Dr. Merola also highlighted two head-to-head trials comparing IL-17i inhibitors (i.e., ixekizumab and secukinumab) to a tumor necrosis factor inhibitor (TNFi), adalimumab.7,8 “What you see at high level are very similar joint efficacy outcomes, but superior outcomes with the IL-17i for skin disease,” he noted. “So in a patient with severe skin and joint disease, I would absolutely consider using IL-17i as first-line biologics in lieu of TNFi.”
Combo Biologic Therapy?
Dr. Merola touched on the emerging idea of combination biologic therapy. “This isn’t something we routinely do,” he shared, “but I want to introduce this idea for really severe and refractory cases. Many of our newer agents offer more targeted mechanisms with favorable safety profiles that should allow us to consider this approach for patients in need.
“Our colleagues [who have patients with gastrointestinal disorders or inflammatory bowel disease (IBD)] are doing some interesting work in this area. In the recent VEGA study, patients with moderate to severe ulcerative colitis were treated with a combination of guselkumab (IL-23i) and golimumab (TNFi), compared with biologic monotherapy. Those on combination therapy achieved higher rates of clinical response, clinical remission and endoscopic improvement by week 12, with no obvious safety signal in early data.9
“Similar work is ongoing in this regard for PsA and will hopefully inform our ability to consider combination approaches in the future.10 We have several patients with TNF-inhibitor-dependent IBD who develop psoriasis, TNF-induced psoriasis, PsA and other conditions for whom we have had tremendous success adding anti-IL12/23 or anti-IL23 to their TNF inhibition.
“I’ve also treated a patient with a combination of IL-17i and a Janus kinase inhibitor who had variably failed every mechanism for skin vs. joint disease and has only been able to capture both with combination therapy. This is obviously a single case, and we had to counsel her at length about the possibility of severe infection and other potential for long term side effects, but she has seen great response and has regained her ability to work and function. We envision utility of combination therapy as potentially an ‘induction regimen’ for flare-based control or for those truly resistant cases.
“This might become more of a reality in our PsA patients in the future. … Sometimes, you have to kill two birds with two stones,” he concluded.
Samantha C. Shapiro, MD, is the executive editor of Harrison’s Principles of Internal Medi-cine. As a clinician educator, she practices telerheumatology and writes for both medical and lay audiences.
