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

In this 52-week, phase 3 open-label study, efficacy and safety of adalimumab were evaluated in Japanese patients with active ulcers due to pyoderma gangrenosum (PG) during a 26-week treatment period and another 26-week extension period. Patients received adalimumab 160 mg at week 0, 80 mg at week 2, and 40 mg every week from week 4. At week 26, 12 of 22 patients (54.5%, p < 0.001) achieved the primary efficacy endpoint of PG area reduction 100 (PGAR 100, complete skin re-epithelialization) for the target ulcer. Nine patients with Physician's Global Assessment (PGA) score of 1, 2, or 3, including four patients achieving PGAR 100, continued into the extension period. During the extension period, six of nine patients (66.7%) achieved PGAR 100 for the target PG ulcer at 52 weeks; one patient who achieved PGAR 100 before week 26 experienced a relapse 162 days after achieving this endpoint. Six patients achieved PGA 0 by week 52, and one patient reported new ulcers at day 57 of the extension period. Continued improvements from study baseline to week 52 were observed in pain (mean [95% CI] -4.0 [-6.5 to -1.5] numeric rating scale) and Dermatology Life Quality Index (-7.3 [-15.1 to 0.4]). In addition to the adverse events (AE) reported in 18 patients (including four serious AE) through week 26 (most commonly infections [n = 11]), there was one 1 additional AE (infection) during the extension period. These results suggest that adalimumab is effective and generally well tolerated in Japanese patients with active PG ulcers.

Long-term analysis of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa: Open-label phase 3 results.

This phase 3, multicenter, open-label single-arm study evaluated adalimumab (ADA) in Japanese patients with moderate to severe hidradenitis suppurativa (HS). Fifteen patients received ADA 160 mg s.c. at week 0, 80 mg at week 2 and 40 mg at week 4 and every week thereafter. At any time after week 52, patients were given the option to receive 80 mg ADA every other week or remain on 40 mg every week. The primary end-point (achievement of HS Clinical Response [HiSCR] at week 24) and results up to week 24 were published previously. Secondary end-points included total abscess and inflammatory nodule (AN) count, 30% or more and 1 unit or more reduction in Patient's Global Assessment of Skin Pain Numeric Rating Scale (NRS30), modified Sartorius score and quality of life (QoL). After 12 weeks of ADA treatment, the achievement rate in HiSCR was 86.7%; HiSCR achievement rate was sustained through week 52 at 66.7%. Improvements at week 12 were also seen in the proportion of patients achieving an AN count of 0-2; NRS30 response rate among the nine patients with a baseline NRS of 3 or more; mean decrease in modified Sartorius score (61.4); and QoL as assessed by Dermatology Life Quality Index and Treatment Satisfaction Questionnaire; these improvements were maintained through 52 weeks. Similar efficacy was observed when patients switched dosing from ADA 40 mg every week to ADA 80 mg every other week. There were no new safety findings with ADA 40 mg weekly dosing during the study, and no differences in safety were found between patients who switched to 80 mg ADA every other week and patients who remained on 40 mg every week. The results of this study indicate that long-term ADA treatment is effective and well tolerated in Japanese patients with moderate to severe HS.

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

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 -31.8% at week 6 and -63.8% 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 (-1.8 at week 6 and -2.5 at week 26) and the Dermatology Life Quality Index (-3.1 at week 6 and -3.6 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.