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Journal of the American Academy of... Jan 2024
Topics: Humans; United States; Alopecia Areata; Incidence; Alopecia
PubMed: 37690704
DOI: 10.1016/j.jaad.2023.09.012 -
American Journal of Clinical Dermatology Mar 2024The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥... (Clinical Trial)
Clinical Trial
BACKGROUND
The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib, an oral JAK3/TEC family kinase inhibitor, is efficacious at doses of ≥ 30 mg in patients aged ≥ 12 years with alopecia areata (AA).
OBJECTIVE
The objective of this study was to evaluate the safety of ritlecitinib in an integrated analysis of four studies in AA.
METHODS
Two cohorts were analyzed: a placebo-controlled and an all-exposure cohort. Proportions and study size-adjusted incidence rates (IRs) of adverse events (AEs) of interest and laboratory abnormalities are reported.
RESULTS
In the placebo-controlled cohort (n = 881; median exposure: 169 days), the proportion of ritlecitinib-treated patients with AEs was 70.2-75.4% across doses versus 69.5% in the placebo group; serious AEs occurred in 0-3.2% versus 1.9% for the placebo. A total of 19 patients permanently discontinued due to AEs (5 while receiving the placebo). In the all-exposure cohort (n = 1294), median ritlecitinib exposure was 624 days [2091.7 total patient-years (PY)]. AEs were reported in 1094 patients (84.5%) and serious AEs in 57 (4.4%); 78 (6.0%) permanently discontinued due to AEs. The most common AEs were headache (17.7%; 11.9/100 PY), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (15.5%; 9.8/100 PY), and nasopharyngitis (12.4%; 8.2/100 PY). There were two deaths (breast cancer and acute respiratory failure/cardiorespiratory arrest). Proportions (IRs) were < 0.1% (0.05/100 PY) for opportunistic infections, 1.5% (0.9/100 PY) for herpes zoster, 0.5% (0.3/100 PY) for malignancies (excluding nonmelanoma skin cancer), and 0.2% (0.1/100 PY) for major adverse cardiovascular events.
CONCLUSIONS
Ritlecitinib is well tolerated with an acceptable safety profile up to 24 months in patients aged ≥ 12 years with AA (video abstract and graphical plain language summary available).
TRIAL REGISTRIES
ClinicalTrials.gov: NCT02974868 (date of registration: 11/29/2016), NCT04517864 (08/18/2020), NCT03732807 (11/07/2018), and NCT04006457 (07/05/2019).
Topics: Humans; Alopecia Areata; Antineoplastic Agents; Carbazoles; Janus Kinase 3; Protein Kinase Inhibitors; SARS-CoV-2; Treatment Outcome; Tryptamines
PubMed: 38263353
DOI: 10.1007/s40257-024-00846-3 -
Skin Appendage Disorders Oct 2023Alopecia areata (AA) is an autoimmune form of non-scarring hair loss that occurs on a spectrum from patchy loss of hair on the scalp, to complete hair loss. Histology... (Review)
Review
Alopecia areata (AA) is an autoimmune form of non-scarring hair loss that occurs on a spectrum from patchy loss of hair on the scalp, to complete hair loss. Histology features can vary, but increased abundance of telogen hair and miniaturized hair follicles are classic hallmarks [Clin Cosmet Investig Dermatol. 2015;8:397-403]. Additionally, lymphocytic infiltration of the hair bulb is a commonly observed histology feature of AA which underscores how the disease is an autoimmune-mediated one that results from immune-mediated attack of the hair follicle. In a healthy individual, the hair follicle is one of the body's immune-privileged sites, but the breakdown of this immune privilege is thought to be an important driver in AA disease development. Diagnosis of AA is usually based on phenotypic manifestations in conjunction with biopsies which can help conclude whether the hair loss is autoimmune based. However, varied manifestation of disease both clinically and histologically makes diagnosis criteria more ambiguous and early identification of disease harder to achieve. A better understanding of genes that are associated with increased AA risk may help elucidate potential gene targets for future therapeutics.
