During the annual meeting, a standing-room-only audience attended a product theater on Cosentyx® (secukinumab), manufactured by Novartis, which is used to treat several forms of spondyloarthritis. Sergio Schwartzman, MD, of Weill Cornell Medical College and NewYork-Presbyterian Hospital and Hospital for Special Surgery, presented “Going Deeper into the Body of Evidence: Cosentyx for the Treatment of patients with AS, PsA, and PsO.”
Dr. Schwartzman noted that the field of rheumatology changed dramatically in 1998, when the first biologics were approved for rheumatologic diseases by the U.S. Food and Drug Administration. Since then, industry has created a number of agents for different targets in rheumatologic disease states. Secukinumab is the first and only drug approved as an anti–interleukin (IL)-17 therapy for three indications: ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis (PsO). The drug is a human monoclonal antibody that inhibits the action of IL-17A, which is overexpressed in people with spondyloarthritis.
The presentation reviewed the treatment’s important safety information and contraindications. Although Dr. Schwartzman stressed that there are no boxed warnings, he said patients receiving secukinumab have a slightly increased risk of infection, so physicians should monitor patients for signs of infection throughout treatment, in addition to pre-testing patients for tuberculosis. Also, Dr. Schwartzman cautioned that IL-17 is overexpressed in the bowels of patients with inflammatory bowel disease (IBD), so studies have found a trend of worsening IBD with secukinumab.
Secukinumab for AS
Inflammatory back pain caused by sacroiliitis and inflammation at other locations in the axial skeleton is the main clinical feature in patients with AS, Dr. Schwartzman said. Patients experience spinal stiffness, often in the morning, as well as loss of spinal mobility. Disease-related factors significantly impact their health-related quality of life, he said, but diagnosis is often delayed by 8 to 12 years because patients see primary care physicians and specialists such as orthopaedists first.
In the MEASURE 2 study, which assessed the efficacy and safety of secukinumab in patients with active AS, up to 68% of patients had reduced disease activity at week 16, with improvements in spinal mobility and quality of life. Follow-up studies found a consistent response rate at 4 years. In addition, inflammation dropped as measured by high-sensitivity C-reactive protein levels at week 16 and at 4 years. Patients achieved inactive disease as early as 1 year, which was sustained through 4 years.
The most common safety issues associated with secukinumab were increased rates of nasopharyngitis, upper respiratory tract infections, and nausea. Serious infections are possible, Dr. Schwartzman said, so patients should be monitored. For example, Crohn’s disease and ulcerative colitis can occur, but this is rare. Secukinumab’s safety profile remained consistent through 4 years.
Secukinumab for PsA
PsA contains multiple different phenotypes, Dr. Schwartzman said, and patients experience significant effects on morbidity and functional status. They also are at risk for structural damage. He reviewed results from the FUTURE 2 and FUTURE 5 clinical trials, which studied safety, tolerability, and efficacy of secukinumab in patients with active PsA.
Patients experienced quick relief compared with placebo as early as the third week of treatment, and they maintained strong response rates at 4 years, he said. They also had significant improvements and high rates of complete resolution of enthesitis and dactylitis through 4 years. Furthermore, radiographic data showed inhibition of structural progression.
Dr. Schwartzman said, the most common adverse events were nasopharyngitis, upper respiratory tract infection, headache, nausea, and hypercholesterolemia.
Secukinumab for PsO
The final study reviewed during the presentation examined secukinumab in PsO. The ERASURE and FIXTURE studies examined the efficacy and safety of secukinumab in moderate to severe chronic plaque-type PsO. Researchers documented significant clearance of the skin, and safety was similar to that observed in the other disease states. Efficacy and safety were maintained through 52 weeks. The TRANSFIGURE study has demonstrated secukinumab’s efficacy in nail psoriasis, Dr. Schwartzman said, although results can appear slow because damaged nails need a year to regenerate and get back to normal.
Secukinumab is administered via SensoReady® Pen45, which features no-push activation, a concealed needle, and a viewing window to ensure complete delivery of the medication. Recommended dosing is as follows, Dr. Schwartzman said:
- The medication is given once a week for 5 weeks, then every 4 weeks thereafter.
- Patients with AS: 150 mg with or without a loading dose
- Patients with PsA without moderate to severe PsO: 150 mg, with possible escalation to 300 mg, with or without a loading dose. This can be done with or without methotrexate, he said.
- Patients with moderate to severe PsO with or without PsA: 300 mg in two subcutaneous 150 mg injections; 150 mg may be acceptable in some patients, he said.
Dr. Schwartzman concluded by saying that secukinumab has demonstrated efficacy across several disease manifestations. Patients with AS showed improvement in axial disease as early as 4 weeks, as well as increased mobility, and response rates have been consistent through 4 years. In PsA, the treatment has improved multiple domains. Regarding peripheral arthritis, patients had strong response rates as early as 3 weeks, and response lasted through 4 years. In addition, the treatment inhibited progression of joint structural damage at 1 year. Patients with PsA also had complete resolution of enthesitis and dactylitis at 1 year and through 4 years. Finally, most patients with plaque PsO had clear or almost clear skin at week 12 of treatment; those with moderate to severe nail PsO saw a reduction at week 16 and through week 132.
In addition, the newest research has found that responses are enduring through 4 years, with similar safety profiles.