Introduction: Psoriasis is a chronic inflammatory disease that may also involve nails. Unfortunately, topical treatments available are limited and often responsible for side effects and/or lack of compliance due to the necessary prolonged use to see results. Intralesional treatment instead is often unwanted or unaccepted by patients. Lack of efficacy is, moreover, always a possible outcome. Novel modalities for the therapy of nail psoriasis are thus needed and always welcomed. Case Presentation: We then aimed to develop a topical 2% tofacitinib formulation expected to facilitate nail penetration and use in patients with recalcitrant forms of nail psoriasis unwilling to accept other routes of administration of treatment besides the topical one. Conclusion: These preliminary data, despite the use in 3 patients only, suggest a potential use of topical tofacitinib 2% for nail psoriasis. Further studies on bigger groups are however necessary to confirm the present encouraging results and establish the effectiveness and safety also in more severe cases or in the pediatric population.

Established Facts

  • Nail psoriasis is notoriously difficult to treat.

  • Delivery of topical drugs might be difficult, mildly effective, and time consuming.

  • Clinicians are often reluctant to prescribe systemic treatments when the disease is limited to the nails.

Novel Insights

  • Studies suggest that topical tofacitinib is efficacious in treating the skin lesions due to psoriasis.

  • We aimed to develop a topical 2% tofacitinib formulation expected to facilitate nail penetration and use in patients with recalcitrant forms of nail psoriasis.

  • Tofacitinib 2% ointment has a potential role in the treatment of nail psoriasis.

Psoriasis is a chronic inflammatory disease that may also involve nails [1]. Nail psoriasis can affect more than 50% of patients with plaque psoriasis and up to 80% of patients with psoriatic arthritis [1]. Since hands are important for social life, nail psoriasis is detrimental for many patients and associated with emotional distress and a reduced quality of life [2, 3]. Unfortunately, nail psoriasis is often challenging to treat, especially when it presents in its isolated form [4]. Moreover, almost 20% of patients treated with systemic therapies whose skin and/or joint lesions are responsive may still have nail affected and require an additional topical or intralesional treatment as a booster or a maintenance treatment after systemic treatment withdrawal [4]. Unfortunately, topical treatments available, especially for nail matrix psoriasis, are limited and sometimes responsible of side effects or poor compliance due to the prolonged use necessary to see results. Intralesional treatment instead, despite being very effective, is often unwanted or unaccepted by patients. Lack of efficacy is, moreover, always a possible outcome of every topical or intralesional treatment. Novel modalities for the therapy for nail psoriasis are thus needed and always welcomed.

Tofacitinib is a Janus kinase (JAK) inhibitor effective in skin and joints psoriasis [5]. It blocks signaling of different inflammatory cytokines through inhibiting the JAK-STAT pathway. It appears to be effective in treating psoriasis through a direct effect on dysregulated keratinocytes, reduction of inflammatory infiltrations, and normalization of the interleukin-23/T-helper 17 axis [5]. When the disease is limited to the nails, however, there might be no need to prescribe an oral JAK inhibitor unless the treatment is extensively discussed with the patient – topical administration could also reduce the risk of adverse events in such a limited disease and should be preferred. Studies suggest that topical tofacitinib is efficacious in treating the skin lesions due to psoriasis [6‒8]. The effect on nail psoriasis was not however investigated. Since the fact that most topical formulations will likely not be suitable to treat nail lesions, given their limited penetration of the nail unit, we aimed with this study to develop a topical 2% tofacitinib formulation expected to facilitate nail penetration and use in patients with recalcitrant forms of nail psoriasis unwilling to accept other routes of administration of treatment besides the topical one.

As stated, we developed a topical 2% tofacitinib formulation expected to facilitate nail penetration. The ointment was compounded by Chemistry Rx Compounding and Specialty Pharmacy using FDA-compliant tofacitinib citrate bulk powder, dimethyl sulfoxide, and Aquaphor Healing Ointment.

The compounded medication was prepared under consideration of all current guidelines provided by the USA Pharmacopeia (USP) Chapter <795>, Pharmaceutical Compounding-Nonsterile Preparations, which also specifies the minimum stability of various compounded preparations. Tofacitinib ointment was compounded as an anhydrous formulation. Anhydrous compounds that are designated for topical use must be labeled with a beyond-use date of 6 months. This is the minimum time frame during which such a compound will be stable.

We then performed a split-hand (non-dominant hand) study with an application of 2% tofacitinib ointment (compassionate use) for 12 weeks in 3 patients aged 48, 45, and 36 years old. Baseline NAPSI on treated hand was 36, 35, and 20, respectively. In the non-treated hand (dominant hand) was instead 33, 24, and 12.

The ointment was applied once a day at bedtime, under occlusion (under a plastic wrap), in the periungual region and nail plate area. On the other hand, i.e., the dominant hand, patients did not apply anything – not even a hand moisturizer.

We enrolled stable patients (Psoriasis Area Severity Index (PASI) <3, Psoriasis Epidemiology Screening Tool negative, Nail Psoriasis Severity Index (NAPSI) >3 with nail psoriasis resistant to topical clobetasol, combination of betamethasone/calcipotriol and who refused intralesional steroid injections. Patients were not under any other concomitant treatment, and a wash out period of 2 years was reported after previously administered systemic treatments (acitretin and methotrexate).