PubMed: 37900769
DOI: 10.1159/000530432 -
The Journal of Dermatology Feb 2024Alopecia areata (AA) affects individuals of all ages and is intractable in severe relapsing cases. Dermatologists and other healthcare providers should consider AA in... (Review)
Review
Alopecia areata (AA) affects individuals of all ages and is intractable in severe relapsing cases. Dermatologists and other healthcare providers should consider AA in the medical context and prioritize treatment. Several randomized controlled clinical studies on Janus kinase (JAK) inhibitors with different specificities for the treatment of AA are ongoing. These studies have encouraged us to appreciate the importance of a definitive diagnosis and accurate evaluation of AA before and during treatment. Following our previous review article in 2017, here we provide the second part of this two-review series on the recent progress in the multidisciplinary approaches to AA from more than 1800 articles published between July 2016 and December 2022. This review focuses on the evaluation, diagnosis, and treatment of AA. We also provide the latest information on the safety and efficacy of JAK inhibitors for the treatment of AA and describe their mechanisms of action.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Treatment Outcome
PubMed: 38087654
DOI: 10.1111/1346-8138.17064 -
Dermatology Practical & Conceptual Oct 2023Alopecia areata (AA) is a common, non-scarring, autoimmune hair loss disorder, varying in severity from small round hairless patches to the total loss of scalp or body... (Review)
Review
INTRODUCTION
Alopecia areata (AA) is a common, non-scarring, autoimmune hair loss disorder, varying in severity from small round hairless patches to the total loss of scalp or body hair. As steroid pulse therapy outcomes for AA vary, this study aimed to review the related literature regarding the efficacy, relapse rates, side effects, and prognostic factors associated with the response to different pulse corticosteroid treatments.
METHODS
We performed a literature search on August 29, 2022, to provide an overview of the efficacy of pulse steroid therapy in patients with AA. The terms "pulse steroid therapy AND alopecia areata" and "pulse corticosteroid therapy AND alopecia areata" were searched on PubMed and Google Scholar.
RESULTS
A total of 24 articles were assessed. There was no difference in outcomes and side effects between intravenous and oral pulse corticosteroid therapy. The relapse rate and efficacy depended on the time of AA onset, age, and AA type: improved outcomes and decreased relapse were linked with recent onset (<6 months), a younger age (<10 years), and the multifocal type of AA. Patients with a past medical history of atopy, nail pitting, or thyroid disease and those with severe forms of AA like alopecia totalis and alopecia universalis had the least improvement.
CONCLUSIONS
All kinds of mentioned systemic pulse corticosteroids effectively induce hair regrowth in AA. Betamethasone pulse seems to be the most effective agent (followed by intramuscular triamcinolone), especially in severe cases, but more side effects may accompany it. Combining this agent with other medications can reduce the dosage and side effects. Pulses of prednisolone and methylprednisolone are less effective but safer, as they have low relapse rates and adverse effects. A combination of them with other drugs can increase their efficacy.
PubMed: 37992355
DOI: 10.5826/dpc.1304a255 -
Immunotherapy Oct 2023This is a summary of the results of the ALLEGRO phase 2b/3 clinical trial, originally published in . ALLEGRO-2b/3 looked at how well and safely the study medicine,... (Review)
Review
WHAT IS THIS SUMMARY ABOUT?
This is a summary of the results of the ALLEGRO phase 2b/3 clinical trial, originally published in . ALLEGRO-2b/3 looked at how well and safely the study medicine, ritlecitinib, works in treating people with alopecia areata ('AA' for short). The immune system protects your body from outside invaders such as bacteria and viruses. AA is an autoimmune disease, meaning a disease in which one's immune system attacks healthy cells of the body by mistake. In AA, the immune system attacks hair follicles, causing hair to fall out. AA causes hair loss ranging from small bald patches to complete hair loss on the scalp, face, and/or body. Ritlecitinib is a medicine taken as a pill every day, by mouth, that is approved for the treatment of severe AA. It blocks processes that are known to play a role in causing hair loss in patients with AA.
WHAT WERE THE RESULTS OF THE STUDY?
