Adalimumab Efficacy in Hidradenitis Suppurativa Patients is Sustained at Least Three Years with Weekly Dosing: Results from a Phase 3 Open-Label Extension Study (PIONEER) Christos C Zouboulis,1 Martin M Okun,2 Robert Gniadecki,3 Peter A Foley,4 Charles Lynde,5 Jamie Weisman,6 Piyalal Karunaratne,7 David A Williams7 1Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Bradenburg Medical School Theodor Fontane, Dessau, Germany; 2Fort HealthCare, Fort Atkinson, WI, USA ; 3Bispebjerg Hospital, Copenhagen, Denmark; 4Department of Medicine (Dermatology), The University of Melbourne, St Vincent’s Hospital Melbourne, Skin & Cancer Foundation Inc, and Probity Medical Research, Carlton, Australia; 5The Lynde Centre for Dermatology and Probity Medical Research, Markham, ON, Canada; 6Advanced Medical Research, PC, Atlanta, GA, USA; 7AbbVie Inc, North Chicago, IL, USA INTRODUCTION 1. Kimball, NEJM. • Data (LOCF) for the HS patient populations receiving weekly ADA spanning the PIONEER I and II studies and the OLE, confirm that weekly ADA treatment maintained long-term response, demonstrated by: – 52.3% of the ADAew Population and 57.1% of the PRR Population achieved HiSCR at week 168 – Pain decreased starting at week 2, and was generally maintained to week 168 for both populations – Clinically meaningful improvement in DLQI at week 72 of 6.5 • The safety profile of long-term weekly ADA therapy in this analysis was consistent with the known ADA safety profile and no new safety risks were identified. DISCLOSURES C Zouboulis has received honoraria from AbbVie for participation on ad boards, as a consultant, investigator, and speaker; his department received grants from AbbVie and Novartis for his participation as an investigator. M Okun received compensation from AbbVie for consultation services and is a former AbbVie employee. He has served as a consultant for Gilead Sciences and Crescendo Biosciences. R Gniadecki has received honoraria from AbbVie, Janssen, Novartis, and Amgen for participation on advisory boards, as a investigator, and speaker; his department received grants from AbbVie, Janssen and Novartis for his participation as an investigator. P Foley has served as a consultant, investigator, speaker and/or advisor for and/or received travel grants from Galderma, LEO/ Peplin, Ascent, Clinuvel, Janssen-Cilag, Eli Lilly, Australian Ultraviolet Services, Roche, CSL, 3M/iNova/Valeant, GSK/Stiefel, Abbott/AbbVie, Biogen Idec, Merck Serono, Schering-Plough/MSD, Wyeth/Pfizer, Amgen, Novartis, Celgene, Aspen, Boehringer Ingelheim and BMS. C Lynde has received honoraria as a principal investigator, speaker, and consultant for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Merck, Novartis, and Regeneron. J Weisman received research grants for investigator services from AbbVie, Allergan, Amgen, Astra Zeneca, Boehringer Ingelheim, Braintree, Celgene, Eli Lilly, Glaxo Smith Klein, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Steifel, Tigercat; and received honoraria for service on advisory boards and speaker’s bureaus from AbbVie, Amgen, Celgene, Eli Lilly, and Janssen. P Karunaratne, D Williams receive a salary as AbbVie employees, and may also receive stocks and/or stock options. AbbVie Inc. funded this study and participated in the study design; study research; collection, analysis and interpretation of data; and writing, reviewing and approving of this publication. All authors had access to the data, and participated in the development, review, and approval, and in the decision to submit this publication. The authors would like to acknowledge Yihua Gu for statistical support, and Jody Bennett for medical writing support in the production of this publication; both are employed by AbbVie. METHODS RESULTS CONCLUSIONS REFERENCES • Hidradenitis suppurativa (HS) is a painful, chronic skin disease, characterized by recurrent inflamed nodules and abscesses, fistula formation, purulent drainage, and subsequent scarring. • The PIONEER I and II phase 3 trials1 evaluated treatment of patients with moderate-to-severe HS, with originator adalimumab (AbbVie) dosed every week. Adalimumab (ADA) is approved for a wide range of inflammatory diseases, including moderate-to-severe HS. • The PIONEER trials were followed by a phase 3, open-label extension (OLE) trial (NCT01635764) designed to determine the long-term safety and efficacy of ADA in patients with moderate to severe HS. • This analysis reports long-term results for patients who received weekly ADA weekly throughout PIONEER I and II, and continuing through the OLE to week 168. • Patients in this analysis entered the OLE if they completed Periods A and B or lost response during Period B of PIONEER I or II. • In PIONEER I or II, patients were randomized to 40 mg weekly ADA at the start of the 12-week Period A, and upon completion of Period A, were re-randomized to 40 mg weekly ADA at the start of the 24-week Period B (Figure 1). Throughout the OLE, all patients received 40 mg weekly ADA. Figure 1. Study Design for PIONEER I and II, and Open-Label Extension a. Stratified by BL Hurley Stage II vs III (PIONEER I & II) & BL concomitant antibiotic use (PIONEER II). b. 160 mg week 0; 80 mg week 2; 40 mg from week 4. c. Re-randomization at entry to Period B, stratified by week 12 HiSCR status & BL Hurley Stage II vs III. d. 160 mg week 12; 80 mg week 14; 40 mg from week 16. ADA=adalimumab; ew=every week dosing; PBO=placebo; BL=baseline; PRO=patient-reported outcomes. STATISTICAL ANALYSIS • ADAew Population: patients who received continuous 40 mg weekly ADA in Periods A and B of PIONEER I or II and in the OLE. • PRR Population: patients in the ADAew Population who either achieved HiSCR at week 12, or did not achieve HiSCR but achieved at least a partial response to treatment at week 12 – HiSCR (Hidradenitis Suppurativa Clinical Response) was defined as ≥50% reduction in AN count with no increase in abscess count and no increase in draining fistula count relative to baseline – Partial response was defined as ≥25% reduction in total abscess and inflammatory nodule (AN) count relative to baseline, at the end of Period A in PIONEER I or II. • All patients who were treated with ADA weekly in Periods A and B of PIONEER I and II, and entered the OLE, were included in the analysis. • Missing values were handled by non-responder imputation (NRI) in Periods A and B of PIONEER I and II, and last-observation-carried-forward (LOCF) and observed case were used for both continuous and categorical variables. • Results are reported as “study weeks,” which consist of PIONEER + OLE weeks, shown consecutively. a. Weeks include PIONEER I or II + the OLE, listed consecutively. • The AN count, draining fistula count, and total fistula count (sum of draining fistulas and non-draining fistulas) (LOCF) decreased from baseline in both populations, and remained generally stable to study-week 168 (Figure 3A-C). Figure 3. Improvement in Lesion Count A. AN Count B. Draining Fistulas C. Total Fistulas a. Weeks include PIONEER I or II + the OLE, listed consecutively. Mean improvement is relative to baseline. • Improvement from baseline in pain (LOCF), indicated by mean percent decrease in NRS scores, remained generally stable in both populations to week 168 (Figure 4). Figure 4. Improvement in Skin Pain a. Weeks include PIONEER I or II + the OLE, listed consecutively. Mean changes are relative to baseline. Change in numeric rating scale (NRS) at worst at each visit among patients with baseline NRS ≥3. • In both populations, there was a clinically meaningful decrease in DLQI (LOCF) from baseline through week 72. (Figure 5A). The percentage of patients who achieved DLQI 0 or 1 increased from baseline to week 48 and was generally maintained to week 72 (Figure 5B). Figure 5. Improvement in Dermatology Specific Quality of Life A. Mean improvement from baseline B. Achievement of DLQI 0 or 1 a. Weeks include PIONEER I or II + the OLE, listed consecutively. Mean changes are relative to baseline. DLQI 0 or 1=Dermatology Quality of Life Index, no effect of skin disease on quality of life. SAFETY • There were no adverse events of opportunistic infection excluding oral candidiasis, no events of tuberculosis, lymphoma, non-melanoma skin cancer, malignancy, or demyelinating disorder, and there were no deaths. Table 2. Treatment-Emergent Adverse Events Adverse Events, n (%) ADAew Population N=88 PRR Population N=63 Any event 76 (86.4) 55 (87.3) Leading to study drug discontinuation 13 (14.8) 10 (15.9) Serious 12 (13.6) 9 (14.3) Infections 63 (71.6) 45 (71.4) Serious infections 3 (3.4) a 2 (3.2) b Active or latent tuberculosis 2 (3.2) 2 (3.2) a. Included pneumonia (n=2) and cellulitis of right leg (n=1). b. Included pneumonia (n=1) and cellulitis of right leg (n=1). • For patients who were randomized to weekly ADA in Period A of the 2 trials, the primary endpoint outcome (pooled data), was achievement of HiSCR at week 12 by 50.6% of patients (160/316), which was significantly higher than for patients randomized to placebo (26.8%; 85/317); P<0.001. • In this analysis of results across PIONEER I and II (pooled data) into the OLE, 88 patients were in the ADAew Population and 63 were in the PRR Population. • The HiSCR rate (LOCF) increased from baseline to week 48 in both populations and was maintained to week 108 (Figure 2). Figure 2. Achievement of HiSCR FC17PosterAbbVieZouboulisAdalimumabEfficacyinHidradenitis.pdf