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Secondary prevention of skin cancer consists in early detection of malignant lesions through patients' mole self-examination and medical examination. The objective of this study was to assess the self-reported frequency of mole examination in a large, representative sample of the adult general population of 17 countries from all continents. Of a total of 17,001 participants, 4.8% had their moles checked by a dermatologist more than once a year, 11.3% once a year, 8.4% every 2-3 years, 12.4% once in a while, 10.3% once in lifetime, and 52.6% of participants had never performed a mole examination. Egypt was the country with the highest prevalence of people who performed a moles check more than once a year (15.9%), followed by Brazil and the USA. A higher frequency of mole checks was associated with sex (man vs woman), higher education, higher income, fair phototype, history of skin cancer, medical insurance, and sun-protective behaviours. Despite recommendations by health providers, it appears that the frequency of mole checks in the general population is still low. It is necessary for dermatologists to keep informing at-risk populations about the importance of moles check, with particular care regarding categories that less frequently adhere to secondary prevention measures.
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Dermatologistas , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Dermatologistas/estatística & dados numéricos , Autoexame , Adulto Jovem , Idoso , Prevalência , Fatores de Risco , Nevo/epidemiologia , Nevo/diagnóstico , Prevenção Secundária , Saúde Global , Adolescente , Detecção Precoce de Câncer , Pesquisas sobre Atenção à Saúde , Fatores de Tempo , Valor Preditivo dos TestesRESUMO
Background: Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo. Methods: This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6 mg (UPA6), upadacitinib 11 mg (UPA11), upadacitinib 22 mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975. Findings: Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n = 49), UPA11 (n = 47), UPA22 (n = 43), or PBO (n = 46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was -7.60 (95% CI -22.18 to 6.97; p = 0.3037) for UPA6, -21.27 (95% CI -36.02 to -6.52; p = 0.0051) for UPA11, and -19.60 (95% CI -35.04 to -4.16; p = 0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was -7.45 (95% CI -16.86 to 1.96; p = 0.1198) for UPA6, -10.84 (95% CI -20.37 to -1.32; p = 0.0259) for UPA11 and -14.27 (95% CI -24.24 to -4.30; p = 0.0053) for UPA22. Ongoing treatment with upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n = 1)] and non-fatal ischemic stroke [UPA11 (n = 1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed. Interpretation: Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15 mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial. Funding: AbbVie Inc.
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BACKGROUND: Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden; representing a population with a clear unmet need for new treatments. OBJECTIVES: To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP), inadequately controlled by topical corticosteroids. METHODS: PRELUDE was a, randomised, double-blind, placebo-controlled, Phase 2 proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomised to eithersecukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W), or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤2 at Week 16. RESULTS: Overall, 111 patients were randomised (n=37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the 3 cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤2 response at Week 16 with SECQ4W vs. placebo in the MLP (37.5% [95% credibility interval (Crl): 20.3-57.2] vs. 23.1% [95% Crl: 6.5-49.2]) and LPP cohorts (37.5% [95% Crl: 20.2-57.3] vs. 30.8% [95% Crl: 10.8-57.6]). In the LPP cohort, a sustained response for IGA ≤2 from Week 16 to Week 32 was achieved with SECQ4W (Week 16: 37.5%; Week 32: 45.8%), and a substantial improvement was observed in IGA ≤2 response in patients of this cohort switching from placebo (Week 16: 30.8%) to SECQ2W after Week 16 (Week 32: 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals. CONCLUSIONS: PRELUDE is the first randomised controlled basket trial evaluating interleukin-17A inhibition with secukinumab across 3 subtypes of LP. Secukinumab was well-tolerated and safe, showing different response rates across the 3 subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of interleukin-17A across LP subtypes. The novel IGA score showed significant correlation with patient as well as physician reported outcome measurements. TRIAL REGISTRATION NUMBER: NCT04300296.
