Abstract: We included 18 studies involving 1266 participants. We were not able to pool due to the heterogeneity of many of the studies. Our primary outcomes were 'Global improvement of nail psoriasis as rated by a clinician', 'Improvement of nail psoriasis scores (NAS, NAPSI)', 'Improvement of nail psoriasis in the participant's opinion'. Our secondary outcomes were 'Adverse effects (and serious adverse effects)'; 'Effects on quality of life'; and 'Improvement in nail features, pain score, nail thickness, thickness of subungual hyperkeratosis, number of affected nails, and nail growth'. We assessed short-term (3 to 6 months), medium-term (6 to 12 months), and long-term (> 12 months) treatments separately if possible. Two systemic biologic studies and three radiotherapy studies reported significant results for our first two primary outcomes. Infliximab 5 mg/kg showed 57.2% nail score improvement versus -4.1% for placebo (P < 0.001); golimumab 50 mg and 100 mg showed 33% and 54% improvement, respectively, versus 0% for placebo (P < 0.001), both after medium-term treatment. Infliximab and golimumab also showed significant results after short-term treatment. From the 3 radiotherapy studies, only the superficial radiotherapy (SRT) study showed 20% versus 0% nail score improvement (P = 0.03) after short-term treatment. Studies with ciclosporin, methotrexate, and ustekinumab were not significantly better than their respective comparators: etretinate, ciclosporin, and placebo. Nor were studies with topical interventions (5-fluorouracil 1% in Belanyx® lotion, tazarotene 0.1% cream, calcipotriol 50 ug/g, calcipotriol 0.005%) better than their respective comparators: Belanyx® lotion, clobetasol propionate, betamethasone dipropionate with salicylic acid, or betamethasone dipropionate. Of our secondary outcomes, not all included studies reported adverse events; those that did only reported mild adverse effects, and there were more in studies with systemic interventions. Only one study reported the effect on quality of life, and two studies reported nail improvement only per feature. Infliximab, golimumab, SRT, grenz rays, and electron beam caused significant nail improvement compared to the comparative treatment. Although the quality of trials was generally poor, this review may have some implications for clinical practice. Although powerful systemic treatments have been shown to be beneficial, they may have serious adverse effects. So they are not a realistic option for people troubled with nail psoriasis, unless the patient is prescribed these systemic treatments because of cutaneous psoriasis or psoriatic arthritis or the nail psoriasis is severe, refractory to other treatments, or has a major impact on the person's quality of life. Because of their design and timescale, RCTs generally do not pick up serious side-effects. This review reported only mild adverse effects, recorded mainly for systemic treatments. Radiotherapy for psoriasis is not used in common practice. The evidence for the use of topical treatments is inconclusive and of poor quality; however, this does not imply that they do not work. Future trials need to be rigorous in design, with adequate reporting. Trials should correctly describe the participants' characteristics and diagnostic features, use standard validated nail scores and participant-reported outcomes, be long enough to report efficacy and safety, and include details of effects on nail features.

Plain-language summary: Psoriasis is a common chronic skin disease with a prevalence in 2% to 3% of the population, according to European studies. Involvement of the nails occurs in about 50%. Nail psoriasis is difficult to treat, but may respond to some treatments. We aimed to review the efficacy and safety of the treatments used for nail psoriasis. We included 18 randomised controlled clinical trials (RCTs), which involved 1266 participants and were mostly based on a single study per treatment. Ten studies assessed topical treatments, i.e. applied to the surface of the skin (clobetasol, ciclosporin in maize oil, hyaluronic acid with chondroitin sulphates, 5-fluorouracil, a combination of dithranol with salicylic and UVB, tazarotene, and calcipotriol); 5 studies assessed systemic treatments, i.e. taken orally (golimumab, infliximab, ustekinumab, ciclosporin, and methotrexate); and 3 studies assessed radiotherapy (electron beam, grenz ray, and superficial radiotherapy). With regard to other treatments that are used for nail psoriasis, no RCTs had been carried out. It was not possible to pool and compare the results because the studies were all so different. In 5 studies, we found significant improvement of nail psoriasis compared to placebo: with infliximab (5 mg/kg), golimumab (50 mg and 100 mg), superficial radiotherapy, electron beam, and grenz rays. Although powerful systemic treatments have been shown to be beneficial, they may have serious adverse effects. So they are not a realistic option for people troubled with nail psoriasis, unless the patient is a candidate for these systemic treatments because of skin psoriasis or psoriatic arthritis. Because of their design and timescale, RCTs generally do not pick up serious side-effects. This review reported only mild adverse effects, recorded mainly for systemic treatments. Radiotherapy for psoriasis is not used in common practice. The evidence for the use of topical treatments is inconclusive and of poor quality; however, this does not imply that they do not work. Topical treatment options could be beneficial and need to be further investigated. Clinical trials on nail psoriasis need to be rigorous in design, with clear reporting to enable readers to better interpret the results. Trials should accurately describe the participants' characteristics and diagnostic features of nail psoriasis; use standard validated nail scores and patient-reported outcomes; be long enough to report efficacy and safety; and include more details of effects on nail features.