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5 th World Psoriasis & Psoriatic Arthritis Conference 2018
were more likely to discontinue therapy than men. Males were more likely to remain on the first biologic therapy. Adalimumab and ustekinumab had lowest rates of discontinuation. Etanercept, infliximab and apremilast had the highest. References: 1. M. Esposito, et al. Survival rate of antitumour necrosis factor α treatments for psoriasis in routine dermatological practice: a multicentre observational study. Br J Dermatol( 2013). [ Online ] http:// onlinelibrary. wiley. com / doi / 10.1111 / bjd. 12422 / full. 2. R. Gniadecki et al. Comparison of long-term drug survival and safety of biologic agents in patients with psoriasis vulgaris. Br J Dermatology( 2014). [ Online ] http:// onlinelibrary. wiley. com / doi / 10.1111 / bjd. 13343 / full 3. A. A. Levin, A. B. Gottlieb, S. C. Au. A comparison of drug failure rates and reasons for discontinuation in biologics versus systemic therapies. Journal of Drugs in Dermatology( 2014) [ Online ] http:// europepmc. org / abstract / med / 25007369 4. R. B. Warren, et al. Differential Drug Survival of Biologic therapies for the treatment of psoriasis a prospective Observational cohort Study from the British association of Dermatologists Biologic interventions register( BADBIR). J Invest Dermatol( 2015). [ Online ] http:// www. sciencedirect. com / science / article / pii / S0022202X15418494 5. J. Zweegers, et al. Body mass index predicts discontinuation due to ineffectiveness and female sex predicts discontinuation due to side-effects in patients with psoriasis treated with adalimumab, etanercept or ustekinumab in daily practice: a prospective, comparative, long-term drug-survival study from the BioCAPTURE registry. Br J Dermatol( 2016) 175: 340 – 347. doi: 10.1111 / bjd. 14552.
P061 INCIDENCE OF INFECTIONS IN CLINICAL TRIALS OF TILDRAKIZUMAB FOR MODERATE TO SEVERE
PLAQUE PSORIASIS Jeffrey Crowley 1, Craig Leonardi 2, Sheila Sturgill-Koszycki 3, Alan Menter 4, Alan Mendelsohn 3, Qing Li 4, Nicole Cichanowitz 5, Carmen La Rosa 5
1
Bakersfield Dermatology, Bakersfield, CA, 2 Central Dermatology, St Louis, MO, 3 Sun Pharmaceutical Industries, Inc., Princeton, NJ, 4 Division of Dermatology, Baylor Scott & White and Texas A & M College of Medicine, Dallas, TX, 5 Merck & Co., Inc., Kenilworth, NJ, USA
Introduction: Risk of infections is a concern with cytokine inhibitor treatments. Objectives: This analysis assessed infections during phase 2 and 3 trials of tildrakizumab( TIL), a high-affinity, humanized, IgG1κ monoclonal antibody against IL-23p19 under development for moderate to severe chronic plaque psoriasis. Methods: Patients( Pts) were randomized in P05495( phase 2; NCT01225731), reSURFACE 1( phase 3; NCT01722331), and reSURFACE 2( phase 3; NCT01729754) [ 1,2 ]. In Part 1( Week([ W ] 1 – 16) of P05495, pts received subcutaneous( SC) TIL 5, 25, 100, or 200 mg or placebo( PBO) at W0 and W4 and were rerandomized to various TIL doses in Part 2( W16 – 52). In Part 1( W1 – 12) of reSURFACE 1 and 2, pts received SC TIL 200 mg, TIL 100 mg, or PBO at W0 and W4. Pts were rerandomized in Part 2( W12 – 28) and Part 3( W28 – 64 or W28 – 52 in reSURFACE 1 and 2, respectively). Etanercept( ETN) 50 mg was an active control in Parts 1 – 2 of reSURFACE 2. Treatment-emergent adverse event data pools( n = 2081) for the PBO-controlled and full trial periods( 52 weeks for P05495 / reSURFACE 2; 64 weeks for reSURFACE 1) were analyzed. Severe infections met the regulatory definition of a serious adverse event or required intravenous antibiotics. Results: In the PBO-controlled period, incidences of infections were comparable for TIL 100 mg and 200 mg( 23 % and 22 %, respectively) and PBO( 23 %); all were comparable with ETN( 24 %). Incidences of severe infections were low for all treatment groups( range, 0.0 %-0.3 %; TIL P≥0.6 vs PBO). In the full trial period, exposure-adjusted rates( pts / 100 pt-years) for infections with TIL 100 mg and 200 mg( 48.9 and 52.6, respectively) were lower than with PBO and ETN( 79.5 and 86.0, respectively). Exposureadjusted rates for severe infections were 1.10, 1.61, 1.96, and 0.91 for TIL 100 mg, TIL 200 mg, ETN, and PBO, respectively. In all, 33 severe infections were identified( respiratory: TIL 100 mg, 4 events; TIL 200 mg, 2 events; ETN and PBO, 0 events; skin: TIL 100 mg, 3 events; TIL 200 mg, 6 events; ETN, 2 events; PBO, 3 events; gastrointestinal: TIL 100 mg, 4 events; TIL 200 mg, 5 events; ETN and PBO, 0 events; urinary tract: TIL 200 mg, 1 event; ETN, 1 event; TIL 100 mg and PBO, 0 events). One pt had bone tuberculosis( TIL 200 mg; original purified protein derivative test was negative); 1 sepsis event( TIL 200 mg) occurred months after ending TIL treatment. Conclusion: Infection rates with TIL treatment were low and comparable to PBO and ETN during the PBO-controlled period. By W52 / 64, exposure-adjusted rates remained low for all groups. Reference: 1. Papp K, et al. Br J Dermatol. 2015; 173:930-939. 2. Reich K, et al. Lancet. 2017; 390:276-288. Acknowledgements: The studies were funded by Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Analyses were presented at the American Academy of Dermatology Annual Meeting, February 16-20, 2018, San Diego, CA, USA.
