In 2005, the multicenter, double-blind, placebo-controlled EXPRESS trial studied 378 patients with moderate to severe psoriasis.20,21 In that trial, patients treated with infliximab showed a significant improvement in mean NAPSI from week 10 onwards, with reductions as high as 57.2% at week 24. Moreover, the patients in whom skin lesions responded very well to treatment (a reduction in PASI >90%) showed a mean improvement of 80.3% in NAPSI at week 50.20 A retrospective analysis of the EXPRESS trial reported a mean improvement in NAPSI of 28.3% at week 10, 61.4% at week 24, and 67.8% at week 50.21

In 2 Japanese Phase III clinical trials involving a total of 90 patients, significant improvement was observed in nail psoriasis in the patients treated with infliximab.22

In a recently published prospective study, Saraceno et al.23 compared the efficacy of tumor necrosis factor (TNF) antagonists in nail psoriasis.23 In total, 60 patients were enrolled in 3 treatment groups (adalimumab, etanercept, and infliximab) and studied for 24 weeks. At week 14, efficacy (assessed as a reduction in NAPSI) was higher in the infliximab group compared to the other 2 agents. At week 24, all 3 drugs achieved a similar reduction in mean NAPSI.

In an uncontrolled open-label prospective study, Rigopoulos et al.25 evaluated the efficacy of infliximab in 18 patients with psoriasis and nail involvement. Significant improvement in nail disease was observed in most of the patients at week 14, with a reduction in mean NAPSI from a baseline of 55.8 to 29.8. After 6 months of treatment, the mean NAPSI had declined to 3.3.

Table 1 shows the results of other studies in the literature involving patients with nail psoriasis who were treated with infliximab and other biologic agents.

Some authors consider that a specific profile of candidates for treatment with infliximab could be proposed because of the characteristics of this agent.28 The profile would include patients with severe plaque psoriasis associated with severe nail involvement and/or PsA.

The authors of the CRYSTEL study evaluated the effect of treatment with etanercept on patients with moderate to severe psoriasis and determined the prevalence of nail and joint symptoms and their impact on the patients’ quality of life.29 Of the 711 patients evaluated, who were randomized to receive either continuous (352) or paused (359) etanercept therapy for 54 weeks, 79% had nail psoriasis at the start of the study. Patients with nail psoriasis showed significant improvement at the end of the study, as evidenced by a 51% reduction in mean NAPSI.

In a recent randomized clinical trial (the NAIL study), Ortonne et al.30 analyzed the efficacy and safety of etanercept in the treatment of nail psoriasis in patients with moderate to severe psoriasis. The study included patients with nail psoriasis who had previously failed to respond to treatment with at least 1 systemic drug. Patients were randomized to receive either etanercept 50 mg twice weekly for 12 weeks followed by 50 mg weekly for 12 weeks or etanercept 50 mg for 24 weeks. At week 24, the authors observed a significant correlation between NAPSI and PASI scores and a significant decrease in the NAPSI score for the target fingernail, similar in both groups.

A prospective, multicenter, observational study was carried out in several Dutch hospitals to evaluate the effectiveness of TNF blockers in the treatment of juvenile PsA.32 The study included 18 patients. Nail pitting was observed in 39% of the patients at baseline. Seventeen patients were treated with etanercept and 1 with adalimumab. In most of the patients, the authors reported a good response in the case of psoriatic joint symptoms but not for skin and nail disease; 4 patients even developed de novo psoriasis during treatment.

The authors of a post hoc analysis of Phase IIIb of the BELIEVE clinical trial investigated the effect of PsA on the efficacy of adalimumab and the response to treatment of other markers of psoriasis burden, such as skin lesions, nail involvement, pain, pruritus, and quality of life.35 In that study, treatment with adalimumab resulted in considerable clinical improvement in skin and nail disease.

The REACH randomized controlled trial included 72 patients.36 Of the 31 patients who had nail psoriasis, a 50% reduction in NAPSI (NAPSI 50) was achieved in a higher percentage of the adalimumab-treated patients (56.5%) than the controls (12.5%) at week 16.

An uncontrolled, prospective study conducted in 2010 of 442 patients with PsA assessed treatment with adalimumab 40 mg administered subcutaneously every other week for 12 weeks.37 The mean NAPSI of the 164 patients with severe PsA and nail psoriasis was reduced by 57% at 12 weeks.

In recent years, several studies have reported that the prevalence of onychomycosis is greater in patients with nail psoriasis than in the healthy population, with rates ranging from 4.6% to 47.9%.18,41 Both dermatophyte and non-dermatophyte yeasts have been isolated.11,18,41 Al-Mutairi et al.42 studied the rate of onychomycosis in patients with nail psoriasis randomized to receive biologic therapy with etanercept, infliximab, or adalimumab for 24 weeks. In total 315 patients were studied and the results were compared with controls. Onychomycosis in association with nail psoriasis was more frequent in men and in patients treated with infliximab (33%). The prevalences for the other groups were 15.45% for etanercept, 13.33% for adalimumab, and 13.89% for the controls.

It has also been reported that patients being treated with TNF-α inhibitors for diseases other than psoriasis have developed psoriasis, nail psoriasis, and/or palmoplantar pustular psoriasis, and sometimes all 3 conditions. In a series of 120 patients, all 3 TNF-α inhibitors available on the market triggered this type of cutaneous lesions: infliximab (n = 63), etanercept (n = 37), and adalimumab (n = 26).43 Psoriasis was the most common (n = 73), followed by palmoplantar pustular psoriasis (n = 37), and nail psoriasis (n = 6). In 75 patients, the induced psoriasis was de novo, while in 24 the reaction was an exacerbation or aggravation of preexisting psoriatic disease.

