Adalimumab in Japanese patients with active ulcers of pyoderma gangrenosum: Twenty‐six‐week phase 3 open‐label study

Abstract

This phase 3 multicenter study, including 26-week treatment and extension periods, evaluated the efficacy and safety of adalimumab in Japanese patients with active ulcers due to pyoderma gangrenosum. Patients received adalimumab 160 mg at week 0, 80 mg at week 2, and then 40 mg every week starting at week 4. Of the 22 enrolled patients, 12 (54.5%, P < 0.001) achieved the primary efficacy end-point of pyoderma gangrenosum area reduction 100 (PGAR 100, defined as complete skin re-epithelialization) for the target ulcer at week 26 assessed by digital planimetry. PGAR 100 response was observed as early as week 6 (13.6%) and continued to increase over time. The mean percent change from baseline in target ulcer area was À31.8% at week 6 and À63.8% at week 26. A Physician's Global Assessment score of 0 (PGA 0, all ulcers completely clear) was achieved by two patients (9.1%) at week 6 and eight (36.4%) at week 26, while PGA 0/1 (completely/almost clear) was achieved by five (22.7%) and 12 patients (54.5%) at week 6 and 26, respectively. Mean changes from baseline in pain numeric rating scale (À1.8 at week 6 and À2.5 at week 26) and the Dermatology Life Quality Index (À3.1 at week 6 and À3.6 at week 26) improved over time. Adverse events were reported by 18 patients, most commonly infections (n = 11), and serious adverse events by four. These results suggest that adalimumab is effective and generally well tolerated in Japanese patients with active ulcers of pyoderma gangrenosum.

Multifocal Pyoderma Gangrenosum with an Underlying Hemophagocytic Lymphohistiocytosis: Case Report and the Review of the Literature

“…Although the role of cytokines in pathogenesis of PG is not fully understood, overexpression of tumor necrosis factor alpha (TNFα) is associated with the neutrophil infiltration characteristic of PG; therefore, this group of drugs may be useful. A multicenter study evaluated the efficacy and safety of adalimumab in active ulcers of PG [ 46 ]. In this clinical trial, 22 enrolled patients received adalimumab 160 mg at week 0, followed by 80 mg at week 2, and then 40 mg every week starting at week 4.…”

Adalimumab in Japanese patients with active ulcers of pyoderma gangrenosum: Final analysis of a 52‐week phase 3 open‐label study

“…To address the need for alternative medication for refractory PG, we carried out a phase 3 randomized open‐label study to evaluate the efficacy, safety, and pharmacokinetics of adalimumab 40 mg every week for 52 weeks in Japanese patients with active ulcers of PG. Analysis at 26 weeks showed that the primary endpoint of PG area reduction 100 (PGAR 100, defined as complete skin re‐epithelialization) in the target ulcer was achieved by 12 of the 22 participants (54.5%) 16 . Findings from this interim analysis supported the approval of adalimumab (Humira®) for the treatment of PG in Japan in November 2020.…”

“…Eligibility criteria for the study have been reported previously 16 . In brief, patients ≥18 years old, diagnosed by the investigator as having active ulcerative (classic) PG (including peristomal PG), and who had an inadequate response to or were not candidates for topical PG therapy, were eligible for inclusion.…”

“…The primary efficacy endpoint of this study, the proportion of patients who achieved PG area reduction (PGAR) 100 (defined as complete skin re‐epithelialization) for the target ulcer at week 26 as assessed by photography‐based digital measurements (digital planimetry) (Table S3) as well as the key secondary endpoints at week 26, have been described previously 16 …”

Successful Treatment of Ulcerative-Type Pyoderma Gangrenosum with a Combination Therapy of Oral Prednisolone, Vacuum-Assisted Closure, and Skin Grafting

“…Moderate-dose systemic corticosteroid has long been used for the treatment of PG. However, because of several adverse effects [ 1 , 9 ], adalimumab was adopted as a treatment owing to its effectiveness and safety compared to oral corticosteroid with regard to the healing speed of intractable ulcer [ 10 , 11 ].…”