Poster abstracts 49
Dong 4, Yuhua Wang 4, Yanli Zhuang 4, William Barchuk 5, Xie L. Xu 5, Elizabeth Hsia 4
1
Division of Dermatology and Venereology, Geneva University Hospital, and Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland, 2 Department of Dermatology, New York Medical College at Metropolitan Hospital, New York, NY, 3 Oregon Health & Science University, Portland, OR, 4 Janssen Research & Development, LLC, Spring House, PA, 5 Janssen Research & Development, LLC, San Diego, CA, USA
Introduction / Objective: To evaluate the efficacy, safety & tolerability of guselkumab( GUS) in patients( pts) w / PsA. Methods: In this double-blind, PBO-controlled study, pts w / active PsA & ≥3 % BSA of PsO despite treatment were randomized 2:1 to SC GUS 100mg or PBO at wks0, 4, & q8w thereafter through wk44. At wk16, pts w / < 5 % improvement from baseline( BL) in swollen & tender joint counts were eligible for early escape( EE) to open-label ustekinumab. At wk24, PBO pts crossed-over to GUS 100mg( PBO to GUS). The primary endpoint was ACR 20 at wk24. Major secondary endpoints were PASI 75 & ACR 50 responses, change from BL in HAQ-DI, & improvement in enthesitis( Leeds enthesitis index [ LEI ]) & dactylitis score( by a 0 – 3 scoring system) at wk24; & ACR 20 response at wk16. Through wk24, efficacy analyses were performed in a modified Intent-to-Treat( mITT) population. Pts who met treatment failure criteria, EE or had missing data at wk24 were considered nonresponders for ACR / MDA endpoints at wk24. Efficacy post wk24 was evaluated in pts who did not EE & continued treatment at wk24 based on observed data. Results: Of 149 pts( PBO: 49, GUS: 100), BL demographics & ACR component measures were generally similar between the 2 groups. 4 PBO & 9 GUS pts were previously exposed to anti-TNFα agents. At wk24, significantly more GUS pts achieved ACR 20( 58.0 % vs 18.4 %, p < 0.001), PASI 75( 78.6 % vs 12.5 %, p < 0.001), & ACR 50( 34.0 % vs 10.2 %, p = 0.002) responses vs PBO. At wk24, mean decrease in HAQ-DI score from BL(-0.42 vs.-0.06, p < 0.001), & median percent improvement in enthesitis( 100 % vs 33.33 %, p = 0.009) & dactylitis( 100 % vs 33.33 %, p < 0.001) scores( among pts w / BL enthesitis and dactylitis) were significantly greater in GUS group vs. PBO. Significantly more GUS pts achieved ACR 20 at wk16( 60.0 % vs 16.3 %, p < 0.001) and MDA at wk24( 23.0 % vs. 2.0 %, p = 0.001) vs. PBO. Post wk24, efficacy improved in PBO to GUS crossover pts as expected and were well-maintained in GUS pts through wk56. Through wk24, the frequencies of AEs & infections were comparable( AEs: PBO 32.7 %; GUS 36.0 %; infections: PBO: 20.4 %; GUS: 16.0 %). Post wk24, there was no disproportional increase in AE frequency or infections among GUS pts w / longer exposure. Through wk56, there was 1 malignancy( basal cell carcinoma), 6 SAEs( myocardial infarction, osteoarthritis, pupils unequal, radius fracture, pneumonia, ulcerative keratitis), 2 pts discontinued treatment due to AEs, 1 grade 3 neutropenia, & 6 pts were positive for antibodies to GUS. No deaths occurred through wk56. Conclusions: GUS demonstrated significant improvement on joint symptoms, physical function, PsO, enthesitis, dactylitis & quality of life; efficacy was well-maintained through wk56. GUS was well tolerated in this population after ~ 1 year of exposure. Data has been previously presented at EULAR 2017 & ACR 2017
P120 TILDRAKIZUMAB EFFICACY OVER TIME BY WEEK 28 RESPONSE LEVELS IN TWO PHASE 3 CLINICAL TRIALS IN PATIENTS WITH CHRONIC PLAQUE
PSORIASIS Andrew Blauvelt 1, Howard Sofen 3, Kim Papp 3, Melinda Gooderham 4, Yang Zhao 5, Simon Lowry 5, Jeff Parno 5, Qing Li 6, Carmen La Rosa 6, Kristian Reich 7
1
Oregon Medical Research Center, Portland, OR, 2 Department of Medicine( Dermatology) UCLA, Los Angeles, CA, USA, 3 Probity Medical Research,
