Secukinumab suppresses signs, symptoms of active ankylosing spondylitis

Ankylosing spondylitis, or AS, is the most common disease in a family of conditions known as spondyloarthritis. Spondyloarthritis is an inflammatory disorder affecting both the axial and peripheral skeleton. It involves bone and the synovium, and often occurs in the entheses, or sites where ligaments and tendons attach to bones. Symptoms of these diseases include inflammation and new bone formation that causes deformities. AS mainly affects the spine, tends to develop in young adults, and affects men more often than women. Frequency of AS in the United States is estimated at 0.5 percent.

A past Phase II study showed that secukinumab suppressed signs and symptoms of active AS after six weeks of treatment. New data from a Phase III study shows the drug's efficacy after 16 and 52 weeks of treatment, as well as achieving safety standards. Researchers based in the Netherlands, along with colleagues in England, France, Germany, the United States and Switzerland, conducted the research.

"The objective of the study was to evaluate the safety and efficacy of secukinumab versus placebo in patients with active AS, with a primary endpoint at 16 weeks. Additionally, this ongoing study will evaluate the long term safety and efficacy of secukinumab in AS, with the 52 week data presented," said Dominique Baeten, MD, PhD, professor of clinical immunology and rheumatology at the Academic Medical Center/University of Amsterdam in The Netherlands.

The researchers selected 371 randomized AS patients for the study. The mean age of the participants was 40.1-43.1 years. The mean disease duration of the patients was 6.5 to8.3 years, and their mean BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) score was 6.05-6.51. A little more than a quarter of the patients had had an inadequate response to existing anti-TNF agents to treat the signs and symptoms of their disease.

Patients were randomized to receive either IV secukinumab in 10 mg/kg doses at weeks 0, 2 and 4 followed by subcutaneous secukinumab at 75 mg or 150 mg doses every four weeks thereafter, or placebo according to the same IV and subcutaneous schedule. At week 16 of treatment, both active treatment groups had met the study's efficacy goals over the placebo group -- 59.7 percent of the first group and 60.8 percent of the second group met ASAS20 response levels compared to only 28.7 percent of the placebo group. Significant improvements in secondary measurements of AS signs and symptoms were also seen in patients taking both doses of secukinumab versus placebo at week 16 of treatment. The onset of action of secukinumab was rapid, with significant improvements in primary and secondary outcome parameters seen as early as one week of treatment, and those responses were sustained through week 52.

A significant improvement in signs and symptoms of AS was observed in both TNF blocker naïve patients and TNF blocker incomplete responders. Secukinumab was generally well tolerated by the patients with a safety profile consistent with that observed in the psoriasis and psoriatic arthritis clinical trial programs. The researchers concluded that secukinumab offers rapid, significant and sustained improvement of AS symptoms to patients regardless of their prior exposure to other TNF drugs. They further concluded that secukinumab is safe to use and well tolerated by AS patients.

"Secukinumab is the first drug achieving statistically and clinically significant therapeutic effects in phase III in AS since the introduction of TNF blockers," said Dr. Baeten. "The efficacy, safety and tolerability profile of secukinumab in AS was confirmed in an independent phase III placebo-controlled trial with subcutaneous dosing of secukinumab. Taken together, these data indicate that secukinumab may become a very useful alternative for TNF blockade in patients with active AS."