Psoriasis

Disease ID:801
Name:Psoriasis
Associated with:4 targets
2 immuno-relevant targets
54 immuno-relevant ligands
Description
A long-term autoimmune disease characterized by patches of red, itchy, and scaly skin. Five types of psoriasis are recognised: plaque (psoriasis vulgari), guttate, inverse, pustular, and erythrodermic, with plaque psoriasis being the most common type.
Database Links
Disease Ontology: DOID:8893

Targets

C5a1 receptor
Role:  Evidence of a role for C5aR in psoriasis stems from the observation that the ligands for C5aR, C5a/C5a-des-arg, are the most abundant cytokine isolated from human psoriatic scales.
References:  2,24
CD2
Comments:  CD2 is the molecular target of alefacept, a drug that was approved for the treatment of moderate to severe plaque psoriasis.
Ligand interactions
Ligand Name Disease Association Comments Approved Primary Target Immuno
alefacept
Approved drug for plaque psoriasis (no longer authorised for use in some countries).
 [  (Drugs.com) ]
CD6
Comments:  CD6 is the molecular target of itolizumab, a drug approved for the treatment of chronic plaque psoriasis.
Ligand interactions
Ligand Name Disease Association Comments Approved Primary Target Immuno
itolizumab
Approved drug for chronic plaque psoriasis.
 [  (Drugs.com) ]

