The TNF alpha inhibitor certolizumab pegol (Cimzia, UCB) has achieved the highest response rates seen in phase three trials of self-injectable biologics for psoriasis.
The TNF alpha inhibitor certolizumab pegol (Cimzia, UCB) has achieved the highest response rates seen in phase three trials of self-injectable biologics for psoriasis, according to a study published online in the Journal of the American Academy of Dermatology (JAAD).
Certolizumab pegol was approved in May by the FDA for adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
The CIMPASI-1 and CIMPASI-2 trials showed that week 16 improvements in Psoriasis Area and Severity Index (PASI) and other measures persisted, and in some cases improved, through week 48. In pooled analysis, week 16 PASI 75 response rates for 200 mg and 400 mg doses were 76.7% and 82.0%, versus 70.7% and 83.6% at week 48.
Also at week 48, depending on study population (CIMPASI-1, CIMPASI-2 or investigators’ pooled analysis) and dose, 52.772.6 percent of patients achieved physician global assessment (PGA) scores of clear or nearly clear (0/1), including at least a two-point improvement from baseline. PGA 0-1 response rates at week 16 ranged between 47.0 percent (200 mg, CIMPASI-1) and 71.6 percent (400 mg, CIMPASI-2). PASI 90 response rates, reported only until week 16, were 35.8-55.4 percent.
In two separate multi-site trials whose results were published in the JAAD online on April 13, 2018, investigators randomized patients with moderate-to-severe psoriasis to treatment with certolizumab pegol 400 mg every two weeks, certolizumab pegol 200 mg every two weeks (after 400 mg loading doses at weeks zero, two and four) or placebo. At week 16, any patients on active treatment who had achieved PASI ≥ 50 continued at their original dose through week 48. Placebo-treated patients who had achieved PASI 50-74 at week 16 switched to certolizumab pegol 200 mg every two weeks (after loading doses). During the first 48 weeks of the ongoing study, injections were performed by study personnel who were not involved in any other study procedures.
While CIMPASI-1 results and pooled results revealed that the 400 mg dose generally performed better than 200 mg, CIMPASI-2 results showed no significant difference between the doses. In CIMPASI-1, for example, week 16 PASI 75 response rates were 66.5 percent (200 mg) and 75.8 percent (400 mg). The corresponding figures in CIMPASI-2 were 81.4 percent and 82.6 percent.
Investigators could not explain why CIMPASI-2 showed no significant differences between the two certolizumab pegol doses. “Several demographic and baseline clinical characteristic differences between the two studies were observed. However, there is no clear evidence to indicate these differences affected clinical outcomes across the studies,” wrote the authors of the study which was led by Alice Gottlieb, M.D., Ph.D., of New York Medical College at Metropolitan Hospital, New York.
Previous studies have suggested that patients with prior biologic exposure experience lower efficacy than biologic-exposure experience lower efficacy than biologic-naÃ¯ve patients do in clinical trials. In CIMPASI-1 and CIMPASI-2, however, PASI 75 and PGA 0/1 responses were similar in patients with and without prior antiTNF biologic use, a finding that authors noted is consistent with certolizumab pegol data in PsA trials.
“It is also notable that these improvements occurred in a population with a mean body mass index (BMI) > 30, since high BMI has been an observed negative predictor of biologic response,” wrote Gottlieb et al.
“Clinical-trial populations in psoriasis have similar baseline characteristics. So that’s exciting, to have a TNF blocker with a higher clinical response rate than what we’ve seen. I’m very excited about the data regarding lack of placental transfer and transfer into breast milk,”the authors wrote.
The data are already noted in the product’s package insert. “For women of reproductive potential, that, combined with the registry data on TNF blockers, makes it in my opinion a first choice for women (with psoriasis) who want to become pregnant.”
Certolizumab pegol’s safety profile in CIMPASI-1 and CIMPASI-2 was consistent with that of TNF inhibitors, the authors wrote.
While the studies’ combined sample size (461 patients) was smaller than populations used in prior pivotal ertolizumab pegol trials, “certolizumab has large amounts of data in Crohn’s disease, rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, indications for which it is already approved.” Hence the FDA and the drug’s manufacturer UCB agreed that certolizumab pegol’s safety had already been established.
The authors pointed to some limitations in the study, such as the lack of comparative studies with golimumab.
“One has to be careful about superlatives, because there are no comparative studies with adalimumab or etanercept. There is no psoriasis study comparing certolizumab against golimumab,” Dr. Gottlieb said.
Dermira and UCB funded CIMPASI-1 and CIMPASI-2. Dr. Gottlieb has received consulting and/or other fees from AbbVie , Allergan, Beiersdorf, Bristol-Myers Squibb, Celgene, Dermira, Incyte, Janssen, Lilly, Novartis, Reddy Labs, Sun Pharmaceutical Industries, UCB and Valeant.
Gottlieb AB MD, Blauvelt A MD, Thaci D MD, et al. “Certolizumab pegol for the treatment of chronic plaque psoriasis: results through 48 weeks from two phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2),” Journal of the American Academy of Dermatology. April 13,2018