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Alopecia areata

GtoPdb Disease Summaries

This section gives an overview of the disease, and where available shows the following:

  • Synonyms: Shows known synonyms for the disease.
  • Description: Gives a basic description/definition of the disease.
  • Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
  • Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
  • Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

More information can be found in the help pages.

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Disease ID:1200
Name:Alopecia areata
Associated with:0 target
3 immuno-relevant ligands
Synonyms
circumscribed alopecia
Description
A hypersensitivity reaction type II disease causing loss of head and body hair, initially causing bald spots.
Database Links
Disease Ontology: DOID:986

Targets

GtoPdb Disease Summaries - Targets

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Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.

If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page

Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

More information can be found in the help pages.

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Key to terms and symbols

No target related data available for Alopecia areata

Ligands

GtoPdb Disease Summaries - Ligands

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  • Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
  • Immuno: Immuno icon indicates the ligand is immuno-relevant

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  • Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
  • Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
  • Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.

More information can be found in the help pages.

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Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
tralokinumab
Immuno Disease Comments: Phase 2 clinical candidate for alopecia areata (see NCT02684097).
Clinical Use: Tralokinumab reached Phase 3 clinical trials for uncontrolled asthma, and atopic dermatitis, and Phase 2 for alopecia areata. Click here to link to ClinicalTrials.gov's listing of Phase 3 tralokinumab trials. In addition, Phase 2 trials are investigating tralokinumab as a treatment for idiopathic pulmonary fibrosis (IPF, NCT01629667 and NCT02036580). Business reports online indicate that AstraZeneca have discontinued tralokinumab development foa asthma as it showed no benefit over placebo in their STRATOS 2 and TROPOS late-stage asthma trials [1].
The EMA approved LEO Pharma's tralokinumab product Adtralza® in July 2021, as a treatment for severe atopic dermatitis that cannot be controlled by topical drugs. FDA approval for this indication followed at the end of 2021. | View clinical data
baricitinib
Immuno Disease Comments: Baricitinib is approved by the FDA as a treatment for severe alopecia areata
Clinical Use: The EMA granted baricitinib marketing authorisation in February 2017, for the treatment of rheumatoid arthritis (RA). This approval covered doses of either 2 or 4 mg. Phase 3 trial results reporting significant clinical improvement in patients who's symptoms had failed to respond to other disease-modifying antirheumatic drugs (DMARDs) were published in [3]. These are the results of the RA-BEACON study NCT01721044. FDA approval, as a once daily treatment for moderately-to-severely active RA, in patients with an inadequate response to one or more tumour necrosis factor (TNF) inhibitor therapies, was granted in June 2018, but only for the 2 mg dose. In both jurisdictions, baricitinib can be used as monotherapy, or in combination with or other non-biologic DMARDs. Use of baricitinib in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as and is not recommended.
Baricitinib was approved by the FDA as the first systemic, once-daily therapy for severe alopecia areata in June 2022.

SARS-CoV-2 and COVID-19: In November 2020, the FDA granted the combination of baricitinib + emergency use authorisation (EUA) as a treatment option for hospitalised COVID-19 patients, based on data from the ACTT-2 study (NCT04401579).

