Secukinumab in the therapy of psoriasis and psoriatic arthritis: a safe choice in clinical practice

The IL17 signaling pathway plays a crucial role in the pathogenesis of both psoriasis and psoriatic arthritis. Therapeutic monoclonal antibodies targeting this cytokine or its receptor have therefore been developed, and proved effective and well tolerated in the treatment of these conditions, in both clinical trials and in real-world settings [1–9]. In the FUTURE-1 trial, analyzing 606 patients with psoriatic arthritis, during the 16-week placebo-controlled period, adverse events were reported in 64.9% of patients receiving secukinumab 150 mg, in 60.4% of those receiving the 75 mg dose, and in 58.4% of those receiving placebo [10]. Rates of nonfatal serious adverse events and discontinuations were similar across the study groups. Secukinumab treatment was associated with a higher prevalence of infections (especially of the upper airways) compared to placebo. Over 104-week treatment period (with a mean exposure to secukinumab of 627.1 days or 1,007.9 patient-years), type, incidence and severity of AEs were consistent with that reported at 52-week [11]. Exposure-adjusted rates of AEs were 199.4 per 100 patient-years (95% confidence interval [95% CI] 175.8–225.2) in those receiving secukinumab 150 mg, and 155.9 per 100 patient-years (95% CI 136.7–177.0) in those receiving 75 mg. AEs were mostly mild or moderate. Discontinuation due to AEs occurred in 3.4% and 5.8% of cases treated with 150mg and 75 mg secukinumab, respectively. The most common AEs were nasopharyngitis and upper respiratory tract infection. No treatment withdrawal was due to candida. Furthermore, neither new cases of active tuberculosis (TB), nor reactivation of latent TB occurred [11]. In the SCULPTURE study, secukinumab demonstrates high-sustained efficacy and a favorable safety profile in patients with moderate to severe psoriasis, through 5 years of treatment [8], with no increase in yearly AE rates from year 1 to year 5. Overall, no warning signals were identified and the safety profile was consistent with that established in the secukinumab phase 2/3 clinical program. Although patients with lower levels of IL-17, or in whom this cytokine is absent, are at higher risk of Candida and staphylococcus infection, the reported incidence of Candida infections in patients treated with secukinumab was 1.8% at year 1 and 0% at year 5, as reported in the SCULPTURE trial [8]. Moreover, several questions regarding secukinumab safety profile remain open, in particular, (i) in patients with comorbidities, mainly with high cardiovascular risk factors or cardiovascular comorbid conditions, (ii) on the potential risk of Candida infection or (iii) occurrence of inflammatory bowel diseases during anti-IL17 therapy.

In order to describe the emerging evidence on secukinumab safety profile in the real-world setting, we gathered the experience of Italian dermatologists, who reported an overall favorable response, also in difficult-to-treat cases, presenting multiple comorbid conditions. A case series by Papini et al did not reveal any increase in the occurrence of candidiasis in psoriatic patients treated with 300 mg secukinumab for one year. In this report, two patients who were positive for cutaneous Candida colonization prior to secukinumab therapy became negative in the following months without anti-fungal therapy. Lasagni et al., reported 3 cases, successfully treated with secukinumab, unresponsive to previous biological treatments, and presenting clinically significant comorbidities. Two secukinumab-treated patients experienced psoriasis improvement and maintained a normal hepatic function, despite their HBV or HCV positivity. The third psoriatic patient, also affected by obesity, non-alcoholic hepatosteatosis and NYHA class II heart failure, was treated with secukinumab without safety issues related to its use. Viapiana et al., reported two cases of psoriatic arthritis patients, intolerant to multiple biological agents, who was successfully treated with secukinumab resulting effective and safe in this bio-experienced patient. These preliminary findings suggest a satisfactory secukinumab safety profile, though confirmatory data from large cohorts of secukinumab-exposed patients observed in the long-term in a real-world setting are needed.

Andrea Chiricozzi
Dermatology Unit, Department of Clinical and Translational Medicine, University of Pisa, Pisa, Italy
[email protected]