Alefacept in the treatment of psoriatic nail disease: a proof of concept study

Abstract

Nail psoriasis can be debilitating and as therapeutic options are limited, it can be notoriously difficult to treat. As there are many novel medications currently undergoing clinical trials in psoriasis, questions have arisen concerning the effectiveness of these novel therapies with regard to psoriatic nail disease. We at hand the results of a prospective, open-label, essay of concept study to determine the efficacy and safety of alefacept in subdues with moderate to severe nail psoriasis.

Introduction

Nail psoriasis affects up to 50% of psoriasis patients and can have a strict impact on the patient's quality of life. (1) Psoriatic nail changes can manifest as nail matrix disease (pitting, leukonychia, r speckles in the lunula, and nail plate crumbling/distortion) and nail bed disease (salmon patch, onycholysis, hyperkeratosis, and splinter hemorrhage). Topical therapies, similar as corticosteroids, calcipotriol, retinoids, and 5-fluorouracil, have limited efficacy and are not without side issues Traditional systemic therapies such as methotrexate, cyclosporine, acitretin, and PUVA can also have concomitant tolerability and toxicity relate tos Recent reports have demonstrated the utility of biologic agents in the management of this notoriously difficult to treat disease. (23) Alefacept is a fusion protein that combines human IgG1 and LFA-3 and has been FDA approved for the treatment of moderate to cruel chronic plaque psoriasis in adults. As nail psoriasis can posture a clinical therapeutic dilemma, we designed a prospective open-label trial of concept study to determine the efficacy and safety of alefacept in bring under rules with moderate to severe nail psoriasis.

inquiry Design and Methods

After obtaining local Institutional Review Board approval and written informed approval from each patient, we listed 15 subjects between the ages of 25 and 64 Patients with moderate to rigid nail psoriasis and candidates for systemic therapy for cutaneous plaque psoriasis were eligible. Fungal agriculture and KOH were obtained and were negative prior to ingress In addition, CD4 counts were drawn at baseline and each 2 weeks thereafter, and doses were held if the CD4 enumerate dropped below 250 cells/[mm.sup.3]. make submissives were excluded from any topical treatment to the nails within the previous 28 days, any systemic treatment for psoriasis within the past month or any biologic therapy within the previous 3 month controls received alefacept, 15 mg IM, each week for 12 weeks, followed by dint of a 12-week observation period. Assessments and photographs of the target nail were taken at baseline and at week 24 (Figure 1)

[FIGURE 1 OMITTED]

To assess nail psoriasis, we used a modification of the nail psoriasis severity index (NAPSI) for the target nail as previously reported. (45) Briefly, the target nail is divided into quadrants, and each quadrant is given a score of 0 to 3 for none, mild, moderate, or strait-laced for each parameter of nail matrix or bed disease. For pitting, mild disease was defined as 1 to 3 pits for quadrant, moderate disease was defined as 4 to 9 pits through quadrant, and severe disease as 10 or more pits by quadrant. For the remaining parameters (ie, leukonychia, onycholysis, salmon patch, etc) mild disease was defined as involvement of one-third or les of each quadrant, moderate was defined as involvement of between one-third and two-thirds of each quadrant, and censorious as involvement of greater than two-thirds of each quadrant. The highest possible score is 96 derived from 4 (quadrants) times 8 (parameters) times 3 (severe disease). We have feeling that this system has the sensitivity to capture clinically significant change. As the tendency of the study encompassed psoriatic nail disease, formal assessment of skin severity and improvement (PASI scoring) was not done.

Results

Fifteen subdues were enrolled, and all complet the 12-week treatment phase and the 24-week follow-up During the treatment phase, single subject had a CD4 enumerate fall below 250 cells/[mm.sup.3]; treatment was resum in this subdue after normalization of CD4 enumerate with no further interruption of treatment. There was individual unrelated serious adverse event.

Target NAPSI scores were bring togethered at baseline and week 24 for each make submissive The t-test was used to assess whether the difference or percentage difference was significantly different from nothing At baseline, modified target NAPSI scores ranged from 8 to 41 with a mean of 19 (+/- 87) (Table 1) At week 24 the modified target NAPSI had decreased to a range of 2 to 25 with a mean of 11 (+/- 62 p=0003) This exhibits a mean percent reduction from baseline of 39% (+/- 298 p=0002)

The event of alefacept on the combined subcomponent scores for nail matrix and bed disease was also assessed. For nail matrix disease (pitting, leukonychia, r specks in the lunula, and nail plate crumbling/distortion), the mean and percent score reductions were statistically significant with values of 62 (+/- 51 p=00003) and 53% (+/- 325 p[les than or equal to].0001), respectively. For nail bed disease (salmon patch, onycholysis, hyperkeratosis, and splinter hemorrhage), the mean and percent score reductions were not statistically significant with values of 21 (+/- 39 p=0539) and 20% (+/- 433 p=0952) respectively.