Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial.

BACKGROUND: Alopecia areata is characterised by non-scarring loss of scalp, face, or body hair. We investigated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, in patients with alopecia areata. METHODS: In this randomised, double-blind, multicentre, phase 2b-3 trial done at 118 sites in 18 countries, patients aged 12 years and older with alopecia areata and at least 50% scalp hair loss were randomly assigned to oral ritlecitinib or placebo once-daily for 24 weeks, with or without a 4-week loading dose (50 mg, 30 mg, 10 mg, 200 mg loading dose followed by 50 mg, or 200 mg loading dose followed by 30 mg), followed by a 24-week extension period during which ritlecitinib groups continued their assigned doses and patients initially assigned to placebo switched to ritlecitinib 50 mg or 200 mg loading dose followed by 50 mg. Randomisation was done by use of an interactive response system and was stratified by baseline disease severity and age. The sponsor, patients, and investigators were masked to treatment, and all patients received the same number of tablets to maintain masking. The primary endpoint was Severity of Alopecia Tool (SALT) score 20 or less at week 24. The primary endpoint was assessed in all assigned patients, regardless of whether they received treatment. This study was registered with ClinicalTrials.gov, NCT03732807. FINDINGS: Between Dec 3, 2018, and June 24, 2021, 1097 patients were screened and 718 were randomly assigned to receive ritlecitinib 200 mg + 50 mg (n=132), 200 mg + 30 mg (n=130), 50 mg (n=130), 30 mg (n=132), 10 mg (n=63), placebo to 50 mg (n=66), or placebo to 200 mg + 50 mg (n=65). 446 (62%) of 718 patients were female and 272 (38%) were male. 488 (68%) were White, 186 (26%) were Asian, and 27 (4%) were Black or African American. Of 718 patients randomly assigned, 104 patients discontinued treatment (34 withdrew, 19 adverse events [AEs], 12 physician decision, 12 lack of efficacy, 13 lost to follow up, five rolled over to long-term study transfer, four pregnancies, two protocol deviations, one declined to attend follow-up due to COVID-19, one attended last visit very late due to COVID-19, and one non-compliance). At week 24, 38 (31%) of 124 patients in the ritlecitinib 200 mg + 50 mg group, 27 (22%) of 121 patients in the 200 mg + 30 mg group, 29 (23%) of 124 patients in the 50 mg group, 17 (14%) of 119 patients in the 30 mg group, and two (2%) of 130 patients in the placebo group had a response based on SALT score 20 or less. The difference in response rate based on SALT score 20 or less between the placebo and the ritlecitinib 200 mg + 50 mg group was 29·1% (95% CI 21·2-37·9; p<0·0001), 20·8% (13·7-29·2; p<0·0001) for the 200 mg + 30 mg group, 21·9% (14·7-30·2; p<0·0001) for the 50 mg group, and 12·8% (6·7-20·4; p=0·0002) for the 30 mg group. Up to week 48 and including the follow-up period, AEs had been reported in 108 (82%) of 131 patients in the ritlecitinib 200 mg + 50 mg group, 105 (81%) of 129 patients in the 200 mg + 30 mg group, 110 (85%) of 130 patients in the 50 mg group, 106 (80%) of 132 patients in the 30 mg group, 47 (76%) of 62 patients in the 10 mg group, 54 (83%) of 65 patients placebo to ritlecitinib 200 mg + 50 mg in the extension period, and 57 (86%) of 66 patients in the placebo to 50 mg group. The incidence of each AE was similar between groups, and there were no deaths. INTERPRETATION: Ritlecitinib was effective and well tolerated in patients aged 12 years and older with alopecia areata. Ritlecitinib might be a suitable treatment option for alopecia areata in patients who are candidates for systemic therapy. FUNDING: Pfizer.

COVID-19 in Individuals Treated With Long-Term Hydroxychloroquine: A Propensity Score-Matched Analysis of Cicatricial Alopecia Patients.

