Poster abstracts 25 anti – interleukin-23p19 monoclonal antibody that demonstrated efficacy in phase 3 trials in moderate to severe chronic plaque psoriasis( reSURFACE 1 [ NCT01722331 ] and 2 [ NCT01729754 ]) [ 1 ]. Objective: Here we investigated the relationship between TIL serum concentration, and efficacy and safety outcomes, in re- SURFACE 1 and 2. Methods: Placebo or TIL 100 mg or 200 mg was administered at Weeks 0 and 4, then every 12 weeks. Endpoints included proportion of patients achieving 75 % Psoriasis Area and Severity Index( PASI 75) improvement from baseline( PASI 75 responders). Pooled efficacy data for each dose from reSURFACE 1 and 2 were grouped into quartiles based on average( mean) serum TIL concentration during Weeks 0 – 12( Cav12). Associations between median Cav12 for each quartile( Q) and TIL dose were analyzed for PASI 75 response at Week 12 and adverse events( AEs). Results: TIL steady-state concentrations were achieved by Week 16 and were proportional to the dose administered. Median Cav12( range) for TIL Q1 – Q4, respectively, were 4.4( 2.1 – 5.2), 5.7( 5.2 – 6.4), 7.0( 6.4 – 7.8), and 8.7( 7.8 – 16.1) µ g / mL for TIL 100 mg( n = 616) and 8.7( 4.2 – 10.4), 11.5( 10.4 – 12.5), 14.1( 12.5 – 15.5), and 17.3( 15.5 – 30.6) µ g / mL for TIL 200 mg( n = 622). PASI responses were similar for corresponding quartiles across doses, with no relationship between serum concentration and patient response for Q1 – Q3. Greater PASI 75 responses were associated with the highest Cav12( Q4), particularly for TIL 100 mg where PASI 75 response rates( 95 % confidence intervals [ CI ]) were 58.4 %( 54.6, 62.3), 62.3 %( 58.4, 66.1), 59.2 %( 55.3, 63.1), and 73.7 %( 70.1, 77.0) for Q1 – Q4, respectively. Corresponding PASI 75 rates( 95 % CIs) for patients receiving 200 mg were 52.9 %( 49.0, 56.8), 68.6 %( 64.9, 72.2), 64.5 %( 60.6, 68.1), and 74.8 %( 71.2, 78.0) over Q1 – Q4. There were no associations between AE rates and serum concentrations, and incidence rates of any AE, any infections, serious infections, upper respiratory tract infections, malignancies, non-melanoma skin cancer, confirmed extended major cardiovascular events, and drug-related hypersensitivity for TIL-treated patients were similar to, or less than, for placebotreated patients. Conclusions: No relationship was apparent between TIL dose or Cav12 and PASI response, although the greatest response was seen for the highest serum concentration. Importantly, there were no associations between serum concentration and AE incidence. Study sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; analyses funded by Sun Pharmaceutical Industries, Inc. Reference: 1. Reich K, et al. Lancet. 2017; 390:276 – 288.
P055 LONG-TERM SAFETY AND EFFICACY OF ADALIMUMAB FROM THE PHASE 3 RANDOMIZED, PLACEBO-CONTROLLED TRIAL IN PATIENTS WITH
NAIL AND SKIN PSORIASIS Jeff Crowley 1, Paolo Gisondi 2, Ziqian Geng 3, Ofelia Reyes Servin 3
1
Bakersfield Dermatology, Bakersfield, CA, USA, 2 University of Verona, Verona, Italy, 3 AbbVie Inc, North Chicago, IL, USA
Introduction: We evaluated long-term( up to 52 weeks) safety and efficacy of originator adalimumab every-other-week treatment( ADA eow) for fingernail psoriasis( Ps) in patients( pts) with moderate-to-severe Ps with substantial, clinically impactful, moderate-to-severe fingernail Ps. Methods: In 26-week Period A, pts were randomized 1:1 to 40 mg ADA after initial 80 mg dose, or matching placebo( pbo). Period B( open-label, 26 weeks) entry criteria: completion of Period A, or ≥25 % increase from baseline in affected body surface area( BSA) at week 16. At Period B entry( week 26), Period-A pbo pts received an initial blinded dose of 80 mg ADA; all received ADA eow from weeks 27 through 51. We analyzed all pts who received