Adults and adolescents (12 years and older) took part in the ALLEGRO-2b/3 study. They either took ritlecitinib for 48 weeks or took a placebo (a pill with no medicine) for 24 weeks. Participants taking placebo later switched to taking ritlecitinib for 24 weeks. The study showed that participants taking ritlecitinib had more hair regrowth on their scalp after 24 weeks than those taking the placebo. Hair regrowth was also seen on the eyebrows and eyelashes in participants taking ritlecitinib. Hair regrowth continued to improve to week 48 with continued ritlecitinib treatment. In addition, more participants taking ritlecitinib reported that their AA had 'moderately' or 'greatly' improved after 24 weeks than those taking the placebo. Similar numbers of participants taking ritlecitinib or placebo had side effects after 24 weeks. Most side effects were mild or moderate.
WHAT DO THE RESULTS OF THE STUDY MEAN?
Ritlecitinib was an effective and well-tolerated treatment over 48 weeks for people with AA. NCT03732807 (phase 2b/3 ALLEGRO study).
Topics: Humans; Adult; Adolescent; Alopecia Areata; Carbazoles; Tryptamines; Protein Kinase Inhibitors; Immunologic Factors
PubMed: 37403610
DOI: 10.2217/imt-2023-0069 -
Immunotherapy Aug 2023Atopic dermatitis is an inflammatory skin disease, the prevalence of which has increased in the last decade. It affects all age groups, with adult involvement being a... (Review)
Review
Atopic dermatitis is an inflammatory skin disease, the prevalence of which has increased in the last decade. It affects all age groups, with adult involvement being a major focus of interest in recent years. The unmet needs of the disease, such as pruritus, sleep quality impairment and eczematous skin lesions, have undergone a therapeutic revolution following the commercialization of drugs such as JAK inhibitors. Upadacitinib, a selective JAK1 inhibitor, has been positioned by both clinical trial results and those observed in clinical practice as the fastest and most effective drug in reducing both pruritus and Eczema Area and Severity Index and validated Investigator Global Assessment. Although the safety profile may be initially alarming, it is advisable to update the actual data in this regard for proper management. New perspectives for upadacitinib in nonatopic comorbidities such as psoriasis and alopecia areata are beginning to be described, and interest in learning more about its peculiarities is growing.
Topics: Adult; Humans; Dermatitis, Atopic; Heterocyclic Compounds, 3-Ring; Alopecia Areata; Janus Kinase Inhibitors; Pruritus
PubMed: 37194577
DOI: 10.2217/imt-2023-0037 -
Clinical, Cosmetic and Investigational... 2023Conflicting results have emerged in studies conducted to reveal the relationship between alopecia areata (AA) and depression and anxiety. The comorbidity of depression...
BACKGROUND
Conflicting results have emerged in studies conducted to reveal the relationship between alopecia areata (AA) and depression and anxiety. The comorbidity of depression and anxiety in patients with patchy AA who applied to a tertiary care center will be investigated and compared with a healthy control group.
METHODS
This study included 86 patients with AA and 85 healthy volunteers. The patients and controls completed Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BDI).
RESULTS
The average BDI of the patient group was 13.45±8.59, while in the control group, it was 7.2±5.7 ( = 0.002). The average BAI of the patient group was 12.56±8.76, while in the control group, it was 6.01±5.87 ( = 0.019). Depression was detected in 30.2% (n = 26) of the patients and anxiety was detected in 19.8% (n = 17) of the patients. In the control group, the rate of depression was 5.9% (n = 5) and the rate of anxiety was 7.1% (n = 6). There was a statistically significant difference between the patients and the control group in terms of depression ( < 0.001) and anxiety ( < 0.001).
CONCLUSION
Depression and anxiety were more prevalent in patients with AA than in healthy volunteers. Dermatologists should keep in mind psychiatric diseases such as depression and anxiety that may accompany patients diagnosed with AA.
PubMed: 37701059
DOI: 10.2147/CCID.S424374 -
Dermatology and Therapy Nov 2023Ritlecitinib demonstrated efficacy in patients with alopecia areata (AA) in the ALLEGRO phase 2b/3 study (NCT03732807). However, hair loss presentation may vary based on...
