Secukinumab was more effective than placebo in patients with psoriatic arthritis in a second phase 3 trial, strengthening the case for approval as a treatment for the disease.
Secukinumab (Cosentyx) treated psoriatic arthritis more effectively than placebo in a second phase 3 trial and strengthened its bid to be approved as a treatment for the disease.
A cohort of 606 patients received intravenous secukinumab (10 mg per kg of body weight) at baseline, 2 weeks and 4 weeks. Researchers then randomized the patients evenly to injections of placebo, 75 mg of secukinumab or 150 mg of secukinumab, administered every 4 weeks. Patients in the placebo group were switched to subcutaneous secukinumab at week 16 or 24, depending on clinical responses.
The primary endpoint of the trial was a 20% reduction from baseline to week 24 in the number of tender and swollen joints and at least 3 other important disease measurements, a standard known as an American College of Rheumatology 20 (ACR20) response.
Exactly half of the secukinumab 150 mg patients and 50.5% of the secukinumab 75 mg patients achieved ACR20 responses by 24 weeks, compared to only 17.3% of placebo patients (p<0.001 for superiority of both secukinumab doses over placebo).
“Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target,” the researchers who conducted the trial wrote in The New England Journal of Medicine. “Secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group. Improvements were sustained through 52 weeks.”
Infections such as candida were more common in both secukinumab groups than in the placebo group. Moreover, 4 patients in the 2 secukinumab groups (but no placebo-group patients) had a stroke during the course of the trial (0.6 per 100 patient-years; 95% confidence interval [CI], 0.2 to 1.5). Another 2 patients in the secukinumab groups (but no placebo-group patients) had a myocardial infarction during the trial (0.3 per 100 patient-years; 95% CI, 0.0 to 1.0).
Unfortunately, the researchers who ran the trial wrote, “The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use.”
The data from the new trial are consistent with findings from another phase 3 secukinumab study, which were published in The Lancet earlier this year.
The researchers who conducted that trial compared secukinumab with placebo in psoriatic arthritis patients for a year. A total of 100 patients received 300 mg injections, while 100 received 150 mg injections, 99 received 75 mg injections and 98 received placebo injections.
Fully 54% of the patients who received the 300 mg dose (p<0.0001) and 51% who received the 150 mg dose (p<0.0001) but only 15% of the patients in the placebo group achieved ACR20 after the 24th week of treatment.
The results, moreover, got better with time. By the 1-year point, 64% of the patients who received either the 300 mg dose or the 150 mg dose met ACR 20 response criteria. Also, 44% of the 300 mg patients and 39% of the 150 mg patients met the more demanding criteria of ACR 50.
The earlier trial results indicate that the compound works better in patients who have never been exposed to the current standard of care, drugs that inhibit the tumor necrosis factor (TNF) that plays a role in inflammatory response. Still, officials from Novartis, which has already gotten secukinumab approved in the US for the treatment of plaque psoriasis, believe the trial results indicate that secukinumab works well enough in patients who have already received anti-TNF therapy to be a viable option for patients who do not tolerate such medications well and for those who are not satisfied with their performance.