After 12 weeks, treatment was stopped due to success and patients were followed up for further 12 weeks with no treatment. Patients achieved a total NAPSI of 5, 8, and 0 (Table 1) after 12 weeks of topical treatment and also maintained the remission during the 12 weeks of follow-up (Fig. 1). Two patients (number 2 and 3) showed a slight worsening of 2 fingernails at follow-up – finger 3 for patient 2 and finger 4 for patient 3 – not judged however relevant for us and them. The non-treated hand showed, at the end of the study, a NAPSI of 34, 23, and 12 maintained as such at follow-up.

Table 1.

Evolution of NAPSI according to each finger of patient 1, 2, and 3

Baseline NAPSI12 weeks of treatment NAPSI12 weeks of follow-up NAPSI
Patient 1 
 Finger 1 
 Finger 2 
 Finger 3 
 Finger 4 
 Finger 5 
 Total 36 
Patient 2 
 Finger 1 
 Finger 2 
 Finger 3 
 Finger 4 
 Finger 5 
 Total 35 
Patient 3 
 Finger 1 
 Finger 2 
 Finger 3 
 Finger 4 
 Finger 5 
 Total 20 
Baseline NAPSI12 weeks of treatment NAPSI12 weeks of follow-up NAPSI
Patient 1 
 Finger 1 
 Finger 2 
 Finger 3 
 Finger 4 
 Finger 5 
 Total 36 
Patient 2 
 Finger 1 
 Finger 2 
 Finger 3 
 Finger 4 
 Finger 5 
 Total 35 
Patient 3 
 Finger 1 
 Finger 2 
 Finger 3 
 Finger 4 
 Finger 5 
 Total 20 
Fig. 1.

Patient 2, finger 5, which evolved from baseline NAPSI 8 to 2 after 12 weeks of treatment and maintained a NAPSI 2 after 12 weeks of follow-up.

Fig. 1.

Patient 2, finger 5, which evolved from baseline NAPSI 8 to 2 after 12 weeks of treatment and maintained a NAPSI 2 after 12 weeks of follow-up.

Close modal

These preliminary data, despite the use in 3 patients only, suggest a potential use of topical tofacitinib 2% for nail psoriasis. Further studies on bigger groups are however necessary to confirm the present encouraging results and establish the effectiveness and safety also in more severe cases or in the pediatric population.

We had the chance to receive the ointment for compassionate use, and this is the main reason why the number of patients treated is limited. JAK inhibitor are, even in their topical formulas, extremely expensive and not always accepted by patients if not reimbursed by insurances. Topical formula might be however better accepted due to the absence (at least till now) of side effects. During the study and at the end, no side effect was, in fact, reported by patients who referred a very good tolerability and no skin irritation.

Available and effective topical products for nail psoriasis are limited, especially when the disease is localized in the matrix area [4]. Associations of calcipotriol and betamethasone dipropionate are useful, in particular for nail bed disease. Topical tazarotene 0.1% is another good option but irritation of the nail folds is a frequent side effect. Both calcipotriol/betamethasone and tazarotene are however unable to reach the nail matrix if applied on the proximal nail fold, so they are almost useless for nail matrix disease. In this case, a high-potency steroid, like clobetasol propionate 0.05%, can be a better option, but it has been proven that if applied for long time, it may cause bone atrophy [9, 10]. Intralesional monthly injections of triamcinolone acetonide 5–10 mg/mL are more appropriate in this case but they might be unaccepted by patients being a possible fear-provoking procedure.

Within this context, tofacitinib 2% ointment play a role quite important, in our opinion, for patients that refuse steroid treatment or for those where any available topical treatment is effective, regardless of an associated systemic treatment that might be ineffective on nails or might be interrupted by patients due to skin clearance before showing results on nails that notoriously require more time than skin to heal.

This study was a non-dominant hand study and not a randomized study because we judged easier and more acceptable for patients to apply the compound in fingernails of one hand only instead in at random fingernails. The choice to ask them to apply treatment only in the fingernails of the non-dominant hand was based on the fact that we wanted nail psoriasis stable and poorly exacerbated by traumas that a dominant hand might suffer.

All patients have given their written informed consent to publish their case, including images. This study protocol was reviewed and approved by “Comite de Etica da Universidade Estadual de Maringa,” approval No. 5.709.433.

The authors have no conflicts of interest to declare.

The authors did not receive any financial or any kind of support for this study.

Rachel Berbert Ferreira worked directly with the patients and revised the final approval of the version to be published; Sineida Berbert Ferreira worked directly with the patients and designed the study; Afonso Cesar Neves Neto revised the study critically and the final approval of the version to be published; Silvana Maria Assef analyzed all the data of the network and drafted the tables and figures; Lars Brichta drafted the work and revised it for intellectual content; Giovanni Damiani revised the study, the interpretation of the data, and final approval of the version to be published; Matilde Iorizzo worked directly with the patients, analyzed the data of the work and final approval of the version to be published.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

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