Early in the COVID-19 pandemic, anti-malarial agent hydroxychloroquine (HCQ) was touted as a potentially effective COVID-19 treatment due to its purported antiinflammatory and antiviral effects.

Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial.

Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (clinicaltrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200 mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P < 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03-0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.

Trichodynia and telogen effluvium in COVID-19 patients: Results of an international expert opinion survey on diagnosis and management.

BACKGROUND: The cutaneous manifestations of COVID-19 may be useful disease markers and prognostic indicators. Recently, postinfectious telogen effluvium and trichodynia have also been reported. OBJECTIVE: To evaluate the presence of trichodynia and telogen effluvium in patients with COVID-19 and describe their characteristics in relation to the other signs and symptoms of the disease. METHODS: Patients with a history of COVID-19 presenting to the clinics of a group of hair experts because of telogen effluvium and/or scalp symptoms were questioned about their hair signs and symptoms in relation to the severity of COVID-19 and associated symptoms. RESULTS: Data from 128 patients were collected. Telogen effluvium was observed in 66.3% of the patients and trichodynia in 58.4%. Trichodynia was associated with telogen effluvium in 42.4% of the cases and anosmia and ageusia in 66.1% and 44.1% of the cases, respectively. In majority (62.5%) of the patients, the hair signs and symptoms started within the first month after COVID-19 diagnosis, and in 47.8% of the patients, these started after 12 weeks or more. LIMITATIONS: The recruitment of patients in specialized hair clinics, lack of a control group, and lack of recording of patient comorbidities. CONCLUSION: The severity of postviral telogen effluvium observed in patients with a history of COVID-19 infection may be influenced by COVID-19 severity. We identified early-onset (<4 weeks) and late-onset (>12 weeks) telogen effluvium.

Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial.

Background The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into type II pneumocytes is dependent on a modification of viral spike proteins by transmembrane protease serine 2 (TMPRSS2) expressed on the surface of human cells. TMPRSS2 is regulated by the androgen receptor, hence, SARS-CoV-2 infectivity is indirectly dependent on androgenic status and phenotype. Previously, we have reported that men affected by androgenetic alopecia (AGA) are overrepresented in severe coronavirus disease 2019 (COVID-19). Additionally, we have reported that men taking antiandrogenic drugs, e.g., 5-alpha-reductase inhibitors (5ARis), are less likely to have severe COVID-19. Here we aimed to test whether the androgen receptor antagonist, Proxalutamide, would be a beneficial treatment for subjects with SARS-CoV-2 infection. Methods Male and female subjects were recruited to a double-blinded, randomized, prospective, investigational study of Proxalutamide for the treatment of COVID-19. Mild to moderate, non-hospitalized subjects, who were confirmed positive for SARS-CoV-2, were treated with either Proxalutamide 200 mg/day or placebo. Endpoints for the study were remission time (days) and the percentage of subjects confirmed negative for SARS-CoV-2 on Day 7 after treatment. A negative SARS-CoV-2 test was defined by concentration-time (Ct)>40 determined by real-time reverse transcription-polymerase chain reaction (rtPCR). Results Two-hundred thirty-six (2360 subjects were included in the study (108 female, 128 male); 171 were randomized to the Proxalutamide arm and 65 were in the placebo group. On Day 7, SARS-CoV-2 became non-detectable with rtPCR (cT>40) in 82% of the subjects in the Proxalutamide group versus 31% in the placebo group (p < 0.001). The average clinical remission time for patients treated with Proxalutamide was 4.2 ±5.4 days versus 21.8 ±13.0 days in the placebo arm (p < 0.001). Conclusion Proxalutamide significantly accelerated viral clearance on Day 7 in mild to moderate COVID-19 patients versus placebo. Further, the time to clinical remission was significantly reduced in patients treated with Proxalutamide versus placebo.

A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - A potential clue to the role of androgens in COVID-19 severity.

A preliminary observation of high frequency of male pattern hair loss among admitted COVID-19 patients and suggest that androgen expression might be a clue to COVID-19 severity.