GENEVA — Tildrakizumab, an investigational interleukin (IL)-23p19 inhibitor, appears to be effective for the treatment of chronic plaque psoriasis, according to long-term extensions of two phase 3 trials: reSURFACE1 and reSURFACE2 (Lancet. 2017;390:276-288).
More than 80% of patients treated with tildrakizumab 200 mg for 2 years achieved a 75% reduction in Psoriasis Area Severity Index score (PASI 75), and adverse event rates were low.
“The as-observed analysis is sufficiently robust to say this is a good representation of the maintenance response we expect to see,” said investigator Kim Papp, MD, from Probity Medical Research in Waterloo, Canada. “And we see over 2 years only a gradual and minimal decline in PASI levels in both study populations.”
Tildrakizumab is likely to become the second IL-23 inhibitor to be approved by the US Food and Drug Administration (FDA), perhaps in the first quarter of 2018, said investigator Andrew Blauvelt, MD, from the Oregon Medical Research Center in Portland. Guselkumab (Tremfya, Janssen Biotech) was approved in July.
The advent of IL-23 inhibitors is an exciting advance in the treatment of psoriasis, Dr Blauvelt and other experts said here at the 26th European Academy of Dermatology and Venereology (EADV) Congress. These agents target psoriatic inflammation more precisely than biologics that aim to reduce all types of inflammation.
It’s important to clinical practice because agents that block more upstream in this pathway, such as IL-23, are dosed less frequently.
Because IL-23 expands a class of T-cells that produce the proinflammatory cytokine IL-17, it is considered a key driver in the development of psoriasis. Therefore, blocking IL-23 might be a more effective way to control psoriasis than targeting IL-17 alone.
“Agents that block IL-23 and IL-17 are more specific to psoriatic inflammation,” Dr Blauvelt told Medscape Medical News. “I like to describe IL-23 as more upstream in the immunologic cascade, and IL-17 as more downstream.”
“It’s important to clinical practice because agents that block more upstream in this pathway, such as IL-23, are dosed less frequently,” he explained. With agents that are more downstream, such as ixekizumab (Taltz, Lilly) and secukinumab (Cosentyx, Novartis), “dosing is more frequent and the disease returns more rapidly after discontinuation of the drug.”
In the reSURFACE1 open-label extension study, 506 of the 638 patients who completed the original study continued in the same treatment group — tildrakizumab 100 mg, tildrakizumab 200 mg, or placebo — and were evaluated at 64 weeks.
In the reSURFACE2 open-label extension study, 731 of the 756 patients who completed the original study continued in the same treatment group — tildrakizumab 100 mg, tildrakizumab 200 mg, etanercept (Enbrel, Amgen), or placebo — and were evaluated for 52 weeks.
All participants in the extension studies had achieved at least PASI 50 in the original studies. About two-thirds of the patients were male, and most were in their 40s, Dr Papp said.
Table. Response Rates in the Two Extension Studies
| Response | 100 mg Group, % | 200 mg Group, % |
|---|---|---|
| reSURFACE1 | ||
| PASI 50 | 98 | 97 |
| PASI 75 | 90 | 91 |
| PASI 90 | 74 | 82 |
| PASI 100 | 53 | 63 |
| reSURFACE2 | ||
| PASI 50 | 99 | 97 |
| PASI 75 | 92 | 88 |
| PASI 90 | 84 | 84 |
| PASI 100 | — | 70 |
| Physician Global Assessment | 66 | — |
Adverse events, including severe infections and malignancies, will be monitored for about 5 years, but rates were low for both doses at 2 years, and there were no deaths, Dr Papp reported.
“The long-term extension studies show that tildrakizumab is safe and effective over a 2-year period,” Dr Blauvelt said. “No surprises were seen in the second year of therapy, which is particularly good because we know that some of the earlier biologics tend to drop off in efficacy in the second year of therapy.”
It will be interesting to see whether tildrakizumab and other IL-23 inhibitors produce a better sustained response over many years than other agents, said Martin Röcken, MD, from the University of Tübingen in Baden-Württemberg, Germany, who is chair of the EADV scientific programming committee.
“It may also be an interesting drug to look at for safety data, because sometimes after giving an IL-17 agent, if you block it directly, you may see pustular effects,” Dr Röcken told by Medscape Medical News. “The big question regarding IL-23 is whether, if by acting indirectly on the IL-17 cells, you get better safety and more efficacy.”
This research is funded by Merck. Dr Papp is an investigator for Merck. Dr Blauvelt reports relationships with AbbVie, Amgen, Boehringer Ingelheim, Celgene, Dermira, Genentech, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Sandoz, Sanofi Genzyme, Sun Pharma, UCB, Valeant, Purdue Pharma, Sienna Pharmaceuticals, Almirall, Vidac, and Allergan. Dr Röcken reports financial relationships with AB Science, Abbott Laboratories, Abbott Pharmaceuticals, Almirall Hermal, AstraZeneca, Bayer, Biogen Idec, Bristol-Myers Squibb, Celgene, Galderma, GSK, Hokusai, Janssen-Cilag, Johnson & Johnson, Lilly, Merck, MSD Sharp & Dohme, Novartis, Pfizer, Philogen, Roche, Sanofi-Regeneron, Schering-Plough, and Sterna Biologicals.
26th European Academy of Dermatology and Venereology (EADV) Congress: Abstract D3T01.1H. Presented September 16, 2017.
Follow Medscape Dermatology on Twitter @MedscapeDerm and Maureen Salamon @maureensalamon
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