Most recently (late 2023), baricitinib has been shown to preserve β-cell function in patients with new-onset Type 1 diabetes [10]. | View clinical data
Bioactivity Comments: Preclinical studies of baricitinib have shown it to be effective in rat models of rheumatoid arthritis [2].
A single patient with alopecia areata (AA) with comorbid CANDLE syndrome (a immunoproteasome-related disorder with a prominent interferon (IFN) signature, a disease feature shared with AA), recruited to a clinical trial testing baricitinib as a treatment for their CANDLE syndrome (NCT01724580) experienced significant hair regrowth [4]. Mechanistic assessment in a mouse AA model, confirmed that clinical improvement correlated with baricitinib-induced resolution of the IFN signature. Other JAK inhibitors such as and have also been reported to promote hair regrowth in AA in early stage trials [5,8,11]. | View biological activity
ritlecitinib 6
Immuno Disease Comments: Phase 2b/3 clinical candidate for AA (NCT03732807). In August 2021, Pfizer announced that ritlecitinib had met its primary endpoint (reduction in hair loss) in this study. Results from phase 2a NCT02974868 comparing ritlecitinib and brepocitinib with placebo at 24 weeks were published by King et al. (2021).
Clinical Use: PF-06651600 completed Phase 2 clinical trials for rheumatoid arthritis and ulcerative colitis and was advanced to Phase 2b/3 in alopecia areata patients (the ALLEGRO study). Click here to link to ClinicalTrials.gov's full list of PF-06651600 trials. In June 2023 the FDA approved ritlecitinib to treat severe alopecia areata, based on positive efficacy results from the ALLEGRO study [7]. The UK's HMRA approved the drug for this indication in November 2023. | View clinical data
Bioactivity Comments: PF-06651600 exhibits favourable selectivity against a screening panel of 305 kinases in vitro, and shows measurable inhibition of 7 of the 10 other kinases which share a cysteine residue analogous to Cys-909 in the JAK3 ATP binding site (these were BMX, ITK, TXK, TEC, BTK, BLK and HER4) [9].
ATP concentration for JAK3 is 4 μM at Km and for JAK1 is 40 μM at Km, but some assays reported in [9] were carried out at 1 mM ATP . | View biological activity

References

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1. Adams B. Sanofi ditches IL-4/IL-13 antibody drug in lung-scarring disease. Accessed on 09/02/2018. Modified on 09/02/2018. fiercebiotech.com, https://www.fiercebiotech.com/biotech/sanofi-ditches-il4-il13-antibody-drug-lung-scarring-disease

2. Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, Favata MF et al.. (2010) Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol, 184 (9): 5298-307. [PMID:20363976]

3. Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, Beattie SD, Koch AE, Cardillo TE, Rooney TP et al.. (2016) Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med, 374 (13): 1243-52. [PMID:27028914]

4. Jabbari A, Dai Z, Xing L, Cerise JE, Ramot Y, Berkun Y, Sanchez GA, Goldbach-Mansky R, Christiano AM, Clynes R et al.. (2015) Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib. EBioMedicine, 2 (4): 351-5. [PMID:26137574]

5. Kennedy Crispin M, Ko JM, Craiglow BG, Li S, Shankar G, Urban JR, Chen JC, Cerise JE, Jabbari A, Winge MC et al.. (2016) Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight, 1 (15): e89776. [PMID:27699252]

6. King B, Guttman-Yassky E, Peeva E, Banerjee A, Sinclair R, Pavel AB, Zhu L, Cox LA, Craiglow B, Chen L et al.. (2021) A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results. J Am Acad Dermatol, 85 (2): 379-387. [PMID:33757798]

7. King B, Zhang X, Harcha WG, Szepietowski JC, Shapiro J, Lynde C, Mesinkovska NA, Zwillich SH, Napatalung L, Wajsbrot D et al.. (2023) Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial. Lancet, 401 (10387): 1518-1529. [PMID:37062298]

8. Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G, Furniss M, Vaughan R, Christiano AM, Clynes R. (2016) Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight, 1 (15): e89790. [PMID:27699253]

9. Thorarensen A, Dowty ME, Banker ME, Juba B, Jussif J, Lin T, Vincent F, Czerwinski RM, Casimiro-Garcia A, Unwalla R et al.. (2017) Design of a Janus Kinase 3 (JAK3) Specific Inhibitor 1-((2S,5R)-5-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) Allowing for the Interrogation of JAK3 Signaling in Humans. J Med Chem, 60 (5): 1971-1993. [PMID:28139931]

10. Waibel M, Wentworth JM, So M, Couper JJ, Cameron FJ, MacIsaac RJ, Atlas G, Gorelik A, Litwak S, Sanz-Villanueva L et al.. (2023) Baricitinib and β-Cell Function in Patients with New-Onset Type 1 Diabetes. N Engl J Med, 389 (23): 2140-2150. [PMID:38055252]

11. Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, de Jong A, Harel S, DeStefano GM, Rothman L et al.. (2014) Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med, 20 (9): 1043-9. [PMID:25129481]