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Twenty-four-week interim analysis from a phase 3 open-label trial of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa.

ABSTRACT: Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent painful inflamed nodules/abscesses and draining fistulas that negatively impact quality of life. Adalimumab, a monoclonal antibody against tumor necrosis factor-?, has been approved in the EU, USA and Japan for the treatment of moderate to severe HS. This is an interim analysis of an ongoing phase 3, multicenter, open-label, single-arm study of the safety and efficacy of adalimumab weekly dosing in Japanese patients with moderate to severe HS. Fifteen patients received adalimumab 160 mg at week 0, 80 mg at week 2 and 40 mg every week thereafter starting at week 4. The fulfillment of Hidradenitis Suppurativa Clinical Response was assessed under adalimumab treatment; clinical response was assessed by skin pain, total abscess and inflammatory nodule count and modified Sartorius score; and quality of life and safety were assessed. At week 12, 86.7% of patients achieved clinical response, with improvements at week 12 across the primary and secondary end points generally sustained through week 24. Adalimumab weekly dosing was generally safe and well tolerated with no new safety findings through week 24. These results suggest that adalimumab is effective and well tolerated in Japanese patients with moderate to severe HS.

SUBMITTER: Morita A

PROVIDER: S-EPMC6771639 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Twenty-four-week interim analysis from a phase 3 open-label trial of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa.

Morita Akimichi A Takahashi Hidetoshi H Ozawa Kentaro K Imafuku Shinichi S Nakama Takekuni T Takahashi Kenzo K Matsuyama Takashi T Okubo Yukari Y Kitamura Susumu S Matsuda Naoto N Zhao Yiwei Y Yokoyama Masayuki M Hayashi Nobukazu N Terui Tadashi T

The Journal of dermatology 20190708 9

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent painful inflamed nodules/abscesses and draining fistulas that negatively impact quality of life. Adalimumab, a monoclonal antibody against tumor necrosis factor-α, has been approved in the EU, USA and Japan for the treatment of moderate to severe HS. This is an interim analysis of an ongoing phase 3, multicenter, open-label, single-arm study of the safety and efficacy of adalimumab weekly dosing in Japanese patien ...[more]

PMID: 31282051

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Project description:Hidradenitis suppurativa (HS) is a painful chronic skin disease characterized by abscesses, nodules, and tunnels in the skin. Adalimumab, a monoclonal antibody against tumor necrosis factor-α, is approved for the treatment of HS in Europe, the USA, and Japan. This multicenter, open-label, post-marketing, observational study (ClinicalTrials.gov: NCT03894956) evaluated the safety and effectiveness of adalimumab in routine clinical practice in Japan (March 2019-May 2021). Patients with HS were treated with s.c. doses of adalimumab according to the dosage described in the package insert. The primary end-point was safety (data cut-off, December 2020). Secondary end-points assessed effectiveness, including HS Clinical Response (HiSCR), skin pain, Dermatology Life Quality Index (DLQI), and C-reactive protein (CRP). Here, we report 12-week interim effectiveness results. A total of 84 eligible patients from 65 sites were enrolled; 83 patients were included in this analysis. Mean age was 42.0 years, mean body mass index was 26.9 kg/m2 , 78.3% of patients were male, 61.4% had Hurley stage III disease, 39.8% had a disease duration ≥10 years, and 7.2% had a family history of HS. The most common affected sites were the axilla (60.2%), buttocks (59.0%), and the inguinal and femoral regions (47.0%). Mean abscess and inflammatory nodule count was 13.0 (standard deviation, 12.0). Among patients with a comorbidity (57.8%), the most common were diabetes mellitus, hypertension, and chronic kidney disease. No patient reported a serious infection or any safety event of special interest. One patient died from a serious adverse event of cardiac failure unrelated to adalimumab. At week 12, 57.4% of patients achieved HiSCR, and significant reductions from baseline in skin pain, DLQI (both p < 0.0001), and CRP (p = 0.0029) were observed. These results support the administration of adalimumab as a well-tolerated and effective treatment for Japanese patients with HS in real-world clinical practice.