Waterloo, ON, 4 Skin Centre for Dermatology, Peterborough, ON, Canada,
5
Sun Pharmaceuticals, Princeton, NJ, 6 Merck & Co., Inc., Kenilworth, NJ, USA, 7 SCIderm Research Institute and Dermatologikum Hamburg, Hamburg, Germany
Introduction: Tildrakizumab( TIL), a humanized, IgG1 / κ monoclonal antibody for IL-23p19, recently demonstrated its efficacy in subjects with chronic plaque psoriasis in two, phase 3 clinical studies1. Objective: In this analysis, we examined efficacy from baseline to week 52 among TIL patients achieving various Psoriasis Area and Severity Index( PASI) responses at week 28. Methods: ReSURFACE 1( NCT01722331) and reSURFACE 2( NCT01729754) were double-blind, randomized controlled studies in subjects with moderate-to-severe chronic plaque psoriasis. Part 1( 0 – 12 weeks) was placebo controlled; Part 2( 12 – 28 weeks) re-randomized placebo patients to TIL; Part 3( 28 – 64 weeks, reSURFACE 1; 28 – 52 weeks, reSURFACE 2) re-randomized patients with ≥PASI 50 to continue or increase TIL dose or to placebo based on their PASI response at week 28. In this post-hoc pooled analysis, patients consistently on TIL 100 mg and 200 mg from baseline to week 52 were classified in 5 mutually exclusive groups based on their week-28 PASI response: PASI < 50, PASI 50 – 74, PASI 75 – 89, PASI 90 – 99, and PASI 100. Baseline characteristics and % PASI improvement from baseline up to week 52( observed data) were examined for each group. Results: This analysis included 575( TIL 100 mg) and 581( TIL 200 mg) patients; the proportions of patients with week-28 PASI 75 / 90 / 100 responses were 77 %/ 54 %/ 23 %( TIL 100 mg) and 78 %/ 58 %/ 29 %( TIL 200 mg). At week 28, 133( 23.1 %), 175( 30.4 %), 137( 23.8 %), 82( 14.3 %), and 48( 8.3 %) TIL 100 mg patients and 170( 29.3 %), 169( 29.1 %), 114( 19.6 %), 105( 18.1 %), and 23( 4.0 %) TIL 200mg achieved PASI 100, PASI 90 – 99, PASI 75 – 89, PASI 50 – 74, and PASI < 50, respectively. On average, PASI 100 patients were younger, lighter, and had shorter disease duration at baseline compared to other response groups. For TIL 100 mg, % PASI improvement was highest for PASI 100 and least for PASI < 50 patients on all visits up to week 28( week 4: 53 %, 46 %, 38 %, 30 %, and 16 %; week 28: 100 %, 95 %, 83 %, 64 %, and 33 % for PASI 100, PASI 90 – 99, PASI 75 – 89, PASI 50 – 74, and PASI < 50 categories, respectively). Among patients achieving PASI > 50 at week 28 and continued up to 52 weeks, % PASI improvement maintained or improved from week 28 to week 52. Similar results were observed for TIL 200 mg as well as a subgroup analysis with bio-naive and bio-experienced patients respectively. Conclusions: The majority of TIL 100 and 200 mg patients achieved PASI > 50 response at week 28, and PASI improvement was maintained from week 28 to week 52. Among patients achieving PASI > 90 at week 28, TIL 100 and 200 mg were associated with a rapid PASI improvement by week 4. Reference: 1. Reich K, Papp KA, Blauvelt A, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis( reSURFACE 1 and reSUR- FACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017; 390( 10091): 276-288. This abstract was presented at 2018 Annual Meeting of American Academy of Dermatology. Note: This abstract was presented at 2018 Annual Meeting of American Academy of Dermatology.
P122 POTENTIAL DISCONNECT: CO-MANAGEMENT OF PATIENTS WITH PSORIATIC ARTHRITIS BETWEEN
RHEUMATOLOGISTS AND DERMATOLOGISTS Lynn Price, Jennifer Robinson, Gianna Melendez Spherix Global Insights
Introduction: On average, the majority of psoriasis( PSO) patients are diagnosed a year prior to a psoriatic arthritis( PsA) diagnosis, making the referral patterns and co-management between derma-
Acta Derm Venereol 2018