In a subanalysis of the results of 3 double-blind, randomized trials in which infliximab was used to treat moderate to severe psoriasis, Menter et al.54 examined its effectiveness in different areas of the body. A total of 1462 patients had been included in these 3 trials (EXPRESS, EXPRESS II, and SPIRIT). Following treatment with infliximab for 10 weeks, an improvement in PASI response similar to the overall value was observed for all 4 sites studied (head-neck, upper limbs, trunk, and lower limbs). At 10 weeks, the percentage of patients with at least a PASI 75 response or at least a PASI 90 response in the infliximab group vs placebo was as follows: 85.5% vs 22% (≥ 75%) and 68.9% vs 12% (≥ 90%) in the SPIRIT trial; 84.8% vs 12.5% (≥ 75%) and 73.1% vs 8.3% (≥ 90%) in the EXPRESS study; and 79% vs 10% (≥ 75%) and 66.6% vs 5.5% (≥ 90%) in the EXPRESS II trial.

The authors of an open-label, randomized study that compared the efficacy and safety of continuous (n = 1272) vs interrupted (n = 1274) treatment with etanercept reported a 58% reduction in PGA for scalp psoriasis at 12 weeks in both groups.55 At week 24, the efficacy observed in scalp psoriasis was greater in the continuous treatment group.

In a randomized, double-blind, placebo-controlled trial, Bagel et al.53 evaluated the efficacy of etanercept in patients with moderate to severe psoriasis and scalp involvement. At 12 weeks, etanercept 50 mg administered twice weekly achieved an 87% reduction in PSSI, as compared to a 20% reduction in the placebo group. Continued treatment with etanercept 50 mg once a week maintained the response in scalp psoriasis through week 24.

In a randomized, double-blind, placebo-controlled study, Tyring et al.56 assessed patients with psoriasis and scalp involvement receiving treatment with etanercept using patient-reported outcomes relating to pruritus, pain, health-related quality of life, depression, emotional stress, and patient satisfaction with treatment. At 12 weeks, they observed a significant difference between the outcomes reported by the patients treated with etanercept and the controls.

The multicenter BELIEVE randomized clinical trial assessed the efficacy of combining therapy with adalimumab—at the dosage specified in the SPC—and topical treatment (calcipotriol 50 μg/g plus betamethasone 0.5 mg/g) in patients with moderate to severe psoriasis who had previously had an inadequate response to systemic therapies.35 Although the study protocol did not call for the application of topical treatment on the scalp or nails, the PSSI and NAPSI were used to assess the response to adalimumab at weeks 0, 8, and 16. In total, 663 of the 730 patients in the study (91.3%) had scalp psoriasis (PSSI > 0). After 16 weeks of treatment the mean reduction in PSSI score was 77.2%.

The authors of a prospective observational study in Japan that compared the therapeutic efficacy of adalimumab and infliximab in the treatment of psoriasis vulgaris also assessed the impact of both drugs on scalp involvement.57 They studied 21 patients, some of whom were on concomitant topical treatment with vitamin D analogues. Patients were treated with infliximab or adalimumab, according to their preference. At week 16, the authors observed a significantly lower PSSI response rate in the group receiving adalimumab (54.5%) compared to the infliximab-treated group (90%).

In a retrospective study, Sola et al reported significant improvement in scalp psoriasis at 24 weeks following treatment with adalimumab at the dosage regimen specified in the SPC.39

A multicenter randomized controlled trial assessed the efficacy and safety of treatment with infliximab in 24 patients with nonpustular palmoplantar psoriasis.63 At week 14, significant improvement was observed in the treatment group (50% reduction in the mean surface area of the affected palms and soles as compared to an increase of 15% in the group receiving placebo). However, the study did not achieve its primary endpoint since at week 14 only 33% of patients had achieved a 75% reduction on the modified PPPASI used. The authors attributed these results to the small size of the sample and the fact that the patients included had very low baseline scores.

Table 2 shows the results of other studies and case reports in the literature in which palmoplantar psoriasis was treated with infliximab or other biologic agents.

In a randomized controlled trial, Bissonnette et al.67 analyzed the efficacy of etanercept in the treatment of palmoplantar pustulosis. Fifteen patients were randomized (2:1) to receive either etanercept 50 mg or placebo twice weekly for 3 months, and then all the patients in the study were treated with etanercept 50 mg twice weekly for a further 3 months. At 24 weeks, a statistically significant reduction was observed in the PPPASI in the patients treated with etanercept throughout the whole study but not in the crossover group (P = .038, n = 10).

The chief objective of the randomized controlled REACH trial was to assess the efficacy of adalimumab in the treatment of palmoplantar psoriasis.36 The study enrolled 72 patients, who were randomized (2:1) to receive either adalimumab (49) or placebo (23). The authors found that in the group of patients treated with adalimumab those who achieved at least a NAPSI 50 response also improved their score on the PGA scale relating to clearing of hands and/or feet.

An open-label study by Richetta et al.69 included 11 patients treated with adalimumab 40 mg administered subcutaneously every other week. Of these, 54% (6/11) improved by at least 1 point on the PGA scale, and 8 of them also showed significant improvement on the DLQI scale at week 12.