INTRODUCTION
Ritlecitinib demonstrated efficacy in patients with alopecia areata (AA) in the ALLEGRO phase 2b/3 study (NCT03732807). However, hair loss presentation may vary based on location (e.g., scalp, eyebrow/eyelash, body). Here, we sought to identify distinct hair loss profiles at baseline and evaluate whether they affected the efficacy of ritlecitinib.
METHODS
Patients with AA aged ≥ 12 years with ≥ 50% scalp hair loss were randomized to daily ritlecitinib 10 mg (assessed for dose ranging only), 30 or 50 mg (± 4-week, 200-mg loading dose), or placebo for 24 weeks. Latent class analysis (LCA) identified hair loss profiles based on four baseline measurements: clinician-reported extent of scalp (Severity of Alopecia Tool score), eyebrow hair loss, eyelash hair loss, and patient-reported body hair loss. Logistic regression evaluated ritlecitinib (50 and 30 mg) efficacy vs placebo using Patient Global Impression of Change (PGI-C) and Patient Satisfaction with Hair Growth (P-Sat; amount, quality, and overall satisfaction) responses at Week 24, adjusting for key covariates, including latent class membership.
RESULTS
LCA identified five latent classes: (1) primarily non-alopecia totalis (AT; complete loss of scalp hair); (2) non-AT with moderate non-scalp involvement; (3) extensive scalp, eyebrow, and eyelash involvement; (4) AT with moderate non-scalp involvement; and (5) primarily alopecia universalis (complete scalp, face, and body hair loss). Adjusting for latent class membership, patients receiving ritlecitinib 30 or 50 mg were significantly more likely to achieve PGI-C response (30 mg: odds ratio, 8.62 [95% confidence interval, 4.42-18.08]; 50 mg: 12.29 [6.29-25.85]) and P-Sat quality of hair regrowth (30 mg: 6.71 [3.53-13.51]; 50 mg: 8.17 [4.30-16.46]) vs placebo at Week 24. Results were similar for P-Sat overall satisfaction and amount of hair regrowth.
CONCLUSION
Distinct and clinically relevant hair loss profiles were identified in ALLEGRO-2b/3 participants. Ritlecitinib was efficacious compared with placebo, independent of hair loss profile at baseline.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, NCT03732807.
PubMed: 37707764
DOI: 10.1007/s13555-023-00997-x -
Health Science Reports Jul 2023Alopecia areata (AA) is a common autoimmune nonscarring hair disorder with strong genetic links. It seems to be associated with several comorbidities affecting the AA...
BACKGROUND AND AIMS
Alopecia areata (AA) is a common autoimmune nonscarring hair disorder with strong genetic links. It seems to be associated with several comorbidities affecting the AA treatment plan. On the other hand, the prevalence of comorbidities in different populations can be different based on genetic differences. This study aimed to clarify the association between age and sex with various comorbidities in AA patients.
METHODS
This cross-sectional study was conducted on 402 patients suffering from AA referred to our hospitals between 2018 and 2021. The clinical records of the patients were reviewed, including demographic and clinical information.
RESULTS
The most common diseases associated with AA were anxiety (36%), dermatitis (30%), hypothyroidism (9%), hyperlipidemia (5%), and vitamin D deficiency (4%). The most common comorbidities in AA patients over 18 years were allergic rhinitis, psychological problems, diabetes, hypertension, and hypothyroidism ( < 0.05). Hypothyroidism was more common in female patients than in male patients ( = 0.002). In contrast, hyperlipidemia was more common in male patients than in female patients ( = 0.024). There was a significant association between the severity of AA and hyperlipidemia and vitiligo ( = 0.003 and 0.045).
CONCLUSION
Sex and age could affect comorbidities. The prevalence of hypothyroidism was higher in our study; it was higher in women than in men. Thyroid function tests were recommended for AA patients.
PubMed: 37519427
DOI: 10.1002/hsr2.1444