1. In a posthoc analysis of 2, phase 3 randomized controlled trials of over 1000 patients with moderate-to-severe plaque psoriasis, tofacitinib (an oral Janus kinase inhibitor) treatment demonstrated significantly improved clinical nail psoriasis severity scores at 16 weeks compared to placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Psoriasis is a chronic, inflammatory skin disease associated with clinical manifestations of the nail that include pitting, onycholysis, subungual hyperkeratosis, and discoloration. Nail psoriasis may severely impair function and is associated with significantly greater disease severity and impact on patient quality of life than psoriasis without nail involvement. Tofacitinib is an oral Janus kinase inhibitor that has previously demonstrated efficacy and tolerability in phase 3 clinical trials of moderate-to-severe chronic plaque psoriasis. The purpose of this study was to assess the effect of tofacitinib on nail psoriasis.
This study is a post-hoc pooled analysis of two phase 3 clinical trials evaluating the efficacy of tofacitinib in 1196 patients with nail psoriasis. At the conclusion of the study, both the 5mg and 10mg twice-daily administrations of tofacitinb demonstrated clinically significant improvement in nail psoriasis compared to placebo at 16 weeks with effects maintained at 52 weeks. The results of this study support the use of tofacitinib as a potential treatment modality for nail psoriasis. This study is strengthened by its large sample size, multiple trial sites, randomization, double blinding, and comparison to placebo. The interpretation of study results is limited by the use of only objective measures to assess severity without incorporating subjective patient-reported outcomes. Moreover, non-responders were discontinued from the study at 28 weeks and not included in analysis. Multi-center prospective trials that include patient-reported outcome measures to assess improvements in severity may help improve the validity and of the study.
In-Depth [randomized controlled trial]: This study conducted a pooled posthoc analysis of two identical 52-week multi-site phase 3 randomized controlled trials evaluating the efficacy of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis with nail involvement. Patients in both trials were randomized 2:2:1 to receive tofacitinib 5mg or 10mg, or placebo twice daily. Overall, this study identified 1196 patients with nail involvement of the original 1859 patients with psoriasis recruited in the initial studies. Patients were determined to be moderate-to-severe via a Psoriasis Area and Severity Index score ≥12, Physician’s Global Assessment of moderate or severe, and affected body surface area ≥10%. Improvements in severity were assessed using the Nail Psoriasis Severity Index (NAPSI). The proportion of patients that demonstrated a 50%, 75% or 100% reduction from baseline in NAPSI score (NAPSI50, NAPSI75 and NAPSI100) were calculated and compared between treatment arms. Patients treated with tofacitinib demonstrated improvement in pitting, onycholysis, subungual hyperkeratosis, and discoloration. Moreover, treatment with tofacitinib demonstrated significantly greater proportions of patients that achieved NAPSI50, NAPSI75 and NAPSI100 compared to placebo at 16 weeks (p < 0.05). Furthermore, the mean number of affected nails decreased from 7.3 at baseline to 3.5 and 2.7 at 52-weeks for the 5mg and 10mg doses, respectively.
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