The objective of this study was to assess the effect

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1 Adalimumab is Associated with Reduced Skin Pain in Patients with Moderate to Severe Hidradenitis Suppurativa (HS): Results from the First 12 Weeks of PIONEER II Alexandra B Kimball 1, Brett Pinsky 2, Ziqian Geng 2, Martin Okun 2, Yanjun Bao 2, Murali Sundaram 2 1 Harvard Medical School, Boston, MA, United States; 2 AbbVie Inc., North Chicago, IL, United States Presented at the 73rd Annual Meeting of the American Academy of Dermatology, San Francisco, California, March 20 24, 2015 BACKGROUND Hidradenitis Suppurativa (HS)/Acne Inversa, is an inflammatory skin disease characterized by recurrent, painful abscesses and nodules that may lead to physical debilitation and psychological strain. 1,2 Pain has been identified as the most burdensome issue to patients with moderate to severe HS. 3 Currently there are no approved pharmaceutical treatments for HS. The current study, PIONEER II, is a randomized, placebo (PBO) controlled trial of adalimumab (ADA) treatment in patients with moderate to severe HS. OBJECTIVE The objective of this study was to assess the effect of ADA treatment compared with PBO on pain experienced in patients with moderate to severe HS.

2 METHODS Study Design Patients were randomly assigned (in a 1:1 ratio) to receive ADA 40 mg every week or PBO. ADA was administered as a subcutaneous injection, 160 mg at Week 0, 80 mg at Week 2, and 40 mg weekly starting from Week 4 (Figure 1). The results described in this poster encompasses Period A of PIONEER II. Figure 1. Study Design a Starting at Week 4 following 160 mg at Week 0, 80 mg at Week 2. This analysis encompasses Period A. Abbreviation: ADA, adalimumab.

3 METHODS (CONTINUED) Patients Eligibility for study participation included the following: adult men and women who were anti TNFα naïve, diagnosed with HS for 1 year prior to baseline, and had an inadequate response to a trial of oral antibiotics for the treatment of HS. Patients had a total abscess and inflammatory nodule (AN) count of 3. HS lesions were to be present in 2 body areas, one of which was Hurley Stage II or III. 4 Exclusion from study participation included prior treatment with anti TNFα; other active skin disease that could interfere with assessment of HS; and draining fistula count of >20 at baseline. Subjects requiring oral opiod analgesics were excluded from enrollment; permitted analgesic use for HS related pain included ibuprofen, acetaminophen, or tramadol (if ibuprofen or acetaminophen was insufficient). Concomitant use of oral antibiotic therapy (doxycycline or minocycline) for the treatment of HS is allowed provided the dosing regimen has been stable for at least 28 days prior to Baseline and the regimen must remain stable throughout study participation. Pain Assessment Daily patient reported Pain diary: In the last 24 hours, which number best describes your skin pain at its worst due to your HS. Daily assessments were evaluated and weekly average was used. 11 point Numeric Rating Scale (NRS) (0 10), where 0 = no pain and 10 = worst pain imaginable. Data Analyses Change from baseline pain and the proportion of patients who had at least 30% reduction in pain (NRS30) were examined at weeks 2, 4, 8, and 12. Patients with evidence of strong analgesic use (i.e., other than acetaminophen, ibuprofen, or tramadol) for HS related pain were considered to be nonresponders. All pain analyses were limited to patients with a baseline NRS score 3. Change in skin pain was calculated using analysis of covariance controlling for baseline Hurley stage, baseline pain value, and antibiotic use. Proportion of patients achieving an NRS30 was compared using a Cochran Mantel Haenszel test adjusting for baseline Hurley stage and antibiotic use.

