Efficacy and safety of ritlecitinib in adolescents with alopecia areata: Results from the ALLEGRO phase 2b/3 randomized,double-blind,placebo-controlled trial

Background/Objectives

This subgroup analysis of the ALLEGRO phase 2b/3 trial (NCT03732807) evaluated the efficacy and safety of ritlecitinib, an oral, selective dual JAK3/TEC family kinase inhibitor, for the treatment of alopecia areata (AA) in patients aged 12–17 years.

Methods

In ALLEGRO-2b/3, patients aged ≥12 years with AA and ≥50% scalp hair loss received once-daily ritlecitinib 50 or 30 mg (±4-week 200-mg loading dose) or 10 mg or placebo for 24 weeks. In a subsequent 24-week extension period, ritlecitinib groups continued their doses, and patients initially assigned to placebo switched to 200/50 or 50 mg daily. Clinician- and patient-reported hair regrowth outcomes and safety were assessed.

Results

In total, 105 adolescents were randomized. At Week 24, 17%–28% of adolescents achieved a Severity of Alopecia Tool (SALT) score ≤20 (≤20% scalp without hair) in the ritlecitinib 30 mg and higher treatment groups versus 0% for placebo. At Week 48, 25%–50% of patients had a SALT score ≤20 across ritlecitinib treatment groups (30 mg and higher). Adolescents reporting that their AA “moderately” or “greatly” improved were 45%–61% in the ritlecitinib groups (30 mg and higher) (vs. 10%–22% for placebo) at Week 24 and 44%–80% at Week 48. The most common adverse events in adolescents were headache, acne, and nasopharyngitis. No deaths, major adverse cardiovascular events, malignancies, pulmonary embolisms, opportunistic infections, or herpes zoster infections were reported.

Conclusion

Ritlecitinib treatment demonstrated clinician-reported efficacy, patient-reported improvement, and an acceptable safety profile through Week 48 in adolescents with AA with ≥50% scalp hair loss.     

Janus kinase inhibitors: An innovative treatment for alopecia areata

Alopecia areata (AA) is a relatively common disease, but no satisfactory treatment has yet been developed. Recently, research progress has been made in the pathogenesis of AA, revealing that autoreactive cytotoxic T cells are important and that the Janus kinase (JAK) pathway is involved. Therefore, the potential of JAK inhibitors as therapeutic agents for AA is attracting attention. Several single‐arm clinical trials and retrospective studies demonstrated that oral JAK inhibitors are effective and tolerable treatments for moderate to severe AA. Although JAK inhibitors are emerging as an innovative treatment for AA, further placebo‐controlled clinical trials are required to confirm their efficacy and long‐term safety.     

The relative efficacy of monotherapy with Janus kinase inhibitors,dupilumab and apremilast in adults with alopecia areata: Network meta-analyses of clinical trials

Background

Janus kinase (JAK) inhibitors, biologics, and phosphodiesterase-4 (PDE-4) inhibitors are recent therapies for alopecia areata (AA)—albeit, knowledge gaps exist for these agents' relative efficacy.

Objectives

We determined the relative efficacy and safety of monotherapy with the aforementioned agents in adults with AA.

Methods

The literature was systematically searched; we used data from randomized trials that investigated the agents' efficacy—as per Severity of Alopecia Tool (SALT) scores. Bayesian network meta-analyses were used to determine relative efficacy and safety. Effect modification was determined using a generalized linear model on aggregate data; evidence quality was evaluated.

Results

Based on the surface under the cumulative ranking curve estimates obtained from multiple efficacy endpoints, regimens with the highest likelihood of achieving percent reduction in SALT scores, as well as a minimum 90%, 75% or 50% reduction in SALT scores are (in alphabetical order) baricitinib 4 mg once daily (QD), brepocitinib 60/30 mg QD, deuruxolitinib (CTP-543) 12 mg twice daily (BID), ritlecitinib 200/50 mg QD, ruxolitinib 20 mg BID and tofacitinib 5 mg BID. In contrast, dupilumab subcutaneous injections administered weekly and apremilast 30 mg BID were less likely to be effective. Discontinuation due to any adverse event was the least likely with oral JAK inhibitors, and more likely with dupilumab and apremilast.

Conclusions

Our results support the conduct of high-quality comparative trials to determine whether JAK inhibitors are more effective and safer than PDE4 inhibitors.     

JAK抑制剂治疗斑秃的研究进展

【摘要】 斑秃是一种突然发生的局限性脱发,严重者可进展为全秃或普秃。目前认为斑秃是一种具有遗传背景的器官特异性自身免疫性疾病,毛囊免疫赦免结构的破坏是重要的发病机制。目前,斑秃的治疗方法有口服、外用、肌内或局部皮损内注射糖皮质激素、外用米诺地尔酊等,但仍有一部分患者治疗无效。近年来,国外开展了很多有关JAK抑制剂治疗斑秃的临床试验。研究显示,在采用口服JAK抑制剂治疗的患者中,约半数中重度斑秃患者在治疗后毛发几乎完全长出,疗效较明显。也有报道外用鲁索替尼治疗斑秃,但疗效不一。尽管部分患者在停药后复发或是在治疗过程中出现感染等不良反应,JAK抑制剂确实为有效治疗中重度斑秃提供了一种选择。     

