Treatment outcome of oral tofacitinib and ruxolitinib in patients with alopecia areata: A systematic review and meta-analysis.

BACKGROUND: Tofacitinib and ruxolitinib have been used off-label to treat alopecia areata. Although a number of case reports and small studies have been published, there are no comprehensive reviews examining the outcomes of using tofacitinib and ruxolitinib for the treatment of alopecia areata. AIMS: The aim of the study was to examine the outcome of patients with alopecia areata treated with oral tofacitinib or ruxolitinib in previously published studies. METHODS: A search of MEDLINE, Embase and Cochrane library was conducted. A systematic review and meta-analysis were performed focusing on the Severity of Alopecia Tool 50 achievement rate, the frequency of adverse events and recurrence after discontinuation of treatment. RESULTS: A total of 1244 studies were identified of which only 12 studies met the inclusion criteria. Of the 346 patients in these 12 studies, 288 had received oral tofacitinib and 58 had received oral ruxolitinib. The overall Severity of Alopecia Tool50 achievement rate was 66% (95% confidence interval, 54%-76%). Subgroup analysis revealed that drug choice, mean age, sex ratio and alopecia areata subtype ratio did not significantly affect the treatment response. Infections and laboratory abnormalities were the most common adverse events (98 and 65 cases of 319 patients, respectively). Patients treated for more than six months had a greater frequency of laboratory abnormalities as compared to those treated for shorter durations (24% vs. 7%; P = 0.04). Recurrence of alopecia areata was observed within three months after discontinuation of treatment in the majority (74%) of patients. LIMITATIONS: This analysis was limited by the small number of observational studies available for review, the heterogeneity of patient characteristics and the lack of long-term data. CONCLUSION: Both oral tofacitinib and ruxolitinib are effective and well tolerated in the treatment of alopecia areata. Clinicians should be aware of the expected efficacy, adverse events and high recurrence rate of oral JAK inhibitors for alopecia areata to effectively counsel these patients before starting therapy.

Leucine-rich repeat kinase 2 inhibitors: a patent review (2014-2016).

INTRODUCTION: Leucine-rich repeat kinase 2 (LRRK2) is a member of the Tyrosine Kinase-Like (TKL) branch of the kinome tree and is a multi-domain protein that includes GTPase and kinase activity. While genome-wide association studies (GWAS) has linked LRRK2 with Crohn's disease and leprosy, it has received the greatest attention due to it being implicated as one of the genetic loci associated with autosomal dominant inheritance in Parkinson's disease (PD). Areas covered: In this review, the small molecule patent literature from 2014-2016 with a focus on composition of matter and use patents was surveyed. Scifinder was primarily searched using 'LRRK2' as the query to identify all relevant literature and then triaged for small molecule patents. Expert opinion: The patent landscape around LRRK2 continues to develop. The early patents covered using existing kinase inhibitors for use against LRRK2. This evolved to compounds specifically designed for selectivity against LRRK2, but key exemplified compounds lacked sufficient brain exposure to affect sufficient efficacy. More recent compounds have addressed this deficiency and show greater potential for treating PD. While potency will be necessary to generate medicines with low human daily doses, brain penetration and safety will be the key differentiators for ultimately determining the most effective LRRK2 disease-modifying treatment for PD.