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The skin microbiome undergoes constant exposure to solar radiation (SR), with its effects on health well-documented. However, understanding SR's influence on host-associated skin commensals remains nascent. This review surveys existing knowledge on SR's impact on the skin microbiome and proposes innovative sun protection methods that safeguard both skin integrity and microbiome balance. A team of skin photodamage specialists conducted a comprehensive review of 122 articles sourced from PubMed and Research Gateway. Key terms included skin microbiome, photoprotection, photodamage, skin cancer, ultraviolet radiation, solar radiation, skin commensals, skin protection, and pre/probiotics. Experts offered insights into novel sun protection products designed not only to shield the skin but also to mitigate SR's effects on the skin microbiome. Existing literature on SR's influence on the skin microbiome is limited. SR exposure can alter microbiome composition, potentially leading to dysbiosis, compromised skin barrier function, and immune system activation. Current sun protection methods generally overlook microbiome considerations. Tailored sun protection products that prioritize both skin and microbiome health may offer enhanced defense against SR-induced skin conditions. By safeguarding both skin and microbiota, these specialized products could mitigate dysbiosis risks associated with SR exposure, bolstering skin defense mechanisms and reducing the likelihood of SR-mediated skin issues.
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BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with a substantial disease burden. Secukinumab has previously been reported to have sustained efficacy with a favourable safety profile in patients with moderate-to-severe HS. It is unknown whether prior biologic exposure affects the efficacy and safety of secukinumab. OBJECTIVES: To investigate the efficacy and safety of secukinumab in patients with moderate-to-severe HS based on prior exposure to -biologics. METHODS: This was an analysis of the SUNSHINE and SUNRISE phase III trials of secukinumab in patients with moderate-to-severe HS. Patients were randomized at baseline to receive secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W), or placebo for 16 weeks. After week 16, patients on the SECQ2W and SECQ4W schedules remained on the same treatment regimen, while patients randomized to placebo were switched to either SECQ2W or SECQ4W up to week 52. Assessments based on prior exposure to biologics included Hidradenitis Suppurativa Clinical Response (HiSCR), abscess and inflammatory nodule (AN) count, flare rates, HS-related pain [numerical rating scale 30 (NRS30)], 55% reduction in the International Hidradenitis Suppurativa Severity Score System (IHS4-55), Dermatology Life Quality Index, EuroQol-5D and safety. RESULTS: Overall, 1084 patients were randomized in the SUNSHINE and SUNRISE trials and included in this analysis; 255 (23.5%) were biologic-experienced [SECQ2W (n = 80); SECQ4W (n = 81); placebo (n = 94)] and 829 (76.5%) were biologic-naïve [SECQ2W (n = 281); SECQ4W (n = 279); placebo (n = 269)]. At week 16, responses were more efficacious for secukinumab than for placebo with regard to HiSCR in patients who were biologic-experienced {SECQ2W 37.0% [odds ratio (OR) 1.60, 95% confidence interval (CI) 0.83-3.08]; SECQ4W 38.8% [OR 1.67, 95% CI 0.86-3.22]; placebo 27.3%} and biologic-naïve [SECQ2W 45.6% (OR 1.64, 95% CI 1.15-2.33); SECQ4W 45.4% (OR 1.61, 95% CI 1.13-2.29); placebo 34.2%]. Similar results were observed for AN count, NRS30 and IHS4-55. The higher response seen at week 16 with secukinumab was sustained, with a trend toward improvement over time, through to week 52 in both subgroups. Additional efficacy was observed for quality-of-life assessments, and no differences in safety between subgroups were observed. CONCLUSIONS: Regardless of prior biologic exposure, secukinumab was efficacious in improving the signs and symptoms of HS. This finding positions secukinumab as the first option in patients who are biologic-naïve, as well as in patients who have previously been treated with other biologic therapy, based on individual patient needs.
