Long-term Secukinumab Effective for Ankylosing Spondylitis

Marcia Frellick

October 26, 2018

CHICAGO — For patients with ankylosing spondylitis, secukinumab (Cosentyx, Novartis) is well tolerated, and no new safety concerns emerged in a 3-year extension study (NCT01863732).

Data from the study show that the effectiveness of secukinumab is maintained over 5 years, which is important because "we need to not only have a fast response, but also a long-term response," said Xenofon Baraliakos, MD, from the Rheumazentrum Ruhrgebiet and Ruhr University Bochum in Herne, Germany.

Xenofon Baraliakos presenting the study at ACR 2018.

Many patients don't reach achieve remission with current therapies. "That's why we need different targets in this disease," he said during a late-breaking poster session here at the American College of Rheumatology 2018 Annual Meeting.

Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17-A. TNF inhibitors and secukinumab are the only biologic disease-modifying antirheumatic drugs approved for the treatment of ankylosing spondylitis.

In their 3-year extension, Baraliakos and his colleagues assessed 274 patients who continued treatment after the phase 3 MEASURE 1 study (NCT01358175).

Participants in the 2-year MEASURE 1 study were randomized to secukinumab — 10 mg/kg administered intravenously at baseline, week 2, and week 4, followed by 75 mg or 150 mg administered subcutaneously every 4 weeks thereafter — or placebo. At week 16, nonresponders in the placebo group were switched to one of the secukinumab groups; at week 24, responders were switched.

The extension was completed by 84.4% of patients in the 150 mg group and by 83.6% of those in the 75 mg group.

At week 64 of the extension, 82 patients in the low-dose group were switched to the high-dose group. Responses in these patients improved after the dose escalation.

That tells me we are at exactly the right dose with 150 mg.

"That tells me we are at exactly the right dose with 150 mg," Baraliakos told Medscape Medical News.

For study participants whose response to previous TNF inhibitor therapy was inadequate, "50% showed a good response" to secukinumab, Baraliakos reported.

It is unclear why some of the patients who switched to secukinumab did not respond, he said, adding that he would like to see if a combination of TNF and IL-17 inhibitors would be more effective in those patients.

Overall, though, "secukinumab provided sustained efficacy across multiple domains of AS, including signs and symptoms, physical function, and objective markers of inflammation through 5 years," the researchers write in their abstract.

Safety was reported for the 360 patients who received at least one dose of secukinumab. The exposure-adjusted incidence rate per 100 patient-years for ulcerative colitis was 0.1, for Crohn's disease was 0.6, for uveitis was 1.8, and for malignant or unspecified tumors was 0.5.

Disagreement About Dose

This alternative to TNF inhibitors adds an option for patients, said Sergio Schwartzman, MD, from Weill Cornell Medicine and Hospital for Special Surgery in New York City.

"There are no other anti-IL-17 antibodies approved for ankylosing spondylitis," Schwartzman explained, "so with regard to the uniqueness of this therapy for this condition, it stands alone."

The fact that no new safety signals emerged in this study of real-world use in a large number of patients, for this kind of study, is good news.

"Having data that support what we see in the real world clinically is helpful," he told Medscape Medical News.

Although TNF inhibitors can be effective in ankylosing spondylitis, "in clinical trials, close to 50% of people treated with anti-TNF drugs don't respond. We needed an alternative; this gives us options," Schwartzman noted.

Physicians will continue to choose therapies on the basis of evidence, what insurance will cover, and personal preference, he said. Unfortunately, there are no biomarkers to indicate whether a person will respond to a certain class, he added.

But Schwartzman disagrees with Baraliakos about the 150 mg dose.

"Most people think this is not the right dose. The dose for psoriasis and psoriatic arthritis is either 150 mg or 300 mg," he explained. Studies are being conducted on the 300 mg dose, and "I would venture to guess that it improves efficacy because it definitely does in psoriasis and it probably does in psoriatic arthritis."

The study was funded by Novartis. Schwartzman consults for and has received speaker fees from Novartis. His coauthors report financial relationships from Abbott, AbbVie, Amgen, BMS, Boehringer, Bristol-Myers Squibb, Celgene, Celltrion, Centocor, Chugai, Genentech, Horizon, Janssen, Medac, Merck, MSD, EBEWE Pharma, Eli Lilly, Mundipharma, Novartis, Pfizer Roche, Sanofi-Aventis, Sun Pharma, and UCB .

American College of Rheumatology (ACR) 2018 Annual Meeting: Abstract L13. Presented October 22, 2018.

Follow Medscape Rheumatology on Twitter @MedscapeRheum and Marcia Frellick @mfrellick

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