piperidines and Nail-Diseases

Various systemic immunomodulating therapies have been investigated to treat nail psoriasis, but the efficacy remains unclear.. To perform a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis.. Eligible studies in online databases were identified until March 10, 2020. To assess the efficacy of small molecule inhibitors and biologics, network meta-analyses with surface under the cumulative ranking curve of improvement in nail score at 10 to 16 and at 24 to 26 weeks, as well as 100% improvement of Nail Psoriasis Severity Index (NAPSI), were performed.. Thirty-nine studies with a total of 13 treatment arms involving 15,673 patients with nail psoriasis were included. An network meta-analysis showed that tofacitinib (weighted mean difference, 56.67; 95% confidence interval [CI], 35.87-77.48) and ixekizumab (weighted mean difference, 59.40; 95% CI, 45.87-72.93) presented the most improvement of nail score at 10 to 16 weeks and 24 to 26 weeks, respectively. For 100% improvement of the Nail Psoriasis Severity Index, ixekizumab showed the best efficacy among all treatments (odds ratio, 2.98; 95% CI, 1.74-5.10).. Insufficiency of eligible data and no long-term follow-up data.. Tofacitinib and ixekizumab presented the best efficacy for treating nail psoriasis in 10 to 16 weeks and 24 to 26 weeks, respectively.

Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Dermatologic Agents; Etanercept; Humans; Infliximab; Nail Diseases; Network Meta-Analysis; Piperidines; Protein Kinase Inhibitors; Psoriasis; Pyrimidines; Severity of Illness Index

Tofacitinib is an oral Janus kinase inhibitor. Efficacy and safety of tofacitinib in patients with moderate-to-severe plaque psoriasis have been demonstrated.. We sought to assess the efficacy of tofacitinib for the treatment of nail psoriasis over a period of 52 weeks.. In 2 identical phase 3 studies (OPT Pivotal 1 and 2), patients were randomized 2:2:1 to receive tofacitinib 5 mg, tofacitinib 10 mg, or placebo, twice daily. At week 16, placebo-treated patients were re-randomized to tofacitinib. This post hoc analysis of patients with existing nail psoriasis assessed the Nail Psoriasis Severity Index (NAPSI) score and proportions of patients achieving ≥50% reduction in NAPSI from baseline (NAPSI50), NAPSI75, or NAPSI100.. Baseline mean NAPSI scores for patients treated with tofacitinib 5 mg (N = 487), tofacitinib 10 mg (N = 476), and placebo (N = 233) twice daily were 27.0, 27.3, and 26.9, respectively. At week 16, significantly (all P < .05) more patients receiving tofacitinib 5 mg and tofacitinib 10 mg versus placebo twice daily achieved NAPSI50 (32.8%, 44.2% vs 12.0%), NAPSI75 (16.9%, 28.1% vs 6.8%), and NAPSI100 (10.3%, 18.2% vs 5.1%), respectively. Improvements were sustained to week 52.. Limitations include discontinuation of clinical nonresponders at week 28.. Tofacitinib treatment resulted in improvements in nail psoriasis versus placebo at week 16; improvements were maintained over 52 weeks [NCT01276639; NCT01309737].

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Double-Blind Method; Female; Humans; Male; Middle Aged; Nail Diseases; Piperidines; Protein Kinase Inhibitors; Psoriasis; Pyrimidines; Pyrroles; Time Factors; Treatment Outcome; Young Adult

Ibrutinib, a Bruton tyrosine kinase inhibitor, is a new targeted agent approved by the US Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma, and Waldenström macroglobulinemia. Ibrutinib is overall well tolerated but long-term treatment is required until disease progression or intolerable toxic effects occur. Little is known regarding its cutaneous adverse effects.. To describe the hair and nail manifestations associated with the long-term use of ibrutinib for the treatment of CLL.. Prospective study of 66 patients with CLL enrolled in a single-arm phase 2 clinical trial of ibrutinib for CLL between March 2014 and October 2015 at the National Institutes of Health.. The primary outcome, nail and hair changes associated with ibrutinib therapy, was assessed by an 11-question survey. In addition, the severity of nail changes was determined from a 0 to 3 rating scale for both onychoschizia and onychorrhexis.. Among 66 patients (43 men and 23 women with ages ranging from 55 to 85 years), 44 (67%) reported brittle fingernails at a median of 6.5 (95% CI, 6-12) months after starting ibrutinib therapy. Fifteen patients (23%) developed brittle toenails after a median of 9 (95% CI, 6-15) months of ibrutinib therapy. Textural hair changes were reported in 17 patients (26%), at a median of 9 (95% CI, 6-12) months of ibrutinib treatment.. Hair and nail abnormalities are commonly associated with ibrutinib and appear several months after initiating therapy. Ibrutinib inhibits Bruton tyrosine kinase by covalently binding to cysteine 481. Whether ibrutinib affects the hair and nails by binding and altering cysteine-rich proteins of hair and nails or by means of another mechanism remains unknown.. clinicaltrials.gov Identifier: NCT01500733.

