Secukinumab Shows High and Sustained Efficacy in Nail Psoriasis

2.5-year Results From the Randomized Placebo-controlled TRANSFIGURE Study

K. Reich; J. Sullivan; P. Arenberger; S. Jazayeri; U. Mrowietz; M. Augustin; B. Elewski; R. You; P. Regnault; J.A. Frueh

Disclosures

The British Journal of Dermatology. 2021;184(3):425-436. 

In This Article

Discussion

TRANSFIGURE is the first large randomized controlled trial to report long-term results in patients with nail psoriasis. As previously reported, at week 16, the study achieved its primary objective as both doses of secukinumab (150 mg and 300 mg) demonstrated superior efficacy compared with placebo in the treatment of patients with moderate-to-severe nail psoriasis. These improvements continued over time and the efficacy of secukinumab was sustained following long-term treatment with secukinumab up to 2·5 years.

The results of the TRANSFIGURE study demonstrated that secukinumab therapy is not only effective in long-term skin clearance, but also provides long-term sustainability of treatment effect in nail psoriasis. A mean NAPSI improvement from BL of −73·3% and −63·6% was achieved at 2·5 years with secukinumab 300 mg and 150 mg, respectively. A few studies in nail psoriasis have been reported with other treatments that show efficacy but demonstrate a lower improvement in comparison with secukinumab. In a recent study, adalimumab showed a significant improvement in total NAPSI (−56·2% vs. −11·5%, P < 0·001) vs. placebo at week 26,[30] although few patients achieved completely unaffected nails (6·6% at 26 weeks). Apremilast also showed improvement at week 16, with mean percentage change in NAPSI score of −10·5% in the placebo group and −28·9% in the apremilast group (P = 0·12). Continued improvement in NAPSI score was seen in patients who remained on apremilast treatment through week 52.[31] In another recent study published by van de Kerkhof et al.,[32] a subgroup analysis that included only patients with baseline fingernail psoriasis, ixekizumab provided significant improvement in fingernail psoriasis as early as week 2, with both dosing regimens demonstrating significantly greater NAPSI improvement (ixekizumab every 4 weeks, −36·7%; ixekizumab every 2 weeks, −35·2%) than either placebo (−34·3%) or etanercept (−20·0%) at week 12. This effect continued throughout 60 weeks of treatment.[32] In another study,[33] a significant proportion of patients treated with guselkumab achieved a Physician's Global Assessment for Fingernail Psoriasis score of 0 or 1 vs. adalimumab at week 48. However, a similar mean improvement from BL in NAPSI was observed in both groups. Secukinumab is the only drug that has shown long-term sustainability of response and this is an element of complete treatment.

TRANSFIGURE is the first study to demonstrate that an initial substantial improvement in total NAPSI scores has a durable response of up to 2·5 years. By directly inhibiting IL-17A, secukinumab acts downstream of all possible alternative pathways of IL-17A release and is able to inhibit this cytokine irrespective of the cell source. The reason for potentially being particularly efficacious with a durable treatment effect in nails may be due to the fact that other biologics target upstream cytokines (e.g. anti-tumour necrosis factor or anti-IL-23), which may fail to target alternative pathways for IL-17A release, especially from innate immune cells.

Treatment with secukinumab 150 mg or 300 mg resulted in sustained long-term efficacy across all secondary and exploratory efficacy endpoints assessed. The percentage decrease from BL in NAPSI score observed at week 16 in the secukinumab 150-mg and 300-mg groups continued to decrease further (indicating improvement of nail psoriasis disease severity) in Treatment Period 2 and was generally sustained over 2·5 years. Visible progressive improvement was observed for both secukinumab 150 mg and 300 mg over time up to 2·5 years. The percentage of patients who achieved almost clear nail psoriasis (NAPSI 0–2) increased over time up to 2·5 years for both treatment arms. The proportion of responders who achieved PASI 75/90/100 and IGA mod 2011 0/1 increased at the end of week 16 with both doses, indicating an improvement in psoriasis skin lesions; thereafter, response rates were sustained through 2·5 years.

Consistent with the observed improvements over BL in all efficacy parameters following long-term treatment with secukinumab, sustained improvements were also observed for all HRQoL measures assessed across both treatment groups. NAPPA-PBI mean scores observed at week 16 were sustained and improved further up to 2·5 years, demonstrating a considerable patient benefit from secukinumab treatment. More than half of patients achieved a DLQI score of 0/1, indicating no impact of psoriasis on patient QoL, which was sustained up to 2·5 years. Similarly, patients' HRQoL, as assessed by generic EQ-5D, continued to improve over 2·5 years during treatment. Patients had less impairment owing to their nail psoriasis in their day-to-day activities, walking, self-care and anxiety.

Secukinumab was well tolerated at both doses (150 mg and 300 mg) during treatment up to 2·5 years. The overall safety profile was consistent with that of previous secukinumab phase III trials in patients with psoriasis, and there were no new or unexpected safety signals following long-term administration of secukinumab 150 mg or 300 mg. There were no dose-dependent increases in the incidence of AEs between the secukinumab groups.

In conclusion, secukinumab treatment demonstrated strong, sustained and clinically meaningful efficacy, with a large improvement in QoL and a favourable safety profile for up to 2·5 years in patients who have moderate-to-severe psoriasis with significant nail involvement. The results from the current study re-emphasize that secukinumab is an efficacious treatment for multiple manifestations of psoriatic disease, including nails, scalp, palms/soles and joints, and provides patients and physicians with a long-term complete treatment option.

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