4 RESULTS Study Population 326 patients were randomly assigned to ADA weekly or PBO in Period A (ITT_A population) (Figure 1). Of the 326 patients in the ITT_A Population, the majority were female (67.8%) and white (83.7%). The mean age of patients was 35.5 years. Patients had HS for an average of 11.5 years, and had a mean AN count of 11.3 (Table 1). At baseline, patients reported having moderate pain (ADA=5.7; PBO=6.2) among patients with NRS baseline score 3. Table 1. Patient Demographics and Baseline Characteristics (ITT_A Population) Total N=326 PBO (N=163) ADA Weekly (N=163) Female, n (%) 221 (67.8) 113 (69.3) 108 (66.3) Male, n (%) 105 (32.2) 50 (30.7) 55 (33.7) White, n (%) 273 (83.7) 130 (79.8) 143 (87.7) Black, n (%) 29 (8.9) 20 (12.3) 9 (5.5) P Value PBO vs ADA Weekly Age, years; mean [SD] 35.5 [11.13] 36.1 [12.18] 34.9 [9.96] Hurley Stage II a,n(%) 175 (53.7) 89 (54.6) 86 (52.8) Hurley Stage III a, n (%) 151 (46.3) 74 (45.4) 77 (47.2) Disease duration, years; mean [SD] 11.5 [9.03] 11.8 [9.41] 11.3 [8.66] AN count; mean [SD] 11.3 [9.68] 11.9 [11.02] 10.7 [8.10] Modified Sartorius Score; mean [SD] [84.32] [88.00] [80.03] Current smokers, n (%) 214 (65.8) 109 (67.3) 105 (64.4) 0.64 NRS skin pain at worst b ; mean [SD] NRS skin pain at worst among patients with a baseline NRS of 3 b ; mean [SD] 4.5 [2.69] (n=314) 6.0 [1.87] (n=216) 4.8 [2.73] (n=155) 6.2 [1.88] (n=111) 4.3 (2.62] (n=159) 5.7 [1.85] (n=105) Abbreviations: PBO, placebo; ADA, adalimumab; AN, abscess and inflammatory nodule; NRS, numeric rating scale for pain.

5 RESULTS (CONTINUED) Improvements in Skin Pain from Baseline By week 12, ADA treated patients reported significantly (P <0.001) greater improvement in their skin pain scores compared with PBO treated patients (Figure 2). At week 12, the patients in the adalimumab group had their pain reduced 2.3 points from their baseline value compared on a 0.7 point reduction in the placebo group (P <0.001). The pain response is rapid and sustained. Figure 2: Reduction in NRS Score from Baseline to Weeks 2, 4, 8, and 12* *Imputation method used was Last Observation Carried Forward (LOCF). P <.0001.

6 RESULTS (CONTINUED) In addition, at week 12, a significantly (P <0.001) greater proportion of patients in the ADA group achieved at least a 30% reduction in skin pain compared with the PBO group (Figure 3). Figure 3: Proportion of Patients Achieving NRS30 at Weeks 2, 4, 8, and 12 * *Imputation method used was NRI; among subjects whose baseline NRS at worst 3. P <0.001.

7 CONCLUSION ADA treated patients had significantly greater improvements in HS related skin pain compared with those treated with PBO. The skin pain benefits were rapid, sustained and clinically meaningful. ACKNOWLEDGMENTS Joann Hettasch, PhD, of Arbor Communications, Inc., provided medical writing and editing services in the development of this poster. Financial support for these services was provided by AbbVie. DEDICATION The authors would like to dedicate this poster to Parvez Mulani. REFERENCES 1. Alikhan A, et al. J Am Acad Dermatol. 2009;60: Esmann S, Jemec GBE. Acta Derm Venereol. 2011;91: Smith HS, et al. Clin J Pain. 2010;26: Hurley HJ. In: Roenigk RK, Roenigk HH Jr, eds. Dermatologic Surgery: Principles and Practice. 2nd ed. New York: Marcel Dekker. 1996: FUNDING AND DISCLOSURES Design, study conduct, and financial support for the study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. All authors contributed to the development of the publication and maintained control over the final content. A Kimball is a consultant and investigator for AbbVie, Amgen, and Janssen, and has received fellowship funding from Janssen. M Sundaram, B Pinsky, Z Geng, M Okun, Y Bao: Employees of AbbVie, and may own stock or stock options in AbbVie.