Tildrakizumab Effective for Patients with Psoriasis Unresponsive to Anti-IL17

Matteo Megna, MD

Credit: ResearchGate

Tildrakizumab can be an effective treatment option for patients with psoriasis who are unresponsive to anti-IL17, a study found.¹

“Our study was the first to specifically investigate the effectiveness of tildrakizumab after anti-IL17 failure, also with a focus on difficult-to-treat areas,” wrote investigators, led by Matteo Megna, MD, and Angelo Ruggiero, from the department of Clinical Medicine and Surgery at the University of Naples Federico II, in Italy.

Psoriasis affects 3% of the global population and can coexist with other conditions such as psoriatic arthritis (PsA), inflammatory bowel disorders, metabolic syndrome, type 2 diabetes, cardiovascular disorders, and psychiatric illness, making it crucial to treat this skin condition.^2,3 New knowledge on psoriasis pathogenesis, specifically the role of the interleukin (IL)23-Th17 axis, led to the development of new selective drugs—including Tildrakizumab.⁴

Tildrakizumab, a humanized IgG1/k-type monoclonal antibody targeting the p19 protein submit of IL23, has demonstrated effectiveness and safety in several clinical trials and real-life experiences.¹ However, the antibody’s efficacy and safety were unknown for patients with psoriasis who were unresponsive to anti-IL17 with brodalumab, ixekizumab, bimekizumab, and secukinumab.

Investigators conducted a 28-week, single-center, real-life, retrospective study aiming to assess the efficacy and safety of tildrakizumab in patients who previously failed anti-IL17. The team focused on examining psoriasis in difficult-to-treat areas, including the scalp, palms, soles, fingernails, and genitals.

“These data are important to understand if a previous failure of a drug acting on the IL23/17 axis may reduce the effectiveness of a second biologic active on the same pathway,” investigators wrote.

Leveraging participants with moderate-to-severe psoriasis from the Psoriasis Care Centre of Dermatology at the University Federico II of Naples, the study included 23 patients with 52.2% males (n = 12) and a mean age of 52.8 ± 12.4 years. The mean psoriasis duration was 13.8 ± 9.7; 3 participants also had psoriatic arthritis.

Participants were included if they were ≥ 18 years old, had moderate-to-severe plaque psoriasis assessed by a dermatologist for ≥ 6 months, tildrakizumab treatment for psoriasis for ≥ 16 weeks, and had a previous failure of ≥ 1 anti-IL17.

Patients were previously treated with a conventional and biological systemic treatment containing methotrexate. In total, 47.8% failed secukinumab (n = 11), 30.4% failed ixekizumab (n = 7), 13% failed brodalumab (n = 3), 4.3% failed both secukinumab and ixekizumab (n = 1), and 4.3% failed bimekizumab (n = 1).

Participants had a baseline PASI score of 12.8 ± 5.9 and a BSA score of 18.7 ± 9.6. After taking tildrakizumab, patients had statistically lower PASAI and BSA scores at week 16 (PASI: 4.8 ± 4.2; BSA: 7.2 ± 4.6, P <0.0001 for both) and week 28 (PASI: 2.1 ± 3.4; BSA: 3.7 ± 2.5, P <.0001 for both).

By week 16, 65.2% and 39.1% of patients achieved a PAS175 and PASI90 response, respectively. By week 28, the percentages increased with 82.6% and 56.6% of patients achieving a PAS175 and PASI90 response, respectively.

A sub-analysis revealed no differences existed in therapeutic outcomes for patients who failed different anti-IL17 (secukinumab or ixekizumab or brodalumab or bimekizumab).

Investigators found psoriasis in difficult-to-treat areas improved by week 16 and continued up to week 28, with a slower improvement in the palmoplantar area.

The team only observed 1 case of primary inefficacy and 1 case of secondary inefficacy. Additionally, they observed no severe adverse events.

Investigators outlined multiple limitations, including a small sample size, limited follow-up period, and using a retrospective study design.

“Tildrakizumab seems to be a valuable option in selected patients with psoriasis unresponsive to anti-IL17, suggesting that prior exposure to biological therapies seem not [to] directly affect its effectiveness,” investigators concluded.

References

1. ^{Megna M, Ruggiero A, Tommasino N, et al. Effectiveness and Safety of Tildrakizumab in Psoriasis Patients Who Failed Anti-IL17 Treatment: A 28-Week Real-Life Study. Clin Cosmet Investig Dermatol. 2024;17:1037-1042. Published 2024 May 7. doi:10.2147/CCID.S464326}
2. ^{Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386(9997):983–994. doi:10.1016/S0140-6736(14)61909-7}
3. ^{Yamazaki F. Psoriasis: comorbidities. J Dermatol. 2021;48(6):732–740. doi:10.1111/1346-8138.15840}
4. ^{Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci. 2019;20(6):1475. doi:10.3390/ijms20061475}