Long-term tildrakizumab safe, effective in psoriatic patients with or without MetS

The efficacy and safety of long-term tildrakizumab are comparable and maintained without evidence of reduced durability of response through 148 weeks of treatment in patients with and without metabolic syndrome (MetS), results from two phase III trials have shown.

“[N]o difference in the incidence of cardiovascular (CV) events or worsening diabetes was observed—despite higher risk for CV events, diabetes, and obesity-related events—between patients with and without MetS across tildrakizumab doses,” the researchers said.

Posthoc analyses were carried out on 3 years of efficacy data and 5 years of safety data from the phase III, double-blind, randomized controlled reSURFACE 1 and 2 trial base and extension studies for patients receiving continuous tildrakizumab 100 or 200 mg.

Of the 338 (n=124 in reSURFACE 1 and n=214 reSURFACE 2) and 307 (n=147 in reSURFACE 1 and n=160 in reSURFACE 2) patients continuously receiving tildrakizumab 100 and 200 mg, respectively, 70 (21 percent and 21 percent) in the former dose and 64 (23 percent and 19 percent) in the latter met the MetS criteria. [J Am Acad Dermatol 2021;84:398-407]

At week 52, the proportions of patients achieving 75-percent improvement in the Psoriasis Area and Severity Index (PASI) in reSURFACE 1/2 were comparable among those with versus without MetS (tildrakizumab 100 mg: 85 percent and 86 percent vs 86 percent and 94 percent; tildrakizumab 200 mg: 76 percent and 87 percent vs 76 percent and 87 percent). These results persisted through week 148.

Responders with 90-percent and 100-percent improvement in the PASI also showed similar results. The safety of tildrakizumab did not vary by MetS status.

“The pathogenetic mechanisms underlying the relationship between obesity and psoriasis are not fully defined,” the researchers said. “Proposed mechanisms include shared underlying inflammatory pathways, including T helper 1 and 17 cells; dysregulation of adipocytokine secretion; and insulin resistance.” [J Dermatolog Treat 2008;19:5-21; J Rheumatol Suppl 2012;89:24-28; Nat Rev Immunol 2011;11:85-97; Dermatol Ther 2010;23:137-143; PLoS One 2017;12:e0181039]

In patients with moderate-to-severe psoriasis, short-term treatment (12–16 weeks) with tumour necrosis factor antagonists and interleukin (IL)-17 and IL-12/23 inhibitors was generally well tolerated, as shown in previous studies. [Br J Dermatol 2017;176:890-901; J Dermatolog Treat 2018;29:569-578; J Invest Dermatol 2016;136:1584-1591; J Invest Dermatol 2015;135:2641-2648]

However, some biologic therapies increased the risk for serious infections, such as lower respiratory tract and skin/soft tissue infections, following psoriasis treatment. [J Invest Dermatol 2015;135:2632-2640; Br J Dermatol 2019;180:329-337; J Invest Dermatol 2018;138:534-541]

In the present study, the incidence of serious infections was low and similar between patients with and without MetS. Moreover, malignancy rates were comparable to previous reports in patients with psoriasis and higher in those with versus without MetS. [Diabetes Care 2012;35:2402-2411; Br J Dermatol 2014;170:366-373]

“Understanding the long-term safety profile of biologic therapies, particularly with regard to CV disease, serious infections, and malignancies in patients predisposed to these conditions, will be important to decision making in psoriasis treatment,” the researchers said.

Of note, the current study was limited by its small sample size and posthoc design.