ADA throughout the 52 weeks. Efficacy is reported using multiple imputation( MI) for missing data, and as observed results. Results: Of the 217 randomized pts, 203 received at ≥1 dose of ADA, 188 entered Period B, and 168 completed the trial. Of those receiving continuous ADA treatment through 52 weeks( n = 109), response rates( MI) for key efficacy outcomes at weeks 26 and 52, respectively, were as follows. ≥75 % improvement from baseline in modified Nail Ps Severity Index( mNAPSI 75): 47.4 % and 54.5 %. Physician’ s Global Assessment of fingernail Ps of 0( clear) or 1( minimal) with ≥2 grades improvement from baseline( PGA-F 0 / 1): 51.1 % and 55.6 %. Mean change( improvement) from baseline in nail Ps pain( numerical rating scale [ NRS ]): 3.6 and 3.8. Mean change( improvement) from baseline in Nail Ps Physical Functioning Severity score( NPPFS): 3.4 and 3.9. Mean change( improvement) from baseline in Dermatology Life Quality Index score( DLQI): 9.1 and 9.0( n = 94). As observed response rates at weeks 26 and 52 respectively, were as follows. mNAPSI 75: 47 / 88( 53.4 %) and 52 / 80( 65.0 %). PGA-F 0 / 1: 48 / 88( 54.5 %) and 49 / 80( 61.3 %). Mean change( improvement) from baseline in nail Ps pain( NRS): 3.8( n = 92) and 4.4( n = 80). Mean change( improvement) from baseline in NPPFS: 3.9( n = 92) and 4.4( n = 80). Mean change( improvement) from baseline in DLQI: 9.3( n = 69) and 9.7( n = 65). Adverse events( AEs) per 100 pt years( E / 100PYs; in 140.3 PYs) were: any event, 352( 250.9), serious AEs, 21( 15.0); and serious infections, 9( 6.4). AE’ s were similar to those observed in phase 3 clinical trials of ADA for Ps. Conclusion: ADA treatment of nail Ps across 52 weeks demonstrated short- and long-term efficacy. No new safety signals were identified in these pts receiving ≥1 dose of ADA.
P056 EIGHT-YEAR INTERIM RESULTS FROM THE ESPRIT 10-YEAR POSTMARKETING SURVEILLANCE REGISTRY OF ADALIMUMAB FOR MODERATE TO
SEVERE PSORIASIS Jashin J. Wu 1, William Abramovits 2, Francisco Kerdel 3, Dilek Arika 4, Dianlin Guo 4, Hartmut Kupper 5, Vera Kuehnl 5, Rakesh Singh 4, Alan Fleischer 4
1
Kaiser Permanente Los Angeles Medical Center, Los Angeles, 2 Division of Dermatology, Baylor University Medical Center, Dallas, 3 Florida Academic Dermatology Centers, Miami, 4 AbbVie Inc., North Chicago, USA,
5
AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany
Introduction: ESPRIT is a 10-year( y) international prospective observational registry evaluating the long-term safety and effectiveness of originator adalimumab( ADA) in adult patients( pts) with moderate to severe chronic plaque psoriasis. Objectives: To determine safety, effectiveness, and pt-reported outcomes( PROs) over an 8-y period from an interim analysis of data collected from the ESPRIT registry. Methods: ESPRIT enrolled pts who were continuing ADA treatment from a current prescription or previous study participation, or initiating ADA ≤ 4 weeks of entering the registry. The All-Treated pt population( All-Rx) received at least 1 ADA dose in this registry. Pts were evaluated at 3 and 6 months( mos) post-enrollment, and then every 6 mos for up to 10 ys. This interim analysis includes data collected from 26 Sep 2008 through 30 Nov 2016. Incidence rates( IR) for all treatment-emergent adverse events( All-TEAEs) in All-Rx pts are reported as events per 100 pt-ys( E / 100PY) of overall exposure to ADA. Physician’ s Global Assessment( PGA) and PROs( US only) were evaluated in as-observed population( pt numbers were small at 96 mos). Results: For the 6045 All-Rx pts enrolled and dosed in ESPRIT, median duration of overall exposure to ADA was 3.9 ys. Registry discontinuation rate in All-Rx pts was 39.4 %; with the most common reason being lost to follow up( 18.2 %). IR( E / 100PY) for All-TEAEs was: overall 22.0; serious AEs 4.5; malignancies
Acta Derm Venereol 2018