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- Materials and methods
Plaque psoriasis is a chronic, recurring condition that varies in severity and body surface area (BSA) affected. It can manifest from few localized areas to complete body coverage, and can also primarily involve the hands and feet, including nails. Of the 1–3% of the general population who have psoriasis, an estimated 3–41% have chronic plaque psoriasis of the hands and/or feet, and approximately 50% of psoriasis patients have nail involvement. Despite the relatively small BSA that is affected by psoriasis of the hands and/or feet, quality of life for these patients can be disproportionally poor due to pain, discomfort, and limitations in performing activities of daily living.[1, 3-7] Nail psoriasis can alter the sense of touch and reduce manual dexterity. Psoriasis of the hands and/or feet can also cause embarrassment due to the unsightly appearance of scales and fissures on the skin, and pitting, discoloration and crumbling of the nail.
Published information related to specific treatment of hand and/or foot psoriasis focuses mainly on palmoplantar psoriasis. Although topical therapies, including corticosteroids, retinoids, calcipotriol, salicylic acid, and coal tar, are widely used, palmoplantar psoriasis is often resistant, and prolonged corticosteroid use can have undesirable side-effects.[9-11] Common light therapies, including topical psoralen plus long-wave ultraviolet A (PUVA), broadband ultraviolet B, and narrowband ultraviolet B (NB-UVB), have also been used, but published, definitive conclusions about the effectiveness of NB-UVB on localized psoriasis are lacking. In addition, the multiple clinic visits for treatment can be inconvenient.
Established systemic therapies are typically employed when the disease is severe or refractory to topical treatment. These include PUVA with oral psoralen, methotrexate, cyclosporine, and retinoids; however, adverse effects can limit long-term use in patients with psoriasis of the hands and/or feet. Patients with localized psoriasis may need multiple treatment agents, which include a combination of topical and systemic medications, during the course of disease to achieve treatment benefit.[9, 10] Biologics approved for the treatment of chronic plaque psoriasis have also been used successfully to treat hand and/or foot psoriasis, although none are currently approved specifically for this condition, and most of the evidence is limited to small clinical studies and case reports.[13-22]
Adalimumab, a fully human monoclonal antibody that neutralizes tumour necrosis factor (TNF) and modulates TNF-related biological responses, is approved in the United States and Europe for multiple indications, including psoriatic arthritis (PsA) and moderate-to-severe chronic plaque psoriasis.[23, 24] Recently, REACH (ClinicalTrials.gov NCT00735787), a phase 4, 16 week, multicenter, randomized, double-blind, placebo-controlled trial with an additional 12-week open-label period, demonstrated that adalimumab was efficacious and well-tolerated for the treatment of psoriasis of the hands and/or feet for up to 28 weeks. Following adalimumab treatment, significant improvements were seen in scores evaluating efficacy and pain. These included erythema, scaling, induration, and fissuring (ESIF); Nail Psoriasis Severity Index (NAPSI); and plaque psoriasis and PsA pain Visual Analogue Scale (VAS) scores.
This post hoc analysis REACH evaluated the effects of baseline demographic and disease characteristics on the efficacy of adalimumab compared with placebo for the treatment of chronic plaque psoriasis of the hands and/or feet during the 16-week double-blind period.
- Top of page
- Materials and methods
This post hoc analysis of the REACH 16-week period demonstrated that overall, patient baseline demographic and disease characteristics did not affect the efficacy of adalimumab for the treatment of chronic plaque psoriasis of the hands and/or feet. Adalimumab showed greater efficacy compared with placebo for the primary efficacy measure (hfPGA score of clear or almost clear), regardless of age, gender, weight, PASI score, disease duration, PsA history, prior systemic treatment, smoking history, or nail disease. This is the first analysis of the impact of baseline patient demographic and disease characteristics on the efficacy of a TNF-antagonist for hand and/or foot psoriasis in a double-blind, controlled trial. The clinical responses observed with adalimumab treatment are consistent with the overall results of the placebo-controlled period of REACH and with adalimumab data for the treatment of psoriasis elsewhere on the body. Adalimumab also was efficacious in treating nail disease in patients with hand and/or foot psoriasis; marked improvement in nail disease correlated with significant improvements in skin disease and patient-reported outcomes.
