Adalimumab for nail psoriasis: efficacy and safety over 52 weeks from a phase-3, randomized, placebo-controlled trial

Abstract

Background: Few clinical trials have evaluated long-term treatment of nail psoriasis with biologics.

Objective: Safety and efficacy of adalimumab [ADA; Humira AbbVie Inc, North Chicago, IL, USA)] long-term treatment (52 weeks) was evaluated in a phase-3, randomized trial in patients with moderate-to-severe plaque psoriasis and concomitant moderate-to-severe fingernail psoriasis. Results from the first 26 weeks (Period A) have been reported.

Methods: Patients receiving 40 mg ADA every other week or placebo in Period A, continued with or switched to 40 mg ADA every-other-week treatment in the subsequent 26-week open-label extension (OLE) period. Main efficacy evaluations were ≥75% improvement in total-fingernail modified Nail Psoriasis Severity Index (mNAPSI 75) and achievement of Physician's Global Assessment for Fingernail Psoriasis of clear or minimal disease (PGA-F 0/1) with a ≥2-grade improvement from baseline, across the trial for patients who continued ADA from Period A through the OLE (Continuous-ADA Population). Safety was evaluated during the OLE and for patients receiving ADA at any time during the study (All-ADA Population).

Results: Of the 217 patients initially randomized in Period A, 188 (86.6%; 94 in each treatment group) entered the OLE after completion of or early escape from Period A. For the Continuous-ADA Population (N = 109), endpoint achievement rates improved from OLE entry (Week 26) to Week 52, including total-fingernail mNAPSI 75 (47.4-54.5%); PGA-F 0/1 (51.1-55.6%) and total-fingernail mNAPSI = 0 (6.6-17.9%). Serious adverse event and serious infection rates for the All-ADA Population (N = 203) were 6.9% and 3.4%, respectively.

Conclusions: In this population of psoriasis patients with concomitant, moderate-to-severe nail psoriasis, long-term efficacy and improvement in signs and symptoms of nail disease were demonstrated after every-other-week ADA treatment, including incremental improvements in rate of total clearance of nail disease. No new safety risks were identified for patients receiving at least one ADA dose across 52 weeks.

Figure 1

Patient Disposition in the OLE. For those patients who discontinued from study participation for more than one reason, only the primary reason is listed. Abbreviations: ADA, adalimumab; OLE, open‐label extension; pbo, placebo.

Figure 2

Main Efficacy outcomes over 52 weeks. (a) Achievement of Total‐Fingernail mNAPSI 75 (Continuous‐ADA Population). (b) Achievement of PGA‐F 0/1 with ≥2 Grades Improvement from BL (Continuous‐ADA Population). (c) Achievement of Total‐Fingernail mNAPSI 75 (OLE). (d) Achievement of PGA‐F 0/1 with ≥2 Grades Improvement from BL (OLE). Missing data were handled by multiple imputation. Abbreviations: ADA, adalimumab; BL, baseline; mNAPSI, modified Nail Psoriasis Severity Index; NRI, non‐responder imputation; OLE, open‐label extension; pbo, placebo; PGA‐F, Physician's Global Assessment of Fingernail Psoriasis; W, week.

Figure 3

Patient‐reported outcomes over 52 weeks. (a) Nail Psoriasis Pain (NRS) Improvement. (b) NPPFS Score Improvement. (c) Nail Ps QoL Improvement. (d) NAPPA QoL Improvement. Results are reported as mean improvement from baseline. Missing data were handled by multiple imputation. NAPPA, Nail Assessment of Psoriasis and Psoriatic Arthritis; NPPFS, Nail Psoriasis Physical Functioning Severity; NRS, Numeric Rating Scale; OLE, open‐label extension; Ps, psoriasis; QoL, quality of life.

Figure 4

Efficacy and patient‐reported outcomes by history of psoriatic arthritis, OLE. (a) Achievement of Total‐Fingernail mNAPSI 75. (b) Achievement of PGA‐F 0/1 with ≥2 Grades Improvement from BL. (c) Mean Improvement from BL in Nail Ps Pain (NRS). (d) Mean Improvement from BL in NPPFS score. (e) Mean Improvement from BL in Nail Ps QoL. (f) Mean Improvement from BL in NAPPA QoL. Missing data were handled by NRI for mNAPSI 75 and PGA‐F 0/1 and by LOCF for Nail Psoriasis Pain NRS, NPPFS, Nail Ps QoL and NAPPA QoL; LOCF data include standard error. Range of scores for Nail Ps Pain NRS, NPPFS and Nail Ps QoL scores are 0–10, and for NAPPA QoL, 0–4. ADA, adalimumab; DLQI, Dermatology Life Quality Index; LOCF, last observation carried forward; mNAPSI, modified Nail Psoriasis Severity Index; NAPPA, Nail Assessment of Psoriasis and Psoriatic Arthritis; NPPFS, Nail Psoriasis Physical Functioning Severity; NRI, non‐responder imputation; NRS, Numeric Rating Scale; OLE, open‐label extension; pbo, placebo; PGA‐F, Physician's Global Assessment of Psoriasis of the Fingernail; Ps, psoriasis; PsA, psoriatic arthritis; QoL, quality of life; W, week.