LONDON — Secukinumab has been shown to be effective for the treatment of moderate-to-severe plaque psoriasis in hard-to treat population of patients who had failed to respond to anti-tumour necrosis factor-α treatment, and to have a favourable safety profile.
Although the vast majority of clinical trials contain some biologic exposed patients, they usually make up a minority of patients and do not report why patients who had previously received a biologic or had stopped. The aim of the SIGNATURE study, sponsored by Novartis, was to test whether secukinumab, human anti-interleukin-17A monoclonal antibody, would be effective in people who have failed prior anti-TNF therapy.
The study involved 235 patients with moderate-to-severe chronic plaque psoriasis who had failed anti-TNF-α therapy; this meant they had either failed an anti-TNF-α therapy in the first 16 weeks of treatment, initially responded to an anti-TNF-α therapy but had subsequently failed, or that they belonged to a resistant cohort of patients who had failed multiple anti-TNF-α treatments.
As a result the characteristic so the patients were different to those seen in patients involved in pivotal phase 3 clinical – their average body weight and the length of time they had experienced psoriasis were both quite a lot higher, and almost 50% of them had psoriatic arthritis whereas in a pivotal phase 3 trial the proportion would be around 20%.
Patients received secukinumab as subcutaneous injections of 300 mg or 150 mg for a 16-week initiation period (weeks 0–4, 8, 12 and 16) followed by two maintenance periods up to 72 weeks.
The primary objective of the analysis of the results so far was to evaluate the PASI 75 response of the 300mg dose at week 16, and the secondary objectives were to look at the PASI 75 and 90 responses of secukinumab 150mg/300 mg after 16 weeks.
Presenting the results to the Psoriasis: From Gene to Clinic International Congress in London on Friday, Dr. Richard Warren of the University of Manchester and Royal Salford NHS Foundation Trust in the United Kingdom, said: “Secukinumab demonstrated efficacy in patients who had failed anti-TNFs and 65% achieved the primary endpoint of a PASI 75 at 16 weeks. We saw that if patients have failed multiple anti-TNFs then they did worse, but nearly 50% were still responding and I think that these data demonstrate very clearly that the 300mg dose is absolutely the right dose for our psoriasis populations.”
At 16 weeks 44.3% of patients receiving the 300mg achieved a PASI 75 and average Dermatology Life Quality Index (DLQI) score had fallen from 20.2 to 4.2. For the 150mg dose 44.3% patients achieved a PASI 75 and the DLQI fell from 19.1 to 6.7.
When the various subgroups were looked at in detail for the 300mg dose, the 16-week data revealed that 71.3% of patients who had failed an anti-TNF-α therapy in the first 16 weeks achieved a PASI 75, 70.5% of patients who had initially responded to an anti-TNF-α therapy but subsequently failed, and 47.7% of patients who were serial non-responders to anti-TNF-α therapy.
The safety profile raised no new or unexpected safety concerns at 16 weeks. Candida is a known risk on IL-17s and cases were seen in both dosage arms, with a slightly higher percentage in the 300mg arm. There were no new cases of inflammatory bowel disease or tuberculosis.
Dr. Warren said: “This was a brave study to do because rarely do we actually see clinical trials where patients have clearly failed or been documented to fail biologics, so although the results are a little more modest than we are used to this was an important study.”
R.B. Warren, J. Barker, D. Burden, A. Finlay, et al. “Efï¬cacy and safety of secukinumab in patients who have failed antitumour necrosis factor-α treatment from the U.K. and Republic of Ireland: Results of the SIGNATURE study,” Psoriasis: From Gene to Clinic International Congress, London , Dec. 1, 2017, 13.45. http://psoriasisg2c.com/wp-content/uploads/2017/11/Online-Psoriasis-G2C-... (page 66)