when it comes to getting payer support and approval for JAK inhibitors, Dr Vleugels suggested paying attention to comorbid conditions, including mental health. Documentation of mental comorbidities or conditions that are currently FDA-approved indications (eg, RA with AA) can increase the likelihood of approval and coverage by an insurer.

However, as JAK inhibitors are still largely new therapeutic options, the current evidence in regard to safety should be heavily considered. Dr Patel-Cohen asked if there should be any concerns with clotting disorders, particularly in patients who have antiphospholipid syndrome. “Last year, I would’ve told you I was a little concerned but would just use caution through active testing and disease modifications,” said Dr Vleugels, “but recent data makes me a little more careful.” She added that she asks about family history of cardiovascular diseases and clotting disorders and smoking history, among others. Providers should follow complete blood count with differential, liver function tests, and cholesterol.

Reference
Vleugels RA. Strategies for Improving IMID Outcomes: The Potential of JAK Inhibitors. Presented at: Interdisciplinary Autoimmune Summit; April 15-18, 2021; virtual.