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Current systemic treatments for nail psoriasis

By Ella Dixon

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Oct 4, 2023

Learning objective: After reading this article, learners will be able to cite the latest data for treatments of nail psoriasis.


Test your knowledge! Take our quick quiz before and after you read this article to find out if you improved your knowledge. Results help us to improve content and continually provide open-access education.

Question 1 of 2

Treatment with which of the following interleukin inhibitors led to significant improvements in nail psoriasis outcomes compared with placebo in the KEEPsAKE1 trial?

A

B

C

D

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.

Figure 1. NAPSI score and common symptoms of 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.

References

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