Ligands

Ligand Approved Immuno References Clinical comments
doramapimod
Clinical Use: Doramapimod (as research code BIRB 796) has been assessed in Phase II clinical trials for plaque-type psoriasis and rheumatoid arthritis (RA). Additional trials for RA and Crohn's disease were terminated. Development of the compound has not progressed beyond Phase II.
Immuno Disease Comments: Phase 2 clinical candidate for psoriasis.
CXCL11 15
Immuno Disease Comments: CXCL11 (and CCL5) expression is increased in lesional compared with nonlesional psoriatic skin, and levels correlate with levels of IFNγ in the skin samples.
guselkumab  [  (Drugs.com) ]
Clinical Use: Having completed Phase III clinical trials for various forms of psoriasis, guselkumab was approved in 2017 for patients with moderate to severe plaque psoriasis. Click here to link to ClinicalTrials.gov's listing of Phase III guselkumab trials.
Immuno Disease Comments: First anti-IL-23 biologic therapy to be approved. Approved for the treatment of moderate to severe plaque psoriasis, in patients considered as candidates for systemic therapy or phototherapy.
mirikizumab
Clinical Use: Phase 2 clinical trials which will evaluate mirikizumab (as research code LY3074828) in Crohn's disease (NCT02891226), ulcerative colitis (NCT02589665) and plaque psoriasis (NCT02899988) patients are underway.
Immuno Disease Comments: Phase 2 clinical candidate for moderate to severe plaque type psoriasis- see NCT02899988.
piclidenoson
Clinical Use: Piclidenoson (CF101) is being evaluated in a number of clinical trials, as a potential therapy for several autoimmune-inflammatory disorders (rheumatoid arthritis, Phase III, NCT02647762 [29]; plaque psoriasis, Phase II [4]; uveitis Phase II) and glaucoma (Phase II, NCT01033422 [8]).
Immuno Disease Comments: Clinical candidate for plaque psoriasis (Phase 2 NCT00428974).
GSK2981278 27
Clinical Use: GSK2981278 has completed Phase clinical trial (NCT03004846) in patients with plaque psoriasis.
Immuno Disease Comments: Phase 2 clinical candidate for plaque type psoriasis (see NCT03004846).
tapinarof
Clinical Use: Topically applied tapinarof (research code GSK2894512) has shown clinical efficacy in Phase 2 clinical trial in patients with plaque psoriasis [3] (NCT02564042). A Phase 3 trial (NCT03202004) is ready to recruit subjects (Oct 2017). Tapinarof has also completed Phase 1 studies for atopic dermatitis.
Immuno Disease Comments: Phase 3 clinical candidate for plaque psoriasis- NCT03202004.
CEP-37440
Clinical Use: CEP-37440 has completed Phase 1 clinical trial as an oncology candidate (see NCT01922752).
Immuno Disease Comments: Phase 2 clinical candidate for moderate-severe psoriasis- see NCT02931838
seletalisib 12
Clinical Use: First-in-human results were reported by Helmer et al. (2017) [12]. This article reports data from clinical trials NCT02303509 (safety and tolerability in healthy and psoriatic subjects) and NCT02207595 (safety and tolerability in healthy subjects only). A proof of concept Phase 2 trial in patients with primary Sjögren's syndrome has been terminated due to difficulty in enrolling suitable patient numbers (NCT02610543).
Immuno Disease Comments: Phase 1 clinical candidate for psoriasis- see NCT02303509
brodalumab  [  (Drugs.com) ]
Clinical Use: Brodalumab was first approved in Japan (2016), and by the US FDA for plaque psoriasis the following year. Regulatory decisions are pending elsewhere. Clinical trials for the treatment of psoriatic arthritis (Phase III), moderate to severe plaque psoriasis (Phase III) and asthma (Phase II) are ongoing. Encouraging results from a Phase II study have been reported [22].
Immuno Disease Comments: Approved therapeutic for plaque psoriasis.
MK-0873
Clinical Use: MK-0873 has completed Phase 2 clinical evaluation in rheumatoid arthritis (NCT00132769), and Phase 1 as a topical agent for plaque psoriasis (NCT01235728). A Phase 2 trial in patients with chronic obstructive pulmonary disease (COPD) was terminated (NCT00132730).
Immuno Disease Comments: Completed Phase 2 trial for plaque psoriasis- see NCT01140061
CCL2
Immuno Disease Comments: CCL2 is implicated in the pathogenesis of psoriasis.
cortisol  [  (Drugs.com) ]
Clinical Use: Hydrocortisone is used to treat many immune and allergic disorders, adrenal insufficiency disorders (eg Addison's disease) and corticosteroid-responsive dermatological disorders (eg psoriasis, atopic dermatitis, and contact dermatitis).
Immuno Disease Comments: Glucocorticoid drug used to treat many inflammatory condtions including psoriasis.
triamcinolone  [  (Drugs.com) ]
Clinical Use: Triamcinolone is used for its antiinflammatory or immunosuppressive actions in many conditions. For example, oral triamcinolone is used to treat conditions such as allergic disorders, skin conditions, ulcerative colitis, arthritis, lupus, psoriasis, and breathing disorders. This drug is also used topically as an anti-inflammatory and anti-pruritic agent. Injectable forms of the drug may be used to reduce intra-articular joint pain, stiffness and swelling associated with rheumatoid and osteoarthritic arthritis, bursitis, epicondylitis, and tenosynovitis.
Immuno Disease Comments: Glucocorticoid drug used to treat many inflammatory condtions including psoriasis.
ACTH  [  (Drugs.com) ]
Clinical Use: Corticotropin is used to treat the symptoms of many allergic disorders, psoriasis and other skin conditions, eye conditions, arthritis, lupus, multiple sclerosis, ulcerative colitis and breathing disorders, for example. This peptide is also used to diagonse adrenocortical insufficiency.
Immuno Disease Comments: A corticotropin used to treat the symptoms of many inflammatory disorders including psoriasis.
adalimumab  [  (Drugs.com) ]
Clinical Use: Used in the management of rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease and plaque psoriasis.
In 2015 both the EMA and the FDA approved the use of adalimumab as a treatment for hidradenitis suppurativa, a chronic skin disease that causes abscesses and scarring on the skin.
In July 2016, the FDA expanded adalimumab approval as the first non-corticosteroid drug available for use as a treatment for non-infectious intermediate, posterior and panuveitis (forms of autoimmune-driven inflammation of the uvea)- results from Phase 3 clinical trial NCT01138657 are published in [13].
Immuno Disease Comments: Anti-TNFα monoclonal antibody therapy approved for psoriatic arthritis and plaque psoriasis.
IL-17A
Immuno Disease Comments: Approved therapy for psoriasis.
methimazole  [  (Drugs.com) ]
Clinical Use: Used in the treatment of hyperthyroidism, goiter, Graves disease and psoriasis.
Immuno Disease Comments: Approved drug for psoriasis.
golimumab  [  (Drugs.com) ]
Clinical Use: Used in adults with various inflammatory conditions [31] e.g. moderate to severe active rheumatoid arthritis [16], active psoriatic