continued to demonstrate superior efficacy relative to RAN (PASI-75 responses of 83.0% and 46.6%, respectively).During its 4th year, the SCULPTURE study transitioned to an open-label, home-administration design.24 In an observed data analysis, the 300 mg group exhibited a PASI-75 response rate of 88.5%, PASI-90 rate of 66.4%, and PASI-100 rate of 43.5%. The average PASI improvement was 90.8%, which has consistently remained >90% over the 4-year period. Patients experienced a substantial and lasting reduction in disease symptomatology, with 70.8% indicating that they do not suffer any impact on their quality of life. The safety profile has remained favorable, without increases in adverse events over time.The development of immunogenicity remains an important consideration in the use of biologics. Reich et al.25 examined the immunogenicity of secukinumab over several clinical trials in subjects followed up to 60 weeks. Patients treated with secukinumab for plaque psoriasis were monitored for antidrug antibodies (ADAs) at baseline and weeks 12, 24, 52, and 60. Among 2842 patients, only 0.4% developed ADAs from treatment, demonstrating the low immunogenicity of secukinumab. Importantly, these neutralizing antibodies were scarce for patients treated with FI dosing or RAN dosing and were not correlated with a loss of efficacy. Such results show promise for secukinumab in maintaining clinical responses over time.Treatment of Palmoplantar PsoriasisPalmoplantar psoriasis may affect up to 40% of psoriasis patients and remains notoriously resistant to treatment.26 The GESTURE trial (ClinicalTrials.gov/NCT01806597) evaluated secukinumab in the treatment of moderate-to-severe palmoplantar psoriasis.27 The study randomized 205 subjects to treatment with either secukinumab 300 mg, 150 mg, or placebo. At week 16, the percentage of patients who achieved an Investigator Global Assessment (IGA) of 0 or 1 (clear or almost clear) was 33.3% in the secukinumab 300 mg group, 22.1% in the secukinumab 150 mg group, and 1.5% in the placebo group (P less than .001 versus secukinumab groups).Follow-up data at 1.5 years revealed a durable response, with 57% of patients who received secukinumab 300 mg achieving an IGA of 0 or 1.28 The safety profile was comparable to previously reported secukinumab trials. Although lacking an active comparator, the GESTURE study demonstrated high rates of efficacy in treating palmoplantar psoriasis.Treatment of Nail PsoriasisNail involvement is common in psoriasis, with a prevalence estimated at roughly 40% to 80% of psoriasis patients.29-31 Studies have shown that over half affected patients report pain due to nail changes, with many noting restrictions in their daily activities or work as a result of the disease.32The TRANSFIGURE trial (ClinicalTrials.gov/NCT01807520) examined secukinumab in the treatment of nail psoriasis.33 Patients with moderate-to-severe plaque psoriasis and significant nail involvement were randomized to treatment with either secukinumab 300 mg, secukinumab 150 mg, or placebo. Changes in nail involvement were measured using the Nail Psoriasis Severity Index (NAPSI). At week 16, NAPSI scores improved by 45.3% in the 300 mg group, 37.9% in the 150 mg group, and 10.8% in the placebo group (P less than .0001 versus secukinumab groups). The high rates of efficacy continued over time, with week 32 results showing 63.2% improvement in the 300 mg group.Nail psoriasis has also been examined in the FUTURE-2 study (ClinicalTrials.gov/NCT01752634). (34) The trial evaluated patients with active psoriatic arthritis who were randomized to treatment with secukinumab 300 mg, 150 mg, 75 mg, or placebo. Changes in nail disease were assessed with the modified NAPSI (mNAPSI). At week 24, the 300 mg group showed 10.30% improvement in mNAPSI scores, compared to 4.85% in the placebo group (P less than .01).
Phase III clinical trials have established the long-term safety and efficacy of secukinumab in the treatment of moderate-to-severe psoriasis. Treatment has been associated with a modest increase in non-serious monilial infections (1.2% with 300 mg versus 0.3% with placebo),35 which is to be expected given that IL-17 is involved in host defense against fungal pathogens. With 4-year data now available, the clinical benefits of secukinumab have been shown to remain consistent over an extended timeframe, without increases in safety signals. No risks of malignancy, major adverse cardiac events, depression, or tuberculosis reactivation have been found. To date, secukinumab is the only IL-17A inhibitor to demonstrate these results through such prolonged follow-up. Of particular importance, secukinumab has shown to be effective in palmoplantar psoriasis, a challenging disease. The success of secukinumab reinforces the importance of IL-17A in the pathogenesis of psoriasis and the significance of selectively inhibiting this cytokine. Given its favorable safety profile, high efficacy, and monthly maintenance dosing schedule, secukinumab represents a key treatment option for patients affected by moderate-to-severe disease.