JAMA dermatology最新文献

Importance: The incidence of epidermal necrolysis (EN), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), varies across studies. While in-hospital mortality rates range from 15% to 20%, contributors to long-term mortality have been rarely evaluated and remain unknown.

Objective: To assess the incidence of and compare factors associated with in-hospital mortality and postdischarge mortality and sequelae among patients with EN.

Design, setting, and participants: This cohort study used French Health System data from January 1, 2013, to December 31, 2022, and included all adult patients (aged ≥18 years) with EN identified using International Statistical Classification of Diseases, Tenth Revision codes combined with a validated algorithm.

Exposure: Epidermal necrolysis.

Main outcomes and measures: Incidence, in-hospital mortality, postdischarge mortality, and sequelae were assessed as main outcomes. Factors associated with mortality were assessed using a multivariable Cox proportional hazards model.

Results: A total of 1221 adult patients with EN (median [IQR] age, 66 [49-79] years; 688 females [56.3%]) were included. Incidence was 2.6 (95% CI, 2.5-2.7) cases per million person-years. The in-hospital mortality rate was 19% (95% CI, 17%-21%) and postdischarge mortality rate, 15% (95% CI, 13%-17%) for an overall mortality of 34% (95% CI, 31%-36%). In multivariable analysis, factors associated with in-hospital mortality were age (adjusted hazard ratio [AHR], 1.03 per year of age; 95% CI, 1.02-1.04 per year of age), history of cancer (AHR, 2.04; 95% CI, 1.53-2.72), dementia (AHR, 1.85; 95% CI, 1.12-3.07), liver disease (AHR, 1.81; 95% CI, 1.24-2.64), and EN severity (TEN vs SJS: AHR, 2.14; 95% CI, 1.49-3.07). Cancer, liver disease, and dementia remained associated with postdischarge mortality (AHR, 3.26 [95% CI, 2.35-4.53], 1.86 [95% CI, 1.11-3.13], and 1.95 [95% CI, 1.11-3.43], respectively). Conversely, EN initial severity was not associated with mortality after hospital discharge (TEN vs SJS: AHR, 0.95; 95% CI, 0.60-1.47), but acute complications remained associated (AHR, 2.14 [95% CI, 1.26-3.63] and 2.44 [95% CI, 1.42-4.18] for acute kidney injury and sepsis, respectively). The main sequelae were ophthalmologic and mood disorders.

Conclusion: The findings of this cohort study suggest that although EN is a rare condition, it is associated with high rates of in-hospital and postdischarge mortality among patients who are older and have comorbid conditions. However, in contrast with in-hospital mortality, postdischarge mortality is not associated with EN initial severity but with acute in-hospital complications (eg, acute kidney injury and sepsis). Future studies are needed to construct models to estimate long-term outcomes and sequelae in patients with EN.

Importance: Baricitinib has demonstrated efficacy for treating severe alopecia areata in adults. There is currently limited information about the need for continuous therapy after achieving scalp hair regrowth.

Objective: To report results from the randomized withdrawal period of the BRAVE-AA1 trial.

Design, setting, and participants: BRAVE-AA1 was a randomized, placebo-controlled, phase 3 randomized clinical trial with a treatment withdrawal substudy that was conducted at 70 centers in 3 countries beginning in March 2019. It included 654 adults with severe alopecia areata (AA) (Severity of Alopecia Tool [SALT] score ≥50) who were randomized 3:2:2 to receive treatment with baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Data were analyzed in August 2023.

Intervention: At week 52, 154 patients who were responders (SALT score ≤20) were rerandomized 3:1 to continue to take their current dose of baricitinib or transition to placebo (randomized withdrawal). Responders randomized to placebo who experienced a loss of treatment benefit (>20-point worsening in SALT score) at any time after week 52 were retreated with their original baricitinib dose.

Main outcome and measures: The proportion of patients who lost treatment benefit through week 152 and the proportion of patients who recaptured response after retreatment. The last observation carried forward was used to impute missing or censored data.

Results: Of 654 patients who received treatment, the mean (SD) age was 37.1 (13.0) years, and there were 383 women (58.6%). At week 52, 10 of 39 responders taking baricitinib, 2 mg, and 30 of 115 responders taking baricitinib, 4 mg, were rerandomized to placebo. At 4 and 8 weeks of treatment withdrawal, 0% and 10% to 11% of patients, respectively, lost treatment benefit regardless of dose. At week 152, 80% of patients had lost benefit compared with 7% for those who continued baricitinib therapy for both dose groups. Within the follow-up observation periods, 5 of 8 patients taking 2 mg (63%) and 21 of 24 patients taking 4 mg (87.5%) recaptured a SALT score of 20 or less response after retreatment.

Conclusions and relevance: Severe AA is a chronic, relapsing condition, and this randomized clinical trial found that withdrawal of therapy for a patient population with severe AA who had achieved meaningful hair regrowth after 1 year of treatment with baricitinib resulted in loss of benefit for almost all patients, indicating that continued therapy is required to maintain hair regrowth.

Trial registration: ClinicalTrials.gov Identifier: NCT03570749.