Alopecia areata: Clinical presentation, diagnosis, and unusual cases

Alopecia areata (AA) is a nonscarring hair loss disorder with a 2% lifetime risk. Most patients are below 30 years old. Clinical types include patchy AA, AA reticularis, diffuse AA, AA ophiasis, AA sisiapho, and perinevoid AA. Besides scalp and body hair, the eyebrows, eyelashes, and nails can be affected. The disorder may be circumscribed, total (scalp hair loss), and universal (loss of all hairs). Atopy, autoimmune thyroid disease, and vitiligo are more commonly associated. The course of the disease is unpredictable. However, early, long‐lasting, and severe cases have a less favorable prognosis. The clinical diagnosis is made by the aspect of hairless patches with a normal skin and preserved follicular ostia. Exclamations mark hairs and a positive pull test signal activity. Dermoscopy may reveal yellow dots. White hairs may be spared; initial regrowth may also be nonpigmented. The differential diagnosis includes trichotillomania, scarring alopecia, and other nonscarring hair loss disorders such as tinea capitis and syphilis.     

斑秃的外用药物治疗

外用药物在斑秃治疗中具有重要作用,本文就外用糖皮质激素、致敏剂二苯基环丙烯酮和斯夸酸二丁酯、蒽林、米诺地尔、比马前列素、维A酸、贝沙罗汀、卡泊三醇、辣椒碱、壬二酸、大蒜凝胶和洋葱汁治疗斑秃的在斑秃中的应用进行综述。     

蛇形脱发和W形脱发嵌合分布1例

报道1例特殊表现的斑秃，患者男，7岁。头部脱发4年，表现为双颞部沿发际呈带状的蛇形脱发和前额沿发际呈W形脱发嵌台分布，经治疗皮损无明显变化。     

光疗法在斑秃中的应用

近年来,光疗治疗斑秃取得较好疗效。本文对PUVA疗法、长波紫外线A1、308nm单频准分子光和准分子激光、红外线,低能量激光疗法及点阵二氧化碳激光在斑秃治疗中的应用进行综述。     

斑秃患者甲改变的观察

本文观察了斑秃163例的甲片变化,其发生率为65.64%.但甲片变化与斑秃的严重程度、病程均无明显关系.甲片变化多为甲凹点.     

76例重型斑秃的临床分析

目的 :探讨重型斑秃的临床特征。方法 :回顾分析了近 4年诊治的 76例重型斑秃病例。结果 :重型斑秃中女性患者的病程比男性患者长 (P <0 0 5 ) ,与重型斑秃中的斑秃相比 ,甲异常改变更多见于全秃和普秃患者 (P <0 0 5 ) ,有家族斑秃史患者与无家族斑秃史患者比较 ,两者的初次发病年龄有显著性差异 (P <0 0 5 ) ,发病前伴有精神神经因素诱发者比无伴有精神神经因素诱发者病程要短 (P <0 0 5 )。结论 :女性重型斑秃患者可能病程更容易持续延绵、迁移反复 ,重型斑秃中有家族斑秃史者 ,它的发病年龄更早 ,甲异常改变不但多见于病程较长、病情顽固、反复的患者 ,而且也多见于病情较重的患者 ,全秃和普秃患者甲异常改变更多见 ,重型斑秃的治疗应注意精神因素的影响及强调综合治疗。     

Is Helicobacter pylori infection associated with alopecia areata?

Background  Alopecia areata (AA) is an immune-mediated form of hair loss that occurs in all ethnic groups, ages, and both sexes. Helicobacter pylori has been associated with certain extra-digestive dermatological conditions, including chronic urticaria, rosacea, Schönlein-Henoch purpura, Sweet syndrome, systemic sclerosis, and atopic dermatitis.
Objective  The causal relation between alopecia areata and H. pylori is discussed. We have screened for the presence of H. pylori in patients with AA in order to determine any potential role in its pathophysiology.
Patients and methods  We have prospectively studied 31 patients with AA and 24 healthy volunteers of similar gender for the presence of H. pylori surface antigen (HpSag) in stool.
Results  Optical density values for H. pylori infection were positive in 18 of all 31 patients evaluated (58.1%), while in 13 patients, values did not support H. pylori infection (41.9%). While in the control group, 10 of 24 (41.7%) had positive results. Within the group of AA, there was no significant difference between HpSag-positive and HpSag-negative patients.
Conclusions  Based on these results, the relation between H. pylori and AA is not supported. We advise that H. pylori detection should not be included in the laboratory workup of AA.     

Investigative guidelines for alopecia areata

The reported efficacy of various treatments for alopecia is difficult to compare based on a general lack of consideration in case reports/series and clinical trials of the spontaneous regrowth or baseline prognostic factors seen in alopecia areata and a general lack of quantification of hair growth. This report will give both the investigator and clinician guidelines for clinical trial design that will take into account variables known to effect efficacy results such as baseline severity, pattern, and duration of hair loss, age of the subject, and concomitant conditions that may impact on potential regrowth. Reliable methods of assessment of efficacy and response criteria that will enable direct comparison of results between agents will also be discussed.