Hidradenitis suppurativa (HS) is a chronic skin disease that causes painful boils. HS is common and affects about 0.4% of the world's population. Treating the condition is difficult, but drugs called 'biologics' can help to improve the symptoms. For example, secukinumab is a biologic drug that has been shown to be effective and well-tolerated for the treatment of HS. In this analysis, we investigated whether previous treatment with biologics could affect the effectiveness and tolerability of secukinumab. This analysis included data from two identical clinical trials (called SUNSHINE and SUNRISE) that recruited adult patients with HS who had moderate-to-severe disease. In these trials, patients took secukinumab 300â mg every 2 weeks or every 4 weeks for 1â year, or a placebo for 4â months and then switched to secukinumab until 1â year. At regular intervals, the effectiveness and tolerability of secukinumab were examined and the results were compared between patients who had previously used another biologic and patients who had never used a biologic before. After 16 weeks, patients who took secukinumab had better results than the patients who took a placebo, independent of previous biologic use. Secukinumab was still effective and had improved results over 1â year of treatment in both subgroups. Regardless of whether patients had previously been taking another biologic, secukinumab was just as tolerable as placebo and there were no new safety risks. Our analysis shows that secukinumab is effective and tolerable, regardless of whether patients have previously used another biologic drug.
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Anticorpos Monoclonais Humanizados , Fármacos Dermatológicos , Hidradenite Supurativa , Humanos , Hidradenite Supurativa/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Feminino , Adulto , Resultado do Tratamento , Pessoa de Meia-Idade , Método Duplo-Cego , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Esquema de MedicaçãoRESUMO
INTRODUCTION: Hyperpigmentation disorders are very frequent, affect the quality of life and may become a psychological burden for afflicted patients. Many anti-pigmenting or depigmenting agents are available with various efficacy and almost no comparative data. 2-mercaptonicotinoyl glycine (2-MNG) was recently proposed as a viable candidate showing safe and effective results on hyperpigmentation control in vitro and in vivo. OBJECTIVES: A Bayesian network meta-analysis (BNMA) was conducted to map and rank the anti-pigmenting and depigmenting efficacy of 2-MNG 0.5% on UV daylight (UVDL)-induced pigmentation together with 13 other reference molecules. A comparison in the kinetics of 2-MNG 0.5% was also performed. METHODOLOGY: Fourteen studies were conducted, for each, on 15-30 women of skin phototype III in Shanghai, China and Paris, France. The products were applied on mini zone, in randomized and blinded protocol, on the back, 5 days a week during 6 weeks, at a dose of 4 mg/cm2. During the second week, volunteers were exposed under to varying minimum erythemal dose of UVDL during 4 consecutive days-adapted to obtain a similar induction of skin pigmentation regardless of the population. Assessments were performed instrumentally using Chromameter®. Ascorbic acid 7% was used as a positive control for all experiments. A Bayesian network meta-analysis was then established to map and follow the kinetics of 2-MNG 0.5% performance with 13 reference molecules (glutathione 2%, kojic acid 1%, hydroquinone 4%, ascorbyl glucoside 2%, niacinamide 4%, etc.). RESULTS: 2-MNG 0.5% dominated the ranking at all time points with a significant high probability of strong efficacy against UVDL-induced pigmentation. Ascorbic acid 7% ranks second after 4 days of irradiations (D12) whereas hydroquinone 4% ranks second 1 month after irradiations (D40). In the kinetics, 2-MNG at 0.5% was effective as from the end of irradiations (D12) to the study endpoint (D40). This suggested an immediate and persistent efficacy across all timepoints evaluated. CONCLUSION: The BNMA revealed a rapid and lasting efficacy of 2-MNG 0.5% on the anti-pigmenting and depigmenting phases of the clinical protocol. 2-MNG 0.5% ranked first, with immediate and lasting effect compared to 13 other references. This study is the first allowing comparison between reference anti-pigmenting and depigmenting agents and will help clinicians for proposing the most effective approach for their patients.
