Publications

Reversible axonal swelling and brainstem auditory evoked potential (BAEP) changes were observed in standard chronic (9-month) toxicology studies in dogs treated with ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor, at exposures higher than the approved 50-mg human dose. To evaluate the clinical relevance of the dog toxicity finding, this phase 2a, double-blind study assessed BAEP changes and intraepidermal nerve fiber (IENF) histology in adults with alopecia areata treated with ritlecitinib. Patients were randomized to receive oral ritlecitinib 50 mg once daily (QD) with a 4-week loading dose of 200 mg QD or placebo for 9 months (placebo-controlled phase); they then entered the active-therapy extension and received ritlecitinib 50 mg QD (with a 4-week loading dose of 200 mg in patients switching from placebo). Among the 71 patients, no notable mean differences in change from baseline (CFB) in Waves I-V interwave latency (primary outcome) or Wave V amplitude on BAEP at a stimulus intensity of 80 dB nHL were observed in the ritlecitinib or placebo group at Month 9, with no notable differences in interwave latency or Wave V amplitude between groups. The CFB in mean or median IENF density and in percentage of IENFs with axonal swellings was minimal and similar between groups at Month 9. Ritlecitinib treatment was also not associated with an imbalanced incidence of neurological and audiological adverse events. These results provide evidence that the BAEP and axonal swelling finding in dogs are not clinically relevant in humans.

BACKGROUND: Alopecia areata (AA) is a hair loss disorder that can seriously impact quality of life. Janus kinase (JAK) inhibitors, including deuruxolitinib, have previously demonstrated significant hair regrowth in AA.

OBJECTIVE: The Phase 3 THRIVE-AA1 randomized, double-blinded, placebo-controlled trial (NCT04518995) evaluated the safety and efficacy of the oral JAK1/JAK2 inhibitor deuruxolitinib in adult patients with AA.

METHODS: Patients aged 18-65 years with ≥50% hair loss were randomized to deuruxolitinib 8 mg twice daily, deuruxolitinib 12 mg twice daily, or placebo for 24 weeks. The primary end point was the percentage of patients achieving a Severity of Alopecia Tool score ≤20. A key secondary end point was the percentage of satisfaction of hair patient-reported outcome responders.

RESULTS: Significantly higher proportions of patients taking deuruxolitinib met the primary end point (8 mg 29.6%; 12 mg 41.5% versus placebo 0.8%). Both deuruxolitinib doses achieved significant improvements in all secondary end points versus placebo, including satisfaction of hair patient-reported outcome (8 mg 42.1%; 12 mg 53.0% versus placebo 4.7%). Most treatment-emergent adverse events were mild or moderate, consistent with other oral JAK inhibitors.

LIMITATIONS: Further studies are required to understand longer-term safety, efficacy, and impact of treatment cessation.

CONCLUSION: Both doses of deuruxolitinib were effective for hair regrowth. Patient satisfaction aligned with hair growth.

BACKGROUND: To date, there is no comprehensive meta-analysis analyzing the association between alopecia areata, anxiety, and depression.

OBJECTIVE: We sought to analyze the existing literature to examine the association between alopecia areata, anxiety, and depression.

METHODS: We extracted literature from 4 databases including MEDLINE, Embase, PsychINFO, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (ie, PRISMA) reporting guidelines to finalize a list of relevant articles to be included in our systematic review and meta-analysis. There were no restrictions placed on publication year or age of participants.

RESULTS: Eight studies that included 6010 patients with AA and 20 961 control individuals were included in the quantitative analysis. These included 4 cross-sectional studies and 4 case-control studies. Analysis of these studies showed a positive association with anxiety (pooled odds ratio, 2.50; 95% confidence interval, 1.54-4.06) and depression (pooled odds ratio, 2.71; 95% confidence interval, 1.52-4.82).

LIMITATIONS: Publication bias may be a limitation of the study.

CONCLUSION: This study suggests that patients with AA are at higher risk of both anxiety and depression. Health care professionals must be cognizant of this higher risk and consider routine assessment of these conditions and referral to appropriate providers when indicated.

BACKGROUND: Despite high use of complementary and alternative medicine (CAM) for alopecia areata (AA), efficacy and safety remain unclear.

OBJECTIVE: To identify all CAM therapies studied for treatment of AA. Outcomes of interest included disease course and psychologic well-being.

METHODS: PubMed and Embase were searched to identify English articles containing original data investigating CAM in individuals with AA from 1950-2018. Quality was assessed with Oxford Centre for Evidence Based Medicine criteria.

RESULTS: Of 1015 initial citations, 16 articles met inclusion criteria: 5 randomized controlled trials, 5 prospective controlled cohorts, 4 prospective noncontrolled cohorts, 1 retrospective cohort, and 1 case series. CAM therapies with best evidence and efficacy for hair growth in AA include essential oil aromatherapy, topical garlic, and oral glucosides of peony with compound glycyrrhizin. Hypnosis and mindfulness psychotherapy represent low-quality evidence for improvement of psychologic and quality of life outcomes. Adverse events were rare and mild for all therapies evaluated.

LIMITATIONS: Inconsistent or poorly reported study methodology and nonstandardized outcomes limit the conclusions that can be made from these studies.

CONCLUSIONS: This work serves to inform physician treatment of patients with AA seeking CAM while encouraging further investigation into these therapies to address some of the therapeutic challenges of AA.

BACKGROUND: Hair loss causes significant psychosocial distress to patients. Health utility measurements offer an objective, quantitative assessment of health-related quality of life (QOL).

METHODS: We performed a prospective cohort study on patients with hair loss between January 1, 2018 and December 31, 2020. Patient metrics were compared with layperson perception of alopecia, prospectively collected between August 1 and December 31, 2017. Health utility measures were quantified using the visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO) in quality-adjusted life-years (QALYs) and relative to the minimal clinically important difference (MCID). Bonferroni correction to the significance threshold was performed.

RESULTS: Thirty-one patients with alopecia were compared with 237 laypeople. Patient metrics for female hair loss were all significantly lower than laypeople measures (VAS QALYs 0.65 ± 0.21 vs. 0.83 ± 0.18, p = 0.0001). Mean SG QALYs were lower for patients in the male alopecia state (0.86 ± 0.23 vs. 0.96 ± 0.12, p = 0.0278). Post-hair transplant improvement in TTO was significantly greater for patients (+ 0.08 ± 0.12 vs. + 0.02 ± 0.09, p = 0.0070) and significantly more often exceeded the MCID (45.2% vs. 16.9%, p = 0.0006).

CONCLUSIONS: Alopecia negatively impacts QOL, and the true patient experience is more taxing than what is perceived by laypeople. Hair transplantation improves QOL more for male patients than common perception.

LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .