麻豆传媒

More than half of patients with moderate-to-severe atopic dermatitis (AD) had complete or near-complete clearance after 12 weeks of oral treatment with an investigational Janus kinase 1 inhibitor, a preliminary study showed.

Overall, 54.3% of patients randomized to the higher of two doses of SHR0302 attained an Investigator Global Assessment (IGA) score of 0/1 as well as at least a two-point improvement from baseline. That compared with 5.7% of placebo-treated patients who had an IGA 0/1 status at 12 weeks. A lower dose of SHR0302 led to IGA 0/1 responses in 25.7% of patients.

Three fourths of patients in the high-dose arm had Eczema Area and Severity Index (EASI) 75 responses, and 45.7% had EASI 90 responses. Similar improvement occurred in itch severity, reported Jianzhong Zhang, MD, of Peking University People's Hospital in Beijing, during the virtual meeting.

"SHR0302 demonstrated significant efficacy in patients with moderate-to-severe atopic dermatitis," Zhang concluded. "SHR0302 showed fast control [within 1 week] of itching symptoms and was well tolerated. Phase III studies are warranted to confirm the safety and efficacy of SHR0320 in moderate-to-severe atopic dermatitis."

The study involved 105 patients with longstanding AD (9-11 years), associated with baseline IGA scores of 3-5, EASI scores of 25-30, and involvement of about 50% of body surface area. Patients were randomized to SHR0302 doses of 4 mg or 8 mg daily or to placebo. The primary endpoint was the proportion of patients who achieved IGA 0/1 status after 12 weeks of treatment.

Improved AD Outcomes with First-In-Class Drug

Patients with moderate/severe AD had significant improvement in physician- and patient-reported outcomes (PROs) at 12 weeks with the sphingosine 1-phosphate receptor (S1P₁) modulator etrasimod, according to a secondary analysis of a randomized trial.

Results showed that 29.8% of patients in the etrasimod 2 mg arm achieved IGA 0/1 plus at least a two-point improvement, as compared with 13% of placebo-treated patients (P<0.05). Treatment with a lower dose of the S1P₁ modulator led to a 12-week response rate of 14.9%.

Analysis of PROs showed significant (P<0.05) increases versus placebo in ≥4-point improvement in peak pruritus (42.1% vs 27.0%), ≥4-point improvement in a dermatology-specific quality of life (85.7% vs 64.1%), and ≥4-point improvement in Patient-Oriented Eczema Measure (73% vs 43.6%; 80.6% for etrasimod 1 mg, P<01).

No serious adverse events occurred during the trial, reported Emma Guttman, MD, of the Icahn School of Medicine at Mount Sinai in New York City.

"These results support the rationale of S1P₁ as a potential new mechanism of action and oral treatment for patients with atopic dermatitis," she said. "I think it suggests that it should be further investigated in a phase III trial."

S1P₁ modulation may interfere with molecular signaling involved in multiple aspects of AD pathogenesis: reduced activation of T cells in lymph nodes, reduced migration of lymphocytes from lymph nodes, and broad limitation of T-cell trafficking, including Th2 and Th1 tissue cytokines.

Guttman reported secondary findings from a phase II trial of etrasimod. Investigators in the multicenter trial randomized 140 patients with either of two doses of once-daily etrasimod or placebo, with outcome assessments at 12 weeks and an open-label extension with planned follow-up to 72 weeks.

The trial of percent change in EASI score, but IGA 0/1 is considered a valid endpoint for registration purposes. Guttman said the drug has entered phase III evaluation for moderate-severe ulcerative colitis and is being investigated as a potential therapy for alopecia areata, eosinophilic esophagitis, and Crohn's disease.

BTK Inhibitor Active in Pemphigus

An oral Bruton tyrosine kinase (BTK) inhibitor achieved disease control within 4 weeks in half of patients with moderate-severe pemphigus, a preliminary clinical trial showed.

Overall, 14 of 27 patients had disease control (i.e., no new lesions, existing lesions beginning to heal) after 4 weeks of treatment with rilzabrutinib. By week 12, an additional five patients had disease control. Six patients met the criteria for complete response by week 20, including four at week 12.

Disease control rates were similar in patients with newly diagnosed, relapsing/chronic, moderate, or moderate-severe pemphigus, reported Dedee Murrell, MD, of the University of New South Wales in Sydney, Australia.

"This study of rilzabrutinib, the first BTK inhibitor to be trialed in pemphigus, showed a rapid clinical effect, achieving disease control in 52% of patients in 4 weeks, improved disease severity, reduced corticosteroid use over a short time, and similar outcomes in both newly diagnosed and relapsing pemphigus," she concluded. "In terms of safety, we saw only transient and mild to moderate adverse events, giving an overall favorable risk/benefit profile and improved quality of life."

BTK has a in rapid innate and delayed adaptive immune responses in pemphigus. Murrell reported data from one component of a multipart phase II proof-of-concept trial of rilzabrutinib in patients with moderate (Pemphigus Disease Activity Index, PDAI 8-15) or moderate-severe (PDAI ≥15) newly diagnosed or relapsing pemphigus. In addition to daily oral rilzabrutinib, patients could also receive daily low-dose corticosteroids.

PDAI scores remained below baseline during follow-up to 24 weeks. Qualify-of-life scores increased within 4 weeks of the start of treatment and remained below baseline values to week 24.