Background Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis. Recent evidence with biologic medications that target IL-17 and IL-12/23 (i.e., secukinumab and ustekinumab) have demonstrated efficacy in the treatment of PsA leading to their inclusion in the 2015 EULAR recommendations for the management of psoriatic arthritis (1). Tildrakizumab is an investigational high-affinity, humanized, IgG1/κ, anti-IL-23p19 monoclonal antibody.
Objectives This analysis was done to evaluate the effect of tildrakizumab on PsA endpoints in a small population of patients with PsA participating in a Phase 2 chronic plaque psoriasis study.
Methods A randomized, double-blind study (NCT01225731) was conducted in 355 adults with moderate to severe plaque psoriasis. Patients were randomized to receive tildrakizumab 5 mg, 25 mg, 100 mg, 200 mg or placebo subcutaneously at Weeks 0 and 4, then every 12 weeks for 52 weeks. The primary efficacy endpoint was the proportion of patients achieving a PASI 75 at Week 16. Patients with PsA (defined by subject history) were examined. PsA endpoints included: mean change in Psoriatic Arthritis Screening and Evaluation (PASE), Health Assessment Questionnaire (HAQ), pain assessed with Visual Analog Scale (VAS), and high-sensitivity C-Reactive Protein (hsCRP), measured from baseline through Week 16.
Results 339 patients completed 16 weeks of treatment, PASI 75 responses were 33.3%, 64.4%, 66.3%, 74.4% and 4.4%, in the 5 mg, 25 mg, 100 mg, 200 mg tildrakizumab and placebo groups, respectively (p≤0.001) (2). Overall, 65 patients (18%) had PsA (5 mg n=8, 25 mg n=15, 100 mg n=17, 200 mg n=17, placebo n=26). Mean changes from baseline are listed below. Results show numerically greater improvements for all doses of tildrakizumab vs. placebo for PASE, and pain parameters. Additionally, tildrakizumab 25 mg and 200 mg demonstrated numerically greater improvement vs. placebo for HAQ (Table). In the overall study population, mean (SD) changes from baseline at Week 16 in observed hsCRP (mg/L) was -0.8 (5.7), -2.3 (6.1), -2.7 (9.2), -3.0 (13.4), and -1.3 (3.6) for the 5 mg, 25 mg, 100 mg, 200 mg, and placebo groups, respectively; hsCRP results for PsA patients only are shown (Table).
Conclusions Numerical improvements in measures of PsA were observed with tildrakizumab in a small sample of patients with chronic plaque psoriasis who had concomitant PsA. Tildrakizumab 25 mg, 100 mg, and 200 mg were associated with numerically lower hsCRP levels compared with 5 mg and placebo. Further research is needed to better evaluate tildrakizumab in the treatment of PsA.
Gossec L et al. Ann Rheum Dis 2015. doi: 10.1136/annrheumdis-2015-208337;
Papp K et al., Br J Dermatol 2015; 173: 887–888
Disclosure of Interest R. Langley Consultant for: AbbVie, Celgene, Centocor, Janssen-Cilag, LEO Pharma, Merck & Co., Inc., Novartis and Pfizer, D. Thaçi Consultant for: Abbott (AbbVie), Almiral, Amgen, Astellas, Biogen Idec, Boehringer Ingelheim, Celgene, Dignity, Forward Pharma, Galderma, GlaxoSmithKline, Isotechnika, Janssen-Cilag, LEO Pharma, Lilly, Maruho, Medac, Medimmune, MSD, Merck Serono, Novartis, Regeneron, Sandoz, Sanofi-Aventis, Takeda and Pfizer., K. Reich Consultant for: AbbVie, Amgen, Biogen Idec, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Lilly, Medac, Merck, Novartis, Pfizer, Vertex and Takeda., K. Papp Consultant for: Abbott (AbbVie), Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, Centocor, Foreward Pharma, Galderma, Genentech, Incyte, Isotechnika, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Medimmune, Merck Sharp Dome, Merck Serono, Novartis, Regeneron, Stiefel, Takeda, Pfizer and USB., A. Mehta Employee of: Merck & Co., Inc., Q. Li Employee of: Merck & Co., Inc., C. La Rosa Employee of: Merck & Co., Inc.