BERLIN – The tumor necrosis factor inhibitor certolizumab pegol significantly lessened both joint and skin symptoms of psoriatic arthritis in a pivotal phase-III clinical trial.
"This will be the basis for seeking regulatory approval for this drug in the treatment of psoriatic arthritis. It’s a very important development because we don’t have quite the armamentarium of drugs for treating psoriatic arthritis that we do in treating rheumatoid arthritis," Dr. Philip J. Mease observed when he presented the results of the study, known as RAPID-PsA, at the annual European Congress of Rheumatology.
The ACR 20, ACR 50, and ACR 70 responses (that is, 20%, 50%, and 70% improvements, respectively, in certain parameters specified by the American College of Rheumatology) to certolizumab were two- to fourfold higher than in placebo-treated controls. Also impressive were the proportion of certolizumab-treated patients with at least a PASI 75 (that is, a 75% improvement in the Psoriasis Area and Severity Index), as well as the documented improvement in physical functioning. But perhaps most striking of all was the kinetics of the response to certolizumab.
"As early as 1 week with this agent, it separates from placebo. There’s a very fast onset of action with certolizumab," noted Dr. Mease of the University of Washington, Seattle.
The 24-week, three-armed, phase III, double-blind clinical trial included 409 psoriatic arthritis (PsA) patients. They were randomized to placebo or to a loading dose of 400 mg of subcutaneous certolizumab (Cimzia) at weeks 0, 2, and 4, then were further randomized to continue certolizumab at either 200 mg every 2 weeks or 400 mg every 4 weeks.
These patients had severe PsA, with a mean baseline of 20 tender and 11 swollen joints. Nearly two-thirds of subjects had enthesitis and one-third had dactylitis. Their median baseline PASI was in the 7-8 range, with C-reactive protein levels ranging from 7 mg/L to 9 mg/L. All subjects had failed at least one disease-modifying antirheumatic drug, and about half had failed two or more. Moreover, 20% of subjects had previously received a TNF inhibitor that over time had become ineffective.
"That makes it presumably tougher to achieve the kinds of responses we see in most other trials where patients are required to be naive to anti-TNF medications. But this design more approximates a real-world situation in which some of the patients you’re treating receive certolizumab as first-line therapy, but others may receive it as second- or third-line anti-TNF medication," the rheumatologist explained.
The ACR 20 response to the pegylated humanized TNF inhibitor at week 12 (the prespecified primary study end point) was closely similar in the twice-monthly and once-monthly dosing groups, as was the ACR 50 response. However, the twice-monthly 200-mg regimen was superior at achieving ACR 70. (See box.)
Skin responses were "quite robust," Dr. Mease declared. At week 12, among patients with at least 3% body surface area involvement at baseline, PASI 75 responses were documented in 47% of patients in either of the certolizumab arms, compared with 14% of placebo-treated controls. At week 24, PASI 75 responses were noted in 62% of patients on twice-monthly certolizumab, in 61% of those on once-monthly therapy, and in 15% of controls.
Improved physical functioning was reflected in a mean 0.54-point reduction at week 24 from a mean baseline HAQ-DI (Health Assessment Questionnaire-Disease Index) score of 1.3 in the twice-monthly certolizumab group and a 0.46-point decrease with once-monthly therapy, both of which were well beyond the 0.35-point reduction threshold conventionally deemed to be a minimally clinically important improvement. In contrast, HAQ-DI scores decreased by a mean of only 0.19 points in the control group.
Dr. Philip J. Mease
Side effects were the same as those seen in the treatment of rheumatoid arthritis, for which certolizumab is approved in the United States and Europe with the same dosing choices.
"No new safety news," Dr. Mease commented.
He noted that he was presenting a first look at the RAPID-PsA results. Later this year at the annual meeting of the American College of Rheumatology, he and his coinvestigators will be able to share the results of ongoing analyses of the radiographic response to treatment, as well as certolizumab’s ability to treat enthesitis and dactylitis.
Dr. Mease predicted that the dosing that’s ultimately approved for PsA will mimic that used in RA, offering patients the flexibility to choose between once- and twice-monthly therapy.
Psoriasis occurs in about 2.1% of the general population worldwide. Roughly 30% of affected patients also have PsA.
"This is one of the most devastating diseases a person can have because not only does it feature the functional impairment of a musculoskeletal disease but also the embarrassing cosmetic problems of psoriasis. Psoriatic arthritis is one of the few diseases we work with in rheumatology where suicide is one of the reasons for increased early mortality," Dr. Mease said.