SLR - July 2019 - Cindel X. Harris
Reference: Mease, Philip J., et al. “Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis.” New England Journal of Medicine, vol. 373, no. 14, 2015, pp. 1329–1339., doi:10.1056/nejmoa1412679.Scientific Literature Review
Reviewed By: Cindel X. Harris, DPM
Residency Program: East Liverpool City Hospital – East Liverpool, OH
Podiatric Relevance: Psoriatic arthritis is a systemic inflammatory process that promotes deformities in bony and soft tissue structures. This includes dactylitis that affect the digits, and enthesitis that affects common structures like the Achilles. Inflammation in the Achilles can lead to tenodesis and eventually rupture, as has been show in prior studies. This article shows that secukinumab can help decrease the inflammatory response and comorbidities associated with psoriatic arthritis.
Methods: This is a double-blind, phase three study. Six hundred and six patients with psoriatic arthritis were randomly assigned 1:1:1 ratio to receive intravenous secukinumab at weeks 0,2,4, followed by subcutaneous dose that varied different dosages or patient would receive the placebo. The primary outcomes were the proportion of patients with an American College of Rheumatology 20 (ACR20) response at week 24, defined as 20 percent improvement from baseline. They used Health Assessment questionnaire-disability index (HAQ-DI) which helped determine the amount of inflammation - the higher the score, the more it correlated with the C-reactive protein and erythrocyte sedimentation rate. Higher inflammatory reaction is correlated with structure damage such as with enthesitis and dactylitis.
Results: Five hundred fifty-three out of the 606 patients completed the 24-week period. At week 24 patients responded significantly higher with the doses of 150mg (50.0 percent) and 75mg (50.5 percent) than those receiving the placebo (17.3 percent). Secondary outcomes include decrease in joint structural damage with groups that used secukinumab. The outcomes that were most affected were dactylitis (53.5 percent) and enthesitis (61.4 percent).
Conclusions: Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates inhibition of interleukin-17A as a therapeutic target. This helped decrease the inflammatory process that causes structural damage. On the contrary, infections are common in the secukinumab and patients would get candida because of their weakened immunity. Inflammation is part of the healing process and if secukinumab lowers immunity, this can promote tumor like cells that can lead to cancer in the future. On the other hand, decrease in structure damage and bone deformity can promote a better quality of life. Further studies on the effect of using secukinumab for long term use needs to be assessed for adverse events.