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Teorema de Bayes , Hiperpigmentação , Raios Ultravioleta , Humanos , Raios Ultravioleta/efeitos adversos , Hiperpigmentação/prevenção & controle , Metanálise em Rede , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos da radiação , FemininoRESUMO
BACKGROUND: In the phase III POETYK PSO-1 and PSO-2 trials, deucravacitinib, an oral selective allosteric tyrosine kinase 2 inhibitor, was well tolerated and efficacious over 1â year in patients with psoriasis. OBJECTIVE: To evaluate deucravacitinib safety and efficacy over 2â years in patients participating in the phase III trials. METHODS: In the POETYK long-term extension (LTE), an ongoing phase IIIb open-label trial, adults with moderate-to-severe plaque psoriasis who completed PSO-1 or PSO-2 receive deucravacitinib 6â mg once daily. Safety was assessed via adverse events (AEs) and laboratory parameter abnormalities. Efficacy endpoints, including ≥ 75% reduction from baseline Psoriasis Area and Severity Index score (PASI 75) and static Physician's Global Assessment (sPGA) score of 0/1 (clear/almost clear), were evaluated in patients originally randomized to deucravacitinib, patients who crossed over from placebo at week 16 and patients who achieved PASI 75 at week 24 (peak efficacy). RESULTS: At data cutoff (1 October 2021), 1519 patients had received at least one dose of deucravacitinib; 79.0% and 39.9% had ≥ 52 weeks and ≥ 104 weeks of total deucravacitinib exposure, respectively. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were similar at 1â year and 2â years for any AEs (229.2 vs. 154.4, respectively), serious AEs (5.7 vs. 6.1), discontinuations (4.4 vs. 2.8), deaths (0.2 vs. 0.4), serious infections (1.7 vs. 2.6), herpes zoster (0.9 vs. 0.8), major adverse cardiovascular events (0.3 vs. 0.4), venous thromboembolic events (0.2 vs. 0.1) and malignancies (1.0 vs. 0.9). EAIRs for COVID-19 infections were higher at 2â years than at 1â year (5.1 vs. 0.5) owing to the peak of the global COVID-19 pandemic occurring during the LTE. No clinically meaningful changes from baseline or trends were observed over 2â years in haematological, chemistry or lipid parameters. Clinical responses were maintained in patients who received continuous deu-cravacitinib treatment from baseline [PASI 75: week 52, 72.4%; week 112, 79.7%; sPGA 0/1: week 52, 57.9%; week 112, 61.1% (as observed)]. Responses at week 52 were also maintained in placebo crossovers and in week-24 PASI-75 responders. CONCLUSIONS: Deucravacitinib maintained efficacy and demonstrated consistent safety with no new safety signals observed through 2â years.
Psoriasis is a chronic inflammatory skin condition. Many available treatments for psoriasis are injected, but can be inadequate in terms of effectiveness, and/or cause serious side-effects. Deucravacitinib is a recently approved oral medicine that interferes with an enzyme involved in inflammation called 'tyrosine kinase 2' (TYK2). Deucravacitinib has been shown to improve psoriatic patches and symptoms (such as itching) through 1â year in two global clinical trials in adults with moderate-to-severe plaque psoriasis (POETYK PSO-1 and PSO-2). This study was an analysis of the safety and efficacy of deucravacitinib for up to 2â years. To do this, the researchers used data from approximately 1500 people who completed both trials and continued into an ongoing, long-term extension trial (POETYK LTE). Overall, there were no new side-effects, and the number, type and severity of side-effects, as well as the number of patients who stopped treatment because of these side-effects, remained low. The most frequent side-effects included common cold symptoms and COVID-19. Rates of shingles and serious side-effects were comparable to rates reported in the real world. Improvements in psoriasis symptoms seen at 1â year were maintained for up to 2â years in patients receiving deucravacitinib treatment from the start of PSO-1 or PSO-2, or who crossed over from placebo to deucravacitinib at 4â months. Long-term treatment with deucravacitinib improved psoriasis symptoms and resulted in mostly mild side-effects. The study findings suggest that deucravacitinib could be a well-tolerated and effective treatment for people with psoriasis.
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Compostos Heterocíclicos , Pandemias , Psoríase , Adulto , Humanos , Índice de Gravidade de Doença , Psoríase/tratamento farmacológico , Resultado do Tratamento , Método Duplo-CegoRESUMO
This case report describes a woman in her 20s who presented with an itchy erythematous-papulo-pustular eruption of the scalp for 3 months with progressive centrifugal extension to the face and was diagnosed with Ofuji disease.
