By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a second interleukin-23 (IL-23) inhibitor for the treatment of adults with moderate-to-severe plaque psoriasis who are eligible for systemic therapy or phototherapy. Tildrakizumab-asmn is a humanized IgG1/k antibody that binds to the p19 subunit of IL-23, similar to guselkumab, a human IgG1/k antibody. Tildrakizumab-asmn is marketed as Ilumya.
Tildrakizumab-asmn is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.1
The recommended dose is 100 mg given subcutaneously at weeks 0, 4, and every 12 weeks thereafter.1 Ilumya is available as 100 mg/mL single-dose prefilled syringes.
The mean elimination half-life of tildrakizumab-asmn is approximately 23 days, which allows dosing every 12 weeks.
In contrast, guselkumab has a mean half-life of 15-18 days and is dosed every eight weeks.
The most frequently reported adverse reactions were infections (14%), injection site reactions (3%), and diarrhea (2%).1 Corresponding placebo rates were 12%, 2%, and 1%, respectively. Approximately 2.5% of subjects developed neutralizing antibodies. Cases of angioedema and urticaria have been reported.
The pathogenesis of psoriasis involves numerous proinflammatory cytokines, including tumor necrosis factor alpha and interleukins 12 (IL-12), 17A (IL-17A), and IL-23. Tildrakizumab-asmn binds to IL-23 and inhibits its interaction with the IL-23 receptor, thereby inhibiting the release of proinflammatory cytokines and chemokines.1 The efficacy and safety of tildrakizumab-asmn 100 mg compared to placebo were evaluated in two randomized, double-blind, placebo-controlled, 12-week trials.1,2 Subjects registered a Physician Global Assessment (PGA) score of ≥ 3 on a 5-point scale, Psoriasis Area Severity Index (PASI) score ≥ 12, and a minimum body surface area (BSA) involvement of 10%. At baseline, subjects demonstrated a median PASI of 17.8 and a BSA of 27%. Thirty-three percent of subjects scored 4 or 5 on the PGA scale. A total of 309 subjects were randomized to tildrakizumab-asmn in study 1 (reSURFACE 1) and 307 in study 2 (reSURFACE 2). Correspondingly, 154 and 156 were randomized to placebo, respectively. The co-primary endpoints were the proportion of subjects who achieved at least a 75% reduction in PASI (PASI 75) and the proportion of subjects with PGA scores of 0 or 1 and at least a two-point improvement.
PASI 75 results at 12 weeks were 64% vs. 6% in study 1 and 61% vs. 6% in study 2. PGA of 0 or 1 were 58% in study 1 and 55% in study 2 vs. 7% and 4% for placebo, respectively. In an active arm of study 1, a PGA score of 0 or 1 of 48% was achieved for etanercept.2 In study 1, 74% were responders at week 28. These responders were further randomized to continue tildrakizumab-asmn or placebo to week 64, at which time 84% maintained PASI 75 compared to 22% for placebo.1
Psoriasis is a chronic inflammatory autoimmune disease primarily affecting the skin. In some patients, joints are involved (psoriatic arthritis). Generally, topical therapy is effective for mild-to-moderate disease. For moderate-to-severe disease, treatment options include phototherapy, conventional systemic agents (e.g., methotrexate, acitretin), and biologics. Numerous biologics targeting the various proinflammatory cytokines are available. Tildrakizumab-asmn is the second drug (after guselkumab) that solely targets IL-23, while ustekinumab targets both IL-12 and IL-23. There are no direct comparisons between tildrakizumab-asmn and guselkumab; however, a systematic review and meta-analysis suggested similar efficacy.3 In an indirect comparison of the two IL-23 inhibitors in their clinical trials, a higher proportion of subjects on guselkumab achieved PASI 75 and a PGA score of 0 or 1 compared to tildrakizumab-asmn, suggesting greater efficacy.4 A similar analysis found ixekizumab (IL-17 inhibitor) as the most effective biologic, followed by secukinumab, brodalumab, and guselkumab.5 Tildrakizumab-asmn is a new biologic for the treatment of psoriasis but may not offer any clear therapeutic advantage over existing agents. The cost for tildrakizumab-asmn was not available at the time of this review.
- Ilumya Prescribing Information. Merck & Co., Inc., March 2018.
- Reich K, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): Results from two randomised controlled, phase 3 trials. Lancet 2017;390:276-288.
- Bilal J, et al. A systematic review and meta-analysis of the efficacy and safety of the interleukin (IL)-12/23 and IL-17 inhibitors ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab for the treatment of moderate to severe plaque psoriasis. J Dermatolog Treat 2018:1-37.
- Amin M, et al. Review of phase III trial data on IL-23 inhibitors tildrakizumab and guselkumab for psoriasis. J Eur Acad Dermatol Venereol 2017;31:1627-1632.
- Sbidian E, et al. Systemic pharmacological treatments for chronic plaque psoriasis: A network meta-analysis. Cochrane Database Syst Rev 2017;12:CD011535. doi: 10.1002/14651858.CD011535.pub2.