Project description:ImportanceSurgery is a mainstay in the management of hidradenitis suppurativa (HS). Adalimumab is the first drug approved for HS.ObjectiveTo investigate the efficacy and safety of adalimumab in combination with wide-excision surgery followed by secondary intention healing.Design, setting, and participantsThe Safety and Efficacy of Adalimumab for Hidradenitis Suppurativa Peri-Surgically (SHARPS) trial was a phase 4, randomized, double-blind, placebo-controlled study of adalimumab in conjunction with surgery. Patients were enrolled in 45 sites across 20 countries from July 18, 2016, to February 2, 2019, with the last patient visit on October 16, 2019. Eligible patients (aged 18-65 years) had moderate to severe HS that required radical surgery in an axillary or inguinal region and had 2 other anatomical regions affected, with 1 or more regions at Hurley stage II or III. Analysis was conducted in November 2019.InterventionsPatients were randomized 1:1 to receive continuous adalimumab, 40 mg, or placebo during presurgery (12 weeks), perioperative (2 weeks), and postoperative (10 weeks) periods.Main outcomes and measuresThe primary end point was the proportion of patients achieving HS clinical response across all body regions at week 12.ResultsOverall, 103 patients were randomized to adalimumab and 103 to matching placebo. Among all patients, 51% (n = 106) were women, 94% (n = 193) were White, and the mean (SD) age was 37.6 (11.3) years. At week 12, significantly more patients receiving adalimumab (49 of 103 [48%]) vs placebo (35 of 103 [34%]; P = .049) achieved HS clinical response across all body regions (treatment difference, 14% [95% CI, 0%-27%]). Treatment-emergent adverse events were reported in 74 of 103 patients (72%) and 69 of 103 patients (67%) in the adalimumab and placebo groups, respectively. No increased risk of postoperative wound infection, complication, or hemorrhage was observed with adalimumab vs placebo. Two deaths occurred in the adalimumab group; neither was considered as having a reasonable possibility of relationship to study drug.Conclusions and relevanceAdalimumab was efficacious in conjunction with wide-excision surgery followed by secondary intention healing, with no need to interrupt treatment prior to surgery. These data support further investigation of adalimumab as an adjuvant therapy to surgery in patients with moderate to severe HS.Trial registrationClinicalTrials.gov Identifier: NCT02808975.

Project description:BACKGROUND:Weekly adalimumab (Humira® ) is approved for the treatment of hidradenitis suppurativa (HS) based on the 12-week placebo-controlled periods of the two phase III PIONEER trials. OBJECTIVES:Using PIONEER integrated trial results, we aimed to evaluate the optimal medium-term adalimumab maintenance dosing strategy for moderate-to-severe HS. METHODS:Each trial had two double-blind periods; 12-week Period A and 24-week Period B. Patients randomized to adalimumab 40 mg every week (ADAew) (Period A), were rerandomized in Period B to ADAew (ADAew/ew), ADA every other week (ADAew/eow), or placebo (ADAew/pbo). Placebo-randomized patients were reassigned in Period B to ADAew (PIONEER I) or placebo (PIONEER II). The primary outcome was HS Clinical Response (HiSCR). Patients who lost response during Period B were discontinued from the study and offered an option to enter the open-label extension (OLE) to receive ADAew. Results are reported across the two study periods, and data were combined from the two study periods and the OLE. RESULTS:For week-12 HiSCR achievers, the HiSCR week-36 rate was 48·1% (ADAew/ew) vs. 46·2% (ADAew/eow) and 32·1% (ADAew/pbo). Combining (post hoc) these patients with week-12 partial responders further differentiated outcomes in Period B (ADAew/ew 55·7% vs. ADAew/eow 40·0% and ADAew/pbo 30·1%). Period-B adverse-event rates were ADAew/ew 59·6% vs. ADAew/eow 57·4% and ADAew/pbo 65·0%. One patient (ADAew/ew) reported a serious infection. CONCLUSIONS:Weekly adalimumab treatment, effective throughout 36 weeks, was the optimal maintenance medium-term dosing regimen for this population. At least partial response after 12 weeks with continued weekly dosing had better outcomes than dose reduction or interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy. No new safety risks were identified. What's already known about this topic? Hidradenitis suppurativa (HS) is a chronic inflammatory disease, commonly misinterpreted as an infection and treated with long-term antibiotic regimens or surgical incisions. Based on the chronicity of HS and the lack of evidence for efficacious and safe long-term HS treatments, it is important to evaluate medium- to long-term therapies for HS. Weekly adalimumab (Humira® ) is approved for the treatment of moderate-to-severe HS based on the two phase III PIONEER trials. What does this study add? This study pooled data from the two PIONEER trials, providing a more robust assessment of outcomes. After at least partial treatment success with weekly adalimumab short-term therapy (12 weeks), continuing weekly dosing during the subsequent 24 weeks had better outcomes than dose reduction or treatment interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy.

Dataset Information

Twenty-four-week interim analysis from a phase 3 open-label trial of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa.

Publications

Twenty-four-week interim analysis from a phase 3 open-label trial of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa.

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