P062 EFFICACY AND SAFETY OF RISANKIZUMAB: RESULTS FROM TWO DOUBLE-BLIND, PLACEBO- AND USTEKINUMAB-CONTROLLED, PHASE 3 TRIALS IN
MODERATE-TO-SEVERE PLAQUE PSORIASIS Kenneth B. Gordon 1, Bruce Strober 2, Mark Lebwohl 3, Matthias Augustin 4, Andrew Blauvelt 5, Yves Poulin 6, Kim A. Papp 7, Howard Sofen 8, Lluis Puig 9, Peter Foley 10, Mamitaro Ohtsuki 11, Mary Flack 12, Ziqian Geng 13, Yihua Gu 13, Joaquin M. Valdes 13, Elizabeth H. Z. Thompson 14, Hervé Bachelez 15
1
Medical College of Wisconsin, Milwaukee, Wisconsin, 2 University of Connecticut Health Center and Probity Medical Research, Farmington, CT,
3
Icahn School of Medicine at Mount Sinai, New York, NY, USA, 4 University Medical Center Hamburg-Eppendorf( UKE), Hamburg, Germany, 5 Oregon Medical Research Center, Portland, OR, USA, 6 Centre Dermatologique du Québec Métropolitain, Québec, QC, Canada, 7 K Papp Clinical Research and Probity Medical Research, Waterloo, ON, Canada, 8 University of California, Los Angeles, School of Medicine, Los Angeles, CA, USA, 9 Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain, 10 The University of Melbourne, Parkville, Skin & Cancer Foundation Inc, Carlton, and Probity Medical Research, Carlton, VIC, Australia, 11 Jichi Medical University, Shimotsuke, Japan, 12 Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 13 AbbVie Inc., North Chicago, IL, USA, 14 AbbVie Inc., Redwood City, CA, USA, 15 Saint-Louis Hospital, Sorbonne Paris Cité University Paris Diderot, Paris, France
Introduction: Interleukin-23 is a key cytokine in the development and maintenance of psoriatic lesions. Risankizumab is a humanized IgG1 monoclonal antibody that binds to IL-23’ s p19 subunit, selectively inhibiting this critical cytokine and its role in psoriatic inflammation. Methods: UltIMMa-1( n = 506) and UltIMMa-2( n = 491) were replicate, randomized, double-blind, placebo- and active comparator-controlled studies that evaluated efficacy and safety of risankizumab in adult patients with moderate-to-severe plaque psoriasis. Patients were stratified by weight and prior TNFi-exposure and randomized 3:1:1 to receive 150 mg risankizumab, 45 / 90 mg ustekinumab( weight-based per label) or matching placebo. Patients were dosed at weeks 0, 4, 16, 28, and 40, with placebo crossover to risankizumab at week 16. Co-primary endpoints were PASI 90 and sPGA0 / 1 at week 16 versus placebo with comparisons between risankizumab and ustekinumab as ranked secondary endpoints. Missing data were imputed as non-response. Results: All primary and ranked secondary endpoints were met for both trials( p < 0.001). At week 16 of UltIMMa-1 & 2 trials, risankizumab-treated patients achieved significantly higher PASI 90( 75.3 %/ 74.8 %) and sPGA0 / 1( 87.8 %/ 83.7 %) response rates versus placebo-( 4.9 %/ 2.0 %; 7.8 %/ 5.1 %) or ustekinumab-treated www. medicaljournals. se / acta