Upadacitinib demonstrated significantly greater rates of skin clearance improvement and itch reduction compared to dupilumab at 16 weeks.

AbbVie’s JAK Inhibitor Rinvoq (upadacitinib) performed better than Dupixent (dupilumab) for primary and all ranked secondary endpoints in a phase 3b head-to-head study in adults with atopic dermatitis (AD), according to a new study in JAMA Dermatology.

Rinvoq is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. In human cellular assays, Rinvoq preferentially inhibits signaling by JAK1 or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2. 

Use of Rinvoq in moderate to severe atopic dermatitis is not approved and its safety and efficacy are under evaluation by the FDA and the EMA. In June 2021, the EMA's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the approval of Rinvoq for the treatment of moderate to severe atopic dermatitis.

The study expands upon previously announced topline results and showed upadacitinib (30 mg, once daily) achieved superiority compared to dupilumab for the primary endpoint, the proportion of patients with at least a 75 percent improvement in the Eczema Severity Index (EASI 75) at week 16.  Of those treated with upadacitinib, 71 percent achieved EASI 75 at week 16 compared to 61 percent of those treated with dupilumab, the study showed.  Additionally, upadacitinib demonstrated statistically significant greater efficacy across all ranked secondary endpoints compared to dupilumab through week 16, including early reduction in itch and rates of skin clearance improvement.

"In this study, upadacitinib 30 mg demonstrated a more rapid onset of action compared to dupilumab, with patients experiencing a reduction in itch at one week and skin clearance improvements at two weeks. In addition, more upadacitinib-treated patients achieved high levels of skin clearance, such as EASI 90 and 100, by 16 weeks of treatment," says Andrew Blauvelt, MD, MBA, lead investigator for the Heads Up study and president of Oregon Medical Research Center in Portland, Oregon,  in a news release.  "The results from this important comparative study will help inform how physicians work with their patients to set treatment goals for atopic dermatitis."

After one week of treatment, the upadacitinib 30 mg treatment group had a 31 percent reduction in itch (as measured by Worst Pruritus Numerical Rating Scale [NRS]) compared to 9 percent in the dupilumab group (p<0.001).

After two weeks of treatment, 44 percent receiving upadacitinib achieved EASI 75 versus 18 percent receiving dupilumab (p<0.001). 

At 16 weeks, 28 percent of people treated with upadacitinib achieved clear skin (EASI 100; p<0.001) and 61 percent achieved almost clear skin (EASI 90; p<0.001), compared to 8 percent and 39 percent, respectively, of those treated with dupilumab.

The safety profile of upadacitinib was consistent with what was observed in the Phase 3 pivotal studies, Measure Up 1, Measure Up 2 and AD Up.1-3 Through week 16, the most common adverse events were acne for the upadacitinib group and conjunctivitis for the dupilumab group.1 Serious adverse events occurred in 2.9 percent of those receiving upadacitinib and 1.2 percent of those receiving dupilumab. Serious infections were reported infrequently in both treatment groups (1.1 percent in those who received upadacitinib and 0.6 percent in those who received dupilumab). One treatment-emergent death due to bronchopneumonia associated with influenza A occurred in a patient who received upadacitinib. No malignancies were reported in the upadacitinib group; one non-melanoma skin cancer was reported in the dupilumab group. No major adverse cardiac events or venous thromboembolic events were reported in either treatment group.

About Heads Up

Heads Up is a Phase 3b multicenter, randomized, double-blind, double-dummy, active comparator-controlled study in adults with moderate to severe atopic dermatitis. Patients were randomized to receive upadacitinib (30 mg, once daily, orally administered) or dupilumab (300 mg, every other week, subcutaneous injection) for 24 weeks. Patients who received dupilumab received an initial dose of 600 mg at the baseline visit followed by 300 mg every other week. All patients received placebo of the other treatment as part of the Heads Up double-dummy study design.

The primary endpoint was the proportion of patients achieving EASI 75 at week 16. Ranked secondary endpoints were percent change from baseline in Worst Pruritus NRS (weekly average) at weeks 1, 4 and 16; proportion of patients achieving EASI 100 and EASI 90 at week 16; proportion of patients achieving EASI 75 at week 2; and Worst Pruritus NRS (weekly average) improvement ≥4 at week 16. Additional endpoints at week 24 included EASI 75, EASI 90, EASI 100 and improvement from baseline Worst Pruritus NRS (weekly average). More information on this trial can be found at www.clinicaltrials.gov (NCT03738397).