All patients demonstrated improved responses following adalimumab treatment, but greater response was seen in patients of younger age (<65 years), lighter bodyweight (<88 kg), with higher PASI scores (≥10), longer disease duration (≥4.7 years), history of PsA, prior systemic treatment, and nail involvement. Such response differences may be due to the small number of patients included in this analysis. Higher response rates have been reported in younger compared with older (<65 vs. ≥65 years of age) adalimumab-treated patients with moderate-to-severe psoriasis not limited to hands and/or feet. Also, higher response rates in patients of lower weight have been reported in the treatment of psoriasis elsewhere in the body with adalimumab and with other fixed-dose systemic biologics such as alefacept and etanercept. While a higher response rate was noted in patients with PASI score ≥10, this finding does not necessarily indicate that patients with more severe disease responded better to adalimumab compared with those of less-severe disease; this is based on limitations of the PASI scoring method (compounded weighted averaging of all components), which can hide potential response differences. Patients with longer disease duration characteristically do not respond as well to systemic treatment as those with shorter disease duration. The results of this post hoc analysis, however, suggest that adalimumab is efficacious even in patients with well-established psoriasis of the hands and/or feet. Patients who had received prior systemic therapy also had a better response to adalimumab than patients with no prior systemic treatment, suggesting that patients had not become refractory to adalimumab treatment despite failing other systemic agents, including biologics. In patients with psoriasis, there is an increased prevalence of smoking, which is a known risk factor for incident psoriasis. The response to adalimumab treatment in this analysis did not appear to be affected by patient smoking status, although the small number of patients does not allow a comparison to the general psoriasis population.
Nail involvement can contribute significantly to the burden of illness in patients with hand and/or foot psoriasis. In this study, nail psoriasis at baseline was identified for about half of all patients, which is similar to reports of nail involvement in patient populations with all types of psoriasis, including plaque psoriasis (35–50%). A marked improvement in nail disease after 16 weeks of adalimumab treatment was associated with marked improvements in both skin disease (hfPGA) and in patient-reported outcomes (ESIF, DLQI, pain VAS scores). Several other studies of biologic agents, including TNF inhibitors, for treatment of patients specifically with nail psoriasis have shown concomitant improvements in nail response and psoriatic skin and/or quality of life.[29-31] While NAPSI responses reported in this analysis are only through week 16, further improvements in nail psoriasis and quality of life with longer duration of adalimumab therapy have been reported.[25, 32, 33] Improvement in nail psoriasis has also been correlated with improvement in moderate-to-severe psoriasis elsewhere in the body following treatment with infliximab, etanercept and adalimumab, and with ustekinumab. Small studies comparing the efficacy of anti-TNF agents in nail psoriasis show that patients treated with infliximab experience greater NAPSI improvement early in therapy compared with etanercept and adalimumab, although the differences among these biologics become less pronounced after 48 weeks of therapy.[30, 36]
Few large, prospective randomized studies have been published about the effect of biologic agents on psoriasis of the hands and/or feet. Studies of systemic treatment for hand and/or foot psoriasis are often accomplished as subanalyses of studies in psoriasis generally affecting the entire body and can exclude patients with psoriasis that manifests only on the hands and/or feet when inclusion criteria limits psoriasis involvement to ≥10% of BSA. REACH is one of the first randomized, placebo-controlled trials that focused specifically on chronic plaque psoriasis of the hands and/or feet. Other biologics, including etanercept, infliximab,[14, 15] ustekinumab,[16, 17] alefacept,[18-20] and efalizumab[21, 22] (withdrawn from approval due to safety issues) have demonstrated clinical improvement in patients with psoriasis of the hands and/or feet, although the majority of these studies were case studies showing no statistically significant improvements. In a randomized, double-blind, placebo-controlled trial of patients with non-pustular palmoplantar psoriasis, an improved response with infliximab was observed compared with placebo, although the study did not meet its primary efficacy endpoint.
The hfPGA scale used in this study to measure psoriasis severity, employed a 5-point scale (0 = clear; 4 = severe) to evaluate psoriatic lesions on all surfaces of the hand and foot. Despite being a subjective scale, the consistent efficacy observed among adalimumab-treated patients through various secondary endpoints in REACH support the primary endpoint (hfPGA of clear or almost clear) result. In addition, the use of this scale resulted in a more comprehensive assessment of localized psoriasis on the hands and feet, compared with other studies that mostly used the palmoplantar pustular PASI (PPPASI) score,[37, 38] or modification thereof. The PPPASI score evaluates only the palmar and plantar aspects of the hands and/or feet, and includes a score for pustules, which replaces the regular PASI score of induration. In a recent clinical trial, a measure similar to the hfPGA was used, but only for palmar and/or plantar evaluation based on a 5-point scale (0 = clear, 5 = most severe).
This study is limited by the small number of patients included in the analyses. As a result, statistical comparisons of responses could not be made between adalimumab and placebo-treatment subgroups for the primary endpoint, or between NAPSI 50 Responders and Non-Responders for improvements in patient-reported outcomes among patients with psoriatic nail involvement at baseline. In addition, patients with pustular psoriasis were excluded from the trial, which limits generalization of the results of this analysis to non-pustular forms of hand and/or foot psoriasis. Finally, the analyses were conducted within a relatively short period of 16 weeks during the double-blind controlled period of the trial.