Efficacy and safety of different JAK inhibitors in the treatment of alopecia areata: a network meta-analysis

Wei, Dongfan; Chen, Yi; Shen, Yuqing; Xie, Bo; Song, Xiuzu

doi:10.3389/fimmu.2023.1152513

Cited by 11 publications

(9 citation statements)

References 36 publications

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“…The oral JAK inhibitors investigated in our study (brepocitinib, ritlecitinib, baricitinib, deuruxolitinib, ivarmacitinib, and ATI501) were proven effective in promoting hair regrowth for moderate-to-severe AA, with the exception of ivarmacitinib 2mg and ritlecitinib 10mg. However, the two topically applied JAK inhibitors (delgocitinib ointment and ruxolitinib cream) seemed to have no effect on patients with moderate-to-severe AA, aligning with findings from previous studies ( Phan and Sebaratnam, 2019 ; Yan et al, 2022 ; Wei et al, 2023 ). Local delivery was designed to reduce the potential side effects of systemic administrations.…”

Section: Discussionsupporting

confidence: 86%

Comparative efficacy and safety of JAK inhibitors in the treatment of moderate-to-severe alopecia areata: a systematic review and network meta-analysis

Yan,

Wang,

Tang

et al. 2024

Front. Pharmacol.

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We performed a Bayesian network meta-analysis to indirectly compare the relative efficacy and safety of the latest JAK inhibitors for moderate-to-severe alopecia areata (AA). 13 trials totaling 3,613 patients were included. Two low-dose groups of oral formulations (ritlecitinib 10mg and ivarmacitinib 2mg) and two topical formulations (delgocitinib ointment and ruxolitinib cream) appeared to be relatively ineffective against moderate-to-severe AA. Ranking analysis suggested that brepocitinib 30mg has the best relative effect in reducing the SALT score (sucra = 0.9831), and demonstrated comparable efficacy to deuruxolitinib 12mg (sucra = 0.9245), followed by deuruxolitinib 8mg (sucra = 0.7736). Regarding the SALT50 response, brepocitinib 30mg ranked highest (sucra = 0.9567), followed by ritlecitinib 50mg (sucra = 0.8689) and deuruxolitinib 12mg (sucra = 0.7690). For achieving the SALT75 response, deuruxolitinib 12mg had the highest probability (sucra = 0.9761), followed by deuruxolitinib 8mg (sucra = 0.8678) and brepocitinib 30mg (sucra = 0.8448). Deuruxolitinib 12mg might be the most effective therapy for patients with severe AA (sucra = 0.9395), followed by ritlecitinib 50mg (sucra = 0.8753) and deuruxolitinib 8mg (sucra = 0.8070). Deuruxolitinib 12mg/8mg demonstrated notable efficacy for moderate-to-severe AA, and is expected to be a new treatment option for AA. It was worth noting that deuruxolitinib exhibit a greater likelihood of causing adverse events in comparison to other JAK inhibitors. Ritlecitinib 50mg seemed to exhibit fewer adverse effects in the high-dose groups of oral JAK inhibitors and might be an optimal choice to balance safety and efficacy. The majority of JAK inhibitors exhibited acceptable short-term safety profiles. To enhance the applicability and accuracy of our research, further head-to-head trials with longer follow-up periods are needed.Systematic Review Registration: identifier [CRD42022368012].

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Section: Discussionsupporting

confidence: 86%

Comparative efficacy and safety of JAK inhibitors in the treatment of moderate-to-severe alopecia areata: a systematic review and network meta-analysis

Yan,

Wang,

Tang

et al. 2024

Front. Pharmacol.

