Researchers of a recent systematic review and meta-analysis examine how dupilumab compares to older systemic treatments for atopic dermatitis, including methotrexate, cyclosporine and azathioprine.
A recent systematic review and meta-analysis shows that dupilumab and cyclosporine may outperform methotrexate and azathioprine in adults with atopic dermatitis (AD) treated for up to 16 weeks.
“We know from many well-done trials that dupilumab is better than placebo,” says co-author Aaron Drucker, M.D., ScM. He is a clinician scientist, Division of Dermatology, at Women’s College Hospital and Women’s College Research Institute and assistant professor, Department of Medicine, at the University of Toronto. The study was published online April 22 in JAMA Dermatology.
However, says Dr. Drucker, no randomized trials compare dupilumab with older systemic treatments including methotrexate, cyclosporine and azathioprine, and few trials show how these older treatments compare with each other.
“So while we can estimate from our data that it looks like dupilumab and cyclosporine are roughly equally effective, and better than methotrexate and azathioprine, which should be better than placebo, it’s still hard to make firm conclusions,” he adds.
Because only six studies reported outcomes beyond 16 weeks, investigators limited their analysis to this timeframe. With a mean reduction of 11.3 points (95% confidence interval, 9.7-13.1) on the Eczema Area and Severity Index (EASI), dupilumab 300 mg every two weeks was superior to placebo, with high certainty according toGrading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Investigational medications that also demonstrated EASI reductions versus placebo (moderate certainty in all analyses) included baricitinib 2 mg daily (5.6 points) and 4 mg daily (5.2 points) and tralokinumab 150 mg every two weeks (4.3 points) and 300 mg every two weeks (4.9 points).
In standardized mean difference (SMD) calculations, azathioprine, low- and high-dose cyclosporine, methotrexate and dupilumab had moderate or large benefits relative to placebo. Higher-dose cyclosporine (SMD, -1.1, low certainty) and dupilumab (SMD, -0.9, high certainty) appeared similarly effective versus placebo in clearing clinical signs of AD. These medications moreover may be superior to methotrexate (SMD, -0.6, low certainty) and azathioprine (SMD, -0.4, low certainty).
Additionally, dupilumab 300 mg every two weeks was associated with clinically relevant improvements in Patient-Oriented Eczema Measure (POEM, -7.5, high certainty) and Dermatology Life Quality Index (DLQI, -4.8, high certainty) scores.
Investigators analyzed 39 trials that included 6,360 patients total. Most trials (29) were industry-sponsored, and most comparisons were against placebo. Sixteen studies had at least one element at high risk of bias. But even in some newer studies with lower risk of blinding-associated bias, incomplete outcome data introduced potential bias.
Investigators were somewhat disappointed, says Dr. Drucker, that a relative dearth of reported adverse events prevented valid safety comparisons.
"Fortunately, a lot of that is due to the fact that in randomized, controlled trials for many of these medications, there aren't many serious adverse events," he notes.
For clinicians, Dr. Drucker adds, the study is helpful for putting the above treatments in context because until now, no valid comparisons using randomized, controlled data have existed.
"Even though our estimates aren't very precise, and there's a lot of uncertainty, we can at least help physicians with an estimate of how these treatments compare," he says.
Perhaps more importantly, Dr. Drucker and colleagues plan to update the meta-analysis every four months, posting the results to www.eczematherapies.com.
"We know that there are well-done trials coming for multiple new agents that hopefully in the next two years will be approved for atopic dermatitis," he says. "Once we can incorporate that data into our review on an ongoing basis, clinicians will be able to use our data to make comparisons between dupilumab and all these new treatments."
These comparisons likely will carry much more certainty, he adds, because development programs for some of these drugs, such as upadacitinib, include comparison trials against dupilumab.
Drucker AM, Ellis AG, Bohdanowicz MD, et al. Systemic immunomodulatory treatments for patients with atopic dermatitis: a systematic review and network meta-analysis. JAMA Dermatol. DOI: 10.1001/jamadermatol.2020.0796. Published online April 22, 2020.
Dr. Drucker has served as an investigator and received research funding from Sanofi and Regeneron. He has been a consultant for Sanofi and RTI Health Solutions, and his institution has received educational grants from Sanofi and AbbVie.