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Aged; Aged, 80 and over; Antineoplastic Agents; Female; Hair Diseases; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Nail Diseases; Piperidines; Prospective Studies; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines; Severity of Illness Index; Time Factors

Nail involvement is common in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, which has a strong association with quality of life in patients with SAPHO. Tofacitinib is an oral Janus kinase inhibitor that has been previously shown to be effective for nail psoriasis.. To assess the efficacy and safety of tofacitinib for the treatment of nail involvement in SAPHO syndrome.. Participants received tofacitinib, 5 mg, twice daily, for 12 weeks.. This open-label, single-arm, prospective pilot study included 13 patients with SAPHO syndrome accompanied by nail lesions and active palmoplantar pustulosis who were recruited from Peking Union Medical College Hospital from September 2019 to December 2019. Follow-up was completed in March 2020. Analysis began March 2020.. The primary end point was the percentage of the change from baseline in Nail Psoriasis Severity Index scores at week 12. Secondary end points included the percentage of the change from baseline in Palmoplantar Psoriasis Area and Severity Index scores, change from baseline in Visual Analogue Scale scores in global osteoarticular pain, Dermatology Life Quality Index scores, and inflammatory markers. Adverse events were recorded throughout the study.. Thirteen female Asian patients (means [SD] age, 39.7 [12.3] years) were included, all of whom completed the study. At week 12, significant improvements were observed in Nail Psoriasis Severity Index scores (median, -67% [interquartile range (IQR), -56% to -77%]; P < .001) and Palmoplantar Psoriasis Area and Severity Index scores (median, -71% [IQR, -58% to -78%]; P < .001). Significant improvement was also noted in Dermatology Life Quality Index scores (median, -12 [IQR, -8.5 to -15]; P < .001) at week 12. A significant decrease in Visual Analogue Scale scores in global osteoarticular pain was observed at week 8 (median, -4 [IQR, 0 to -5]; P = .02) but was not significant at week 12. Inflammatory marker levels were decreased, as indicated by erythrocyte sedimentation rate (median, -8 mm/h [IQR, -4 mm/h to -11 mm/h]; P < .001) and high-sensitivity C-reactive protein levels (median, -1.6 [IQR, -0.3 to -4.1]; P = .01). No severe adverse events were observed.. In this pilot study, tofacitinib yielded significant remission of nail lesions and palmoplantar psoriasis accompanied by an improvement in quality of life in patients with SAPHO syndrome. Additional follow-up studies to evaluate the long-term efficacy and safety of tofacitinib for nail involvement in SAPHO syndrome are warranted.. Chinese Clinical Trial Registry number: ChiCTR1900025941.

Topics: Acquired Hyperostosis Syndrome; Adult; Arthralgia; Child; Female; Humans; Middle Aged; Nail Diseases; Pain Measurement; Pilot Projects; Piperidines; Prospective Studies; Psoriasis; Pyrimidines; Quality of Life; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Alopecia; Female; Humans; Janus Kinase Inhibitors; Lichen Planus; Middle Aged; Nail Diseases; Piperidines; Pyrimidines; Treatment Outcome

A few anecdotal case reports demonstrated that tofacitinib improved nail changes associated with AA.. To investigate nail changes in patients with AA treated with tofacitinib and evaluate the relationship between nail and hair responses to tofacitinib.. This is a retrospective study of 33 adult patients with moderate-to-severe AA treated with oral tofacitinib monotherapy for at least 4 months.. Fifteen patients had nail involvement and demonstrated more severe hair loss than those without nail involvement (p = .040). However, there was no significant difference in hair regrowth between two groups. Of 15 patients with nail involvement, 11 (73.3%) showed improvement regardless of type of nail change; the first improvement was observed at a median of 5 months (range, 1-11) after administration. Nail improvement was associated with neither initial severity of hair loss nor hair response to tofacitinib. Nail improvement tended to occur later than hair regrowth.. Oral tofacitinib monotherapy improves nail involvement associated with AA. Nail involvement is not a poor prognosis factor in hair regrowth with tofacitinib treatment and there is no evident relationship between nail and hair responses.

Topics: Administration, Oral; Adult; Alopecia Areata; Female; Humans; Male; Middle Aged; Nail Diseases; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies

Nail dystrophy is a heterogeneous skin condition and in some subtypes, is associated with autoimmune diseases in particular psoriasis and psoriatic arthritis. In this report, we show that tofacitinib, a novel therapy for rheumatoid arthritis, appears to be beneficial in patients with nail disease refractory to other conventional modes of therapy.

Topics: Adult; Alopecia; Female; Humans; Male; Nail Diseases; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Treatment Outcome

Topics: Adult; Alopecia; Female; Humans; Janus Kinases; Male; Nail Diseases; Nails; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles