A Deep Dive Into Dual Targeting

On the first day of the 9th Interdisciplinary Autoimmune Summit, Stephen Hanauer, MD, FACG; Joel Gelfand, MD, MSCE; and Leonard Calabrese, DO, got together to discuss dual targeted therapy from the perspectives of gastroenterology, dermatology, and rheumatology, respectively, in their session “Deep Dive: Dual Targeting.”

The conversation started with whether patients who are on combination therapies and have achieved remission can stop one of their medications, such as methotrexate. Dr Hanauer remarked: “In patients who are on combination therapies, we do several things. Number one, [we] make certain they’re in as deep a remission as possible before we consider withdrawing one or the other. And then the second thing we do is we actually measure levels… Unfortunately, if they’re not in a remission, we don’t stop either [medication] in that situation. The question is, should we be adding something.”

On the topic of methotrexate, Dr Gelfand, added, “Methotrexate was actually one of the first drugs approved for psoriasis well over 50 years ago, so it was a workhorse for many years in dermatology for management of psoriatic disease. I think in the modern era, the issue is that our newer therapies, particularly the biologics, are so much more effective.”

The discussion turned to Janus kinase (JAK) inhibitors, with Dr Calabrese weighing in on current labeling, “The labeling has just changed for us this year… JAKs can only be used in people [who] have failed TNF inhibitors.” He stressed, “We consider JAK inhibitors [to be] an extraordinarily valuable class of drugs.”

Regarding the black box warnings for JAK inhibitors, Dr Gelfand stated, “Topical JAKs are approved for atopic dermatitis and that drug carries a black box warning about thrombosis, cancer, and everything else when using these drugs systemically… Someone gets home with a tube of something to put on their skin, they’re a little alarmed to see a black box warning.”

Dr Hanauer pointed out, “We know that active inflammation is a pro factor for cardiovascular disease and thrombosis… What we find is when you reduce inflammation, you reduce those risks.”

Continuing with a discussion of biologics, Dr Calabrese said, “The concept of multiple biologics is really in its infancy in our area… If I look at the clinical trial landscape, some of the most interesting drugs that are coming out are actually by specific antibodies.”

Dr Calabrese then brought up the risk of overtreatment, “Overtreatment can occur… We see in our referral practice lots of these patients who are treated to the point of toxicity for fatigue of noninflammatory origin, pain of noninflammatory origin, and the like.” Dr Gelfand added, “We don’t really have a lot of overtreatment issues on the dermatology side these days… The challenge we have is the end point. When do you decide to start tapering a biologic or increasing the duration and frequency?”

“The challenge we’ve had is that we’ve created targets that are unachievable,” Dr Hanauer stated. “I’m getting patients referred to me on their third biologic. They feel perfectly well, but the doc scopes them, and they still see an ulcer. And they say that they haven’t achieved their target, what’s next? And I quote the Rolling Stones, ‘You can’t always get what you want, you get what you need.’”

Bringing the discussion back around to combination therapy, Dr Hanauer summarized, “I think this concept of dual therapy really means do two mechanisms do better than one?”

Reference

Gelfand JM, Hanauer SB, Calabrese L. Deep dive: dual targeting. Presented at: Interdisciplinary Autoimmune Summit; April 21–24, 2022; Virtual.