The interleukin (IL)-17A inhibitor secukinumab (Cosentyx) provided durable benefits in the treatment of psoriatic arthritis, and patient satisfaction with self-administration using an autoinjector was high, researchers found.
At week 24 in a phase III trial known as FUTURE 3, improvements of at least 20% on the criteria of the American College of Rheumatology (ACR20) were seen in 48.2% of patients receiving 300 mg of secukinumab every 4 weeks and in 42% of those receiving 150 mg, compared with 16.1% of those given placebo (P<0.0001), according to Peter Nash, MD, of the University of Queensland in Brisbane, Australia, and colleagues.
Week 24 was the end of the placebo-controlled phase of the study. By week 52, when all patients were receiving the active treatment, ACR20 response rates rose to 58.3% and 47.1% in the 300- and 150-mg groups, respectively.
And at least 88% of patients said that they were satisfied or very satisfied with the autoinjector, finding it easy or very easy to use, the researchers reported in Arthritis Research & Therapy.
The efficacy findings confirm what has previously been seen in other phase III trials of subcutaneous secukinumab. For example, in a study known as FUTURE 1, published in 2015 in the New England Journal of Medicine, ACR20 responses at week 24 were observed in 50% of patients receiving 150 mg monthly and in 50.5% of those receiving 75 mg. In FUTURE 2, published the same year in The Lancet, 54% of patients receiving 300 mg had ACR20 responses at week 24, as did 51% of those given 150 mg.
FUTURE 3 is an ongoing randomized trial being conducted at 74 centers worldwide. Participants have active disease, defined as at least three tender and swollen joints, and could have previously received up to three tumor necrosis factor (TNF) inhibitors.
A total of 414 patients were enrolled. Mean age was 50, slightly more than half were women, and more than 90% were white. Mean time since the diagnosis of psoriatic arthritis ranged from 6.6 to 8.3 years, and one-third had previously received a TNF inhibitor. Mean number of tender and swollen joints were 21 and 10, respectively.
Almost half were using methotrexate at baseline.
In general, patients who were anti-TNF naive fared better. At week 24, the ACR20 and ACR50 responses among patients who were anti-TNF naive were 51.6% and 45.7% in the 300 mg and 150 mg groups, respectively, while in patients who had previously had an inadequate response to anti-TNF treatment, the response rates in the two dosage groups were 40.9% and 34.1%.
The greater responses seen with the higher dose among patients with previous anti-TNF exposure suggests that the 300 mg dose is appropriate for these refractory patients, the authors indicated.
On the Psoriasis Area and Severity Index (PASI), improvements of 75% were seen in 61.3% and 55.9% of the 300- and 150-mg groups at week 24, compared with 11.9% of the placebo group. At week 52, PASI75 responses were seen in 74.2% of the 300-mg group and in 60.3% of the 150-mg group.
On the Health Assessment Questionnaire-Disability Index (HAQ-DI) changes from baseline at week 24 were -0.38 in the 300-mg group and -0.27 in the 150-mg group compared with -0.17 in the placebo group, and mean changes in pain scores were -18.23 and-12.46 versus -3.75. At week 52, changes from baseline on the HAQ-DI were -0.43 and -0.30 in the 300 mg and 150 mg groups, while changes in pain scores were -20.3 and -11.8.
During the 52 weeks, the incidence rates of adverse events were 194.9 and 192.5 per 100 patient-years, while the rates of serious adverse events were 8.8 and 10.2 per 100. Two deaths occurred — one pancreatic cancer and one small cell lung cancer.
Candida infections were an adverse event of special interest, because IL-17 plays a crucial role in mucocutaneous defense against fungal and bacterial infections. Oral candidiasis was reported in three patients in the 300-mg group and five patients in the 150-mg group, and two patients in each dose group experienced vulvovaginal candidiasis. Patients on secukinumab should be observed closely for Candida infections, the researchers noted.
Neutropenia developed in two patients in the 150-mg group and one patient in the 300-mg group.
“In summary, self-administration of subcutaneous secukinumab provided sustained improvements at 52 weeks across multiple clinical domains in patients with active psoriatic arthritis,” Nash and colleagues concluded, adding that patients were satisfied with the autoinjector device.
A limitation of the study was the lack of a placebo control after week 24.
The study was funded by Novartis Pharma.
The authors reported financial relationships with Novartis, AbbVie, Roche, Pfizer, Bristol-Myers Squibb, Janssen, Celgene, Crescendo Bioscience, Genentech, Eli Lilly, Merck, UCB, and Amgen. Several are employees of Novartis.