Twice-monthly psoriasis biologic shows promise

For adults with plaque psoriasis who find etanercept's twice-weekly dosing challenging, certolizumab may provide equivalent relief with a twice-monthly dosing regimen, shows a study published online April 13 in the Journal of the American Academy of Dermatology.

While there are other safe and effective TNF blockers, some patients fail one or both of self-injected TNF blockers etanercept and adalimumab, said Mark Lebwohl, M.D., the study’s first author who is of Mount Sinai School of Medicine, New York. Infliximab infusions may be an option, but it’s not for every patient. “We now have a superb TNF blocker which has data that are as good as or better than the other TNF blockers out there," he said.

Certolizumab may have a major impact for female patients of childbearing potential who are currently treated with available biologics even though they may cross the placental barrier. Many women stop treatment when they become pregnant, but they may not with certolizumab. "Certolizumab is a breakthrough in biologic therapy for psoriasis because this is the one drug we have that doesn't cross the placenta,” he said.

THE STUDY

This was a phase three study of adult patients with moderate-to-severe chronic plaque psoriasis who were randomized 3:3:1:3 to certolizumab 400 mg, 200 mg, or placebo every two weeks for 16 weeks or etanercept 50 mg twice-weekly for 12 weeks.

Certolizumab delivered statistically significant, clinically meaningful improvements in signs and symptoms of moderate-to-severe chronic plaque psoriasis versus placebo at weeks 12 and 16. The drug also maintained results at 48 weeks for patients who were re-randomized or continued with certolizumab.

Patients were randomized to certolizumab 400 mg every two weeks, 200 mg every two weeks (after 400 mg loading doses at weeks zero, two and four) or placebo (n = 167, 165 and 57, respectively). At weeks 12 and 16, all doses of certolizumab produced Psoriasis Area and Severity Index (PASI) 75 results significantly superior to placebo, with responder rates between 61.3 percent (certolizumab 200 mg at week 12) and 74.7 percent (certolizumab 400 mg at week 16). Clinically meaningful differences in PASI 75 responses occurred as early as week four, investigators noted.

Among secondary endpoints, the 400 mg dose proved superior, and the 200 mg dose proved noninferior, to etanercept 50 mg twice weekly in terms of PASI 75. Response rates at week 12 were 66.7 percent (p = 0.0152), 61.3 percent (p = 0.153) and 53.3 percent, respectively.

PASI 90 scores mirrored PASI 75 responses, with response rates ranging from 31.2 percent (200 mg at week 12) to 49.1 percent (400 mg at week 16). The proportions of patients reaching physician global assessment (PGA) scores of zero or one, with at least a two-point improvement from baseline, at weeks 12 and 16 ranged from 39.8-58.4 percent.

To assess the optimal certolizumab maintenance dose, investigators rerandomized PASI 75 responders in the certolizumab 400 mg and 200 mg groups to doses of 400 mg, 200 mg or placebo for 32 weeks beginning at week 16. Patients rerandomized to either certolizumab dose maintained PASI 75 response through week 48, with the best response occurring in patients who got 400 mg in both the initial and maintenance phases (98 percent), followed by patients who received 200 mg maintenance doses whether their initial dose was 200 mg (79.5 percent) or 400 mg (80 percent).

Even some week 16 PASI 75 responders rerandomized to placebo showed sustained response to treatment, with PASI 75 rates of 45.5 percent and 36.0 percent at week 48. This suggests that the duration of certolizumab's effect may extend well beyond withdrawal of treatment for some patients, wrote Lebwohl et al.

PASI 75 responders at week 16 in the etanercept group were rerandomized after a four-week washout period to certolizumab 200 mg (after three weekly loading doses of 400 mg). Among these patients, PASI 75 response at week 48 ranged between 72-82 percent.

Throughout the study, adverse events were consistent with the reported safety profile of certolizumab for other indications, and for TNF inhibitors in patients with moderate-to-severe plaque psoriasis. The most common treatment-related adverse events were infections and infestations, which occurred in around one-fourth of patients treated with either certolizumab or etanercept. One case of latent tuberculosis activation occurred in the etanercept cohort. Although certolizumab- and etanercept-treated patients had similar adverse-event totals through week 12, fewer certolizumab-treated patients (one in each of the 200 mg and 400 mg groups, versus four in the etanercept group) discontinued due to adverse events.

In terms of study limitations, etanercept treatment was single-blinded and lasted only 12 weeks. However, Lebwohl et al. wrote that they did not expect these conditions to affect treatment comparisons; furthermore, researchers used designated blinded efficacy assessors and other methods to minimize risk of bias.

DISCLOSURES
This study was funded by Dermira, Inc. in collaboration with UCB, Inc. UCB is the regulatory sponsor of 284 certolizumab pegol in psoriasis.

REFERENCE
Lebwohl M, Blauvelt A, Paul C, Sofen H, et al. “Certolizumab Pegol for the Treatment of Chronic Plaque Psoriasis: Results Through 48 Weeks of a Phase 3, Multicenter, Randomized, Double Blinded,
Etanercept- and Placebo-Controlled Study (CIMPACT),” Journal of the American Academy of Dermatology (2018), DOI: 10.1016/j.jaad.2018.04.013.