A Deep Dive Into Combination Therapy

On the 2nd day of the 9th Interdisciplinary Autoimmune Summit, Joseph Merola, MD, MMSc, and Adam Cheifetz, MD, presented their discussion-based session, “Deep Dive: Combination Therapy Approaches.” Dr Merola kicked off the discussion by saying, “We’re here to tell you our anecdotes.”

Dr Merola described the case of a mutual patient of his and Dr Cheifetz, “One of the scenarios that really highlights combination therapy is the patient [who is] infliximab dependent…who develops a significant enough TNF-induced psoriasis… In the end, we went with the IL-12/23… We went for just [every] 12 weeks skin dosing, weight based though, which is 90 mg not the 45 mg… He’s done brilliantly well [and] he’s thrilled his skin is clear.”

He continued, “One of the other [scenarios] I find tricky is the patient who has axial disease, whether it’s axial spondyloarthritis or axial psoriatic arthritis with inflammatory bowel disease and either gets TNF-induced psoriasis or fails a TNF… One of the places we’ve come together is in a combination approach if need be.”

Dr Merola asked Dr Cheifetz to talk about the sphingosine l-phosphate receptor modulator ozanimod. “It’s approved for moderate to severe ulcerative colitis [and] is pretty safe… I think the biggest risk is infection,” Dr Cheifetz responded. He added, “I think your JAKs are going to be potentially more effective [and] they work very quickly.”

Dr Merola and Dr Cheifetz then discussed an attendee question: “Do we need to be thinking any differently about our hydroxychloroquine recommendations around, in particular, the EKG changes and QTc prolongation?” Their response was that for patients taking the medication long term, it does not hurt to get an EKG or an echo, especially if they are symptomatic.

The discussion then moved to current studies. “We’re going to have more data. There is an ongoing study in the psoriatic arthritis space to hopefully answer some of this question about combination therapy,” stated Dr Merola. He continued, “The question of safety will continue, but I would love to have that flexibility…to be more creative as we get more and more tools in the toolbox.”

Dr Cheifetz added, “The ultimate is to predict ahead of time response to certain agents.”

They concluded with their thoughts for the future of combination therapy. “I think it’s going to be absolutely an evolving area for all of us in the IMID space and we’re going to be seeing more data… I’m hoping we can do this in a more data-driven than anecdotal way in the future,” Dr Merola remarked. Dr Cheifetz agreed, “I’m hoping gone are the days of placebo-controlled trials…in uncontrolled diseases… We should be doing comparative effectiveness studies…head-to-head trials or combination…two different agents versus the combination and looking short term [and] long term. I think that’s where all the fields need to be heading, in addition to personalization, trying to figure out who is going to respond to what medications.”

Reference

Merola JF, Cheifetz AS. Deep dive: combination therapy approaches. Presented at: Interdisciplinary Autoimmune Summit; April 21–24, 2022; Virtual.