Current systemic treatments for nail psoriasis

Nail psoriasis is a common manifestation in patients with psoriasis and psoriatic arthritis (PsA), affecting up to 60% of patients with psoriasis and ~80% of patients with PsA.¹ Nail psoriasis is associated with lower quality of life in patients with psoriatic disease, and can be predictive of PsA development.¹ The understanding of nail psoriasis is limited, due to a lack of clinical trials focused on this manifestation.² Therefore, available treatment data of nail psoriasis have been generated from clinical trials investigating psoriasis and PsA. Here, we present the currently available systemic treatments for nail psoriasis.

Pathogenesis¹

In nail psoriasis, inflammation of the nail bed or matrix occurs, resulting in morphological changes. Nail psoriasis is also associated with enthesitis, which can be an early indicator of PsA and can suggest increased disease severity. In nail psoriasis, the nail bed can become discolored, with salmon patches, splinter hemorrhages, and onycholysis also occurring. The nail matrix can become pitted, with leukonychia, Beau lines, and nail crumbling.

Diagnosis¹

Nail psoriasis is diagnosed by the presence of psoriatic changes in the nail. In patients with psoriatic disease, nail manifestations should be monitored continuously, as they can be a predictor of disease evolution. In the clinical trial setting, the Nail Psoriasis Severity Index (NAPSI) is used as a tool to assess nail psoriasis. With the NAPSI, each nail is divided into quadrants and scored for presence or absence of psoriatic changes (1 for presence and 0 for absence), with the scores added together to obtain a total NAPSI score, as shown in Figure 1. A modified NAPSI (mNAPSI) can also be used, which measures disease severity in each nail, but this can be difficult to carry out in a real-world setting. Physician’s Global Assessment of Fingernail Psoriasis (PGA-F) can also be used to assess nail psoriasis, with a PGA-F score ≥3 indicating moderate-to-severe nail psoriasis.

NAPSI, Nail Psoriasis Severity Index.
*Data from Kirkham, et al.¹ Created with Biorender.com

Treatments²

There are multiple treatments available for patients with nail psoriasis. Treatment are selected based on disease severity, comorbidities, and extent of skin and joint involvement. Topical and injectable therapies are usually used in patients where only a few nails are involved, with systemic therapies used when nail psoriasis is severe. Table 1, Table 2, and Table 3 provide an overview of tumor necrosis factor alpha inhibitors,^2,3,4,5 interleukin inhibitors, and other systemic therapies currently being used or investigated for nail psoriasis.

Table 1. TNF-a inhibitors used for the treatment of nail psoriasis*

mNAPSI, Modified Nail Psoriasis Severity Index; NAPSI, Nail Psoriasis Severity Index; NP, nail psoriasis; PsA, psoriatic arthritis; PsO, psoriasis; SC, subcutaneous; TNF-a, tumor necrosis factor alpha. *Adapted from Battista, et al.2 and Drugs.com3,4
Therapy2	FDA Approved?3,4	Efficacy2
Etanercept	PsO and PsA	Showed efficacy in treating NP in multiple clinical trials.
Infliximab	PsO and PsA	Shown to significantly improve nail involvement in patients with psoriasis in the phase III EXPRESS trial (NCT00106834).
Adalimumab	PsO and PsA	Well tolerated, with improvements to NAPSI score observed in a phase III study.
Certolizumab	PsO and PsA	SC administration showed efficacy in a real-life multicenter study.
Golimumab	PsA, rheumatoid arthritis, ankylosing spondylitis	Improvements in mNAPSI score observed in treating NP associated with PsA.

Table 2. IL inhibitors used for the treatment of nail psoriasis*

F-PGA, Physician Global Assessment of Fingernail Psoriasis; NAPSI, Nail Psoriasis Severity Index; NP, nail psoriasis; PsA, psoriatic arthritis; PsO, psoriasis; RCT, randomized controlled trial. *Adapted from Battista, et al.2 and Drugs.com3,4
Therapy2	FDA Approved?3,4	Efficacy2
Ustekinumab	PsO and PsA	Showed improvements in NAPSI score in both finger and toenail psoriasis; however, some trials suggest more marked improvements in the nails of the big and 2nd toes.
Ixekizumab	PsO and PsA	Showed efficacy in treating NP and greater complete nail clearance when compared with etanercept in UNCOVER-2 and -3 (NCT01597245; NCT01646177)
Secukinumab	PsO and PsA	Showed sustained efficacy in treating NP for up to 2.5 years in the TRANSFIGURE trial (NCT01807520)
Brodalumab	PsO	Brodalumab showed an improved mean NAPSI score over ustekinumab in the AMAGINE-2 and -3 trials.
Bimekizumab		Showed better efficacy compared to placebo in the BE COMPLETE (NCT03896581) clinical trial at 16 weeks.
Guselkumab	PsO and PsA	Positive NAPSI score and F-PGA responses at Week 16 in VOYAGE 1 and 2 (NCT02207231; NCT02207244)
Risankizumab	PsO and PsA	In the KEEPsAKE1 (NCT03675308) trial, risankizumab treatment led to significant improvements in nail outcomes versus placebo in patients with NP.
Tildrakizumab	PsO	No RCTs evaluating efficacy in nail disease. Some real-life experiences suggest it can improve NAPSI scores.

Table 3. Other therapies used for the treatment of nail psoriasis*

NAPSI, Nail Psoriasis Severity Index; NP, nail psoriasis; PsA, psoriatic arthritis; PsO, psoriasis; TNF-a, tumor necrosis factor alpha; UVA, ultraviolet A; UVB, ultraviolet B. *Adapted from Battista, et al.2, Drugs.com3,4, and the National Psoriasis Foundation.5
Therapy2	FDA Approved?3,4,5	Efficacy2
Acitretin	PsO	Case studies suggest it can improve NP, but another study reported worsening of NP after acitretin.
Methotrexate	PsO	In the METOP trial (NCT02902861), NP improved in some patients, although the improvement was slow.
Cyclosporine	PsO	Studies show that cyclosporine has efficacy in treating NP; however, improvements may be greater when combined with a TNF-a inhibitor.
Dimethylfumarate	PsO	Led to improvements in NP from baseline in the SKILL study.
Phototherapy/ photochemotherapy	PsO	Studies have shown the nail plate completely blocks UVB radiation, and mostly blocks UVA, so phototherapy has low efficacy in NP.
Apremilast	PsO and PsA	Apremilast improved NAPSI scores in NP in the ESTEEM 1 and 2 trials (NCT01194219; NCT01232283) from baseline to 16 weeks.

Conclusion 

Nail involvement in patients with psoriasis can be predictive of the severity of disease, and can lead to lower quality of life.¹ Therefore, prompt treatment for nail psoriasis is important.¹ There are multiple systemic treatments available which have shown efficacy in treating nail psoriasis, and treatment should be chosen based on patient characteristics, disease severity, joint involvement, and available guidelines.² Additional studies, to compare efficacy and safety of treatments in nail psoriasis specifically, will improve knowledge and treatment options for these patients.