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“…Another smaller NMA has also been recently published. Nevertheless, this particular study encompassed topical and oral JAK inhibitors from five RCTs and three non‐RCTs, which led to increased heterogeneity 28 . As our research relied exclusively on data from 11 double‐blinded RCTs evaluating four oral JAK inhibitors, this approach confers several advantages, including (1) a more comprehensive analysis that enables a broader perspective on the treatment effects, (2) an increased statistical power that improves the precision of the estimated treatment effects and the reliability of our findings and (3) a broader inference which facilitates the assessment of consistency across the evidence.…”

Section: Discussionmentioning

confidence: 99%

Comparative efficacy of oral Janus kinase inhibitors and biologics in adult alopecia areata: A systematic review and Bayesian network meta‐analysis

Husein‐ElAhmed,

Husein‐ElAhmed

2024

Acad Dermatol Venereol

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Alopecia areata (AA) is an autoimmune disorder that affects the hair follicles, resulting in patchy recurrent hair loss. A large body of evidence has demonstrated the favourable clinical response of the Janus kinase (JAK) inhibitors and biologics, but a lack of comprehensive comparison among these therapies exists in the current literature. This study aimed to compare their efficacy. A systematic review and meta‐analysis were performed including randomized trials that report the outcomes of the Severity of Alopecia Tool (SALT)50 and/or the mean change in SALT. These articles were pooled and a network meta‐analysis (NAM) was conducted. Based on the surface under the cumulative ranking curve estimates obtained for the mean change in SALT score, baricitinib_4 mg (0.7949656) had the best probability of being the most effective therapy, followed by ritlecitinib_200_50 mg (0.7391906) and ivarmacitinib_4 mg (0.7292594). In contrast, dupilumab, secukinumab, tralokinumab and apremilast were less likely to be effective. Targeting the JAK signalling pathway holds great potential for restoring hair regrowth, albeit the contribution of JAK1, JAK2, JAK3 and TYK2 inhibition to the therapeutic effect on AA is apparently different. Baricitinib_4 mg and ritlecitinib 200_50 mg demonstrated notable efficacy, and both molecules displayed a dose‐dependent effect, which is not observed with ivarmacitinib. Further investigations into the specific mechanisms of action of these JAK inhibitors are warranted to elucidate the reasons behind these differences.

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“…Recent systematic reviews show that the safety profile of JAK inhibitors in alopecia areata in both adults 40,41 and children 42 is good.…”

Section: Therapeutic Managementmentioning

confidence: 99%

European expert consensus statement on the systemic treatment of alopecia areata

Rudnicka,

Arenbergerova,

Grimalt

et al. 2024

Acad Dermatol Venereol

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Alopecia areata is an autoimmune form of non‐scarring hair loss. It is usually characterized by limited areas of hair loss. However, the disease may progress to complete scalp and body hair loss (alopecia totalis, alopecia universalis). In patients with alopecia areata hair loss significantly impacts the quality of life. Children and adolescents with alopecia areata often experience bullying, including physical aggression. The disease severity evaluation tools used in clinical practice are: the Severity of Alopecia Tool (SALT) score and the Alopecia Areata Scale (AAS). A SALT score equal to or greater than 20 constitutes a commonly accepted indication for systemic therapy in alopecia areata. When using the AAS, moderate to severe alopecia areata should be considered a medical indication for systemic treatment. Currently, the only two EMA‐approved medications for alopecia areata are baricitinib (JAK 1/2 inhibitor) for adults and ritlecitinib (JAK 3/TEC inhibitor) for individuals aged 12 and older. Both are EMA‐approved for patients with severe alopecia areata. Other systemic medications used off‐label in alopecia areata include glucocorticosteroids, cyclosporine, methotrexate and azathioprine. Oral minoxidil is considered an adjuvant therapy with limited data confirming its possible efficacy. This consensus statement is to outline a systemic treatment algorithm for alopecia areata, indications for systemic treatment, available therapeutic options, their efficacy and safety, as well as the duration of the therapy.

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Efficacy and safety of different JAK inhibitors in the treatment of alopecia areata: a network meta-analysis

Cited by 11 publications

References 36 publications

Comparative efficacy and safety of JAK inhibitors in the treatment of moderate-to-severe alopecia areata: a systematic review and network meta-analysis

Comparative efficacy and safety of JAK inhibitors in the treatment of moderate-to-severe alopecia areata: a systematic review and network meta-analysis

Comparative efficacy of oral Janus kinase inhibitors and biologics in adult alopecia areata: A systematic review and Bayesian network meta‐analysis

European expert consensus statement on the systemic treatment of alopecia areata

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