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Anticorpos Monoclonais Humanizados , Eosinofilia , Foliculite , Dermatopatias Vesiculobolhosas , Humanos , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Foliculite/diagnóstico , Foliculite/tratamento farmacológico , Dermatopatias Vesiculobolhosas/diagnóstico , Dermatopatias Vesiculobolhosas/tratamento farmacológicoRESUMO
Importance: Palmoplantar pustulosis (PPP) and palmoplantar plaque psoriasis with pustules remain challenging to treat. Studies suggest that an interleukin 17 or interleukin 36 loop acts synergistically in these diseases to induce palmoplantar pustules. Objective: To assess the effectiveness of bimekizumab in treating PPP and palmoplantar plaque psoriasis with pustules. Design, Setting, and Participants: This case series involved 21 adults with PPP (11 patients) or palmoplantar plaque psoriasis with pustules (10 patients) treated at 1 of 7 tertiary dermatological centers in France from September 2022 through June 2023. All patients treated with bimekizumab for at least 3 months were included in the analyses. Main Outcomes and Measures: The main outcome was the posttreatment Investigator Global Assessment (IGA), scored as 0 (complete clearance), 1 (almost clear), 2 (mild), 3 (moderate), or 4 (severe). When relevant, evolution of joint pain and nail involvement was reported. Tolerance and potential adverse events were noted. Results: A total of 21 patients (mean [range] age, 46 [24-68] years; 19 females) were included. Eleven patients had isolated PPP, and 10 had palmoplantar plaque psoriasis with pustules. All of them, except 2 who received bimekizumab as first systemic therapy, had not responded to at least 1 systemic treatment (median [range], 3 [1-7] treatments), and/or had adverse events leading to the discontinuation of the treatment. Complete clearance (IGA score, 0) was achieved by 17 patients in 1 to 4 months. Three patients achieved an IGA score of 1, and 1 achieved an IGA score of 2. Three patients with PPP also presented with acrodermatitis continua of Hallopeau. Nail involvement showed 50% to 70% improvement after 4 to 6 months of bimekizumab treatment for these 3 patients. Two patients had SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome; both had complete clearance of skin lesions associated with joint pain improvement. Four patients (19%) with candidiasis were successfully treated with oral antifungal agents. None of the patients had to stop bimekizumab treatment due to adverse events. Conclusions and Relevance: The findings of this case series suggest that bimekizumab could be an appealing approach for treating PPP, palmoplantar plaque psoriasis with pustules, and SAPHO syndrome. Prospective randomized placebo-controlled clinical trials are needed to confirm these encouraging initial results.
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Anticorpos Monoclonais Humanizados , Psoríase , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Psoríase/patologia , Artralgia , Imunoglobulina ARESUMO
Alopecia areata (AA) is an autoimmune disease that has a complex underlying immunopathogenesis characterized by nonscarring hair loss ranging from small bald patches to complete loss of scalp, face, and/or body hair. Although the etiopathogenesis of AA has not yet been fully characterized, immune privilege collapse at the hair follicle (HF) followed by T-cell receptor recognition of exposed HF autoantigens by autoreactive cytotoxic CD8+ T cells is now understood to play a central role. Few treatment options are available, with the Janus kinase (JAK) 1/2 inhibitor baricitinib (2022) and the selective JAK3/tyrosine kinase expressed in hepatocellular carcinoma (TEC) inhibitor ritlecitinib (2023) being the only US Food and Drug Administration-approved systemic medications thus far for severe AA. Several other treatments are used off-label with limited efficacy and/or suboptimal safety and tolerability. With an increased understanding of the T-cell-mediated autoimmune and inflammatory pathogenesis of AA, additional therapeutic pathways beyond JAK inhibition are currently under investigation for the development of AA therapies. This narrative review presents a detailed overview about the role of T cells and T-cell-signaling pathways in the pathogenesis of AA, with a focus on those pathways targeted by drugs in clinical development for the treatment of AA. A detailed summary of new drugs targeting these pathways with expert commentary on future directions for AA drug development and the importance of targeting multiple T-cell-signaling pathways is also provided in this review.