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ORLANDO -- More than 80% of patients with moderate-severe plaque psoriasis attained 75% clearance with the anti-IL23p19 antibody tildrakizumab after inadequate response to etanercept (Enbrel), an analysis of two randomized trials showed.

Among 120 patients who switched from etanercept after 28 weeks of treatment, 81.4% met criteria for a PASI 75 response at 52 weeks. Almost 70% of the patients attained a Physician Global Assessment (PGA) 0/1 response (clear or nearly clear) after the switch.

"My interpretation of these results is that if you are not responding to etanercept, and you are being switched to tildrakizumab, the drug will work," , of SCIderm Research Institute and Dermatologikum Hamburg in Germany, said here at the American Academy of Dermatology (AAD) annual meeting. "If you are a nonresponder to etanercept, your chance of responding to this drug is pretty similar compared to patients who have not received etanercept at all."

"What does this mean for clinical practice?" Reich continued. "I think it means that the p19 inhibitors, as a class, will broaden our therapeutic armamentarium and give us the opportunity to induce response in patients who have not responded to the biologics we've had before."

Another report at AAD showed that about 90% of patients who achieved PASI 75 responses at 28 weeks maintained the responses at 64 weeks, and more than 80% of patients who relapsed after discontinuing treatment regained PASI 75 responses upon restarting tildrakizumab.

The findings from the two studies added to the of the phase III , which showed that two-thirds of patients treated with tildrakizumab attained PASI 75 response at 12 weeks compared with 48% of etanercept-treated patients. About three-fourths of patients treated with either of two doses of tildrakizumab attained PASI 75 by week 28, compared with 54% of the etanercept group.

Clinical development of IL-23 inhibitors for psoriasis initially focused on the p40 fragment, which is shared with IL-12. More recently, attention turned to p19, which is specific to IL-23. The increased specificity could lead to improved activity and response without sacrificing safety, said Reich.

The analysis of patients who switched from etanercept has considerable relevance for clinical practice.

"Many of us have patients on biologics that we've used in the past, and when these drugs fail, we often switch patients to another biologic," said Reich. "Having an idea of what to expect after switching a patient would be very useful."

Participants in reSURFACE 2 were randomized to one of two doses of tildrakizumab, placebo, or etanercept. The trial had co-primary efficacy endpoints of PASI 75 and PGA 0/1 response, both assessed at 28 weeks.

Patients who did not achieve PASI 75 response by 28 weeks had the option to switch to the higher dose (200 mg) of tildrakizumab and continue treatment to week 52, receiving tildrakizumab at weeks 32, 36, and 48. Reich said 57% of etanercept-treated patients attained PASI 75 responses, and 51% attained PGA 0/1 responses.

At 52 weeks, 81.4% of the 120 patients had met the endpoint of PASI 75 response, and 68.5% attained PGA 0/1 responses. Additionally, 41.6% of the patients attained PASI 90 responses and 15.9% attained PASI 100 responses.

For comparison, Reich cited results from the primary analysis of the reSURFACE 2 trial. Among patients randomized to tildrakizumab 200 mg, 74% had PASI 75 responses at 28 weeks, and 71% had PGA 0/1 responses. PASI 90 and PASI 100 responses at 12 weeks were secondary endpoints, and rates among patients allocated to tildrakizumab were 58% and 27%, respectively.

The second tildrakizumab report at AAD focused on a re-randomization component of , which involved 772 patients, allocated to the two doses of the IL-23p19 inhibitor or placebo. The trial design called for patients who attained PASI 75 response at 28 weeks with tildrakizumab to be randomized again to continue treatment to 64 weeks or discontinue, , of Probity Medical Research in Waterloo, Ontario, and colleagues reported in a poster presentation.

The results showed that 94% of patients who continued the 200-mg dose of tildrakizumab and 88% of those who continued the 100-mg dose maintained PASI 75 responses to week 64. Additionally, 57% and 49% of patients who discontinued the two doses of tildrakizumab maintained PASI 75 response to week 64. Among patients who discontinued tildrakizumab and relapsed (loss of PASI 75 response), 83.3% and 85.7 of patients in the 200- and 100-mg groups regained PASI 75 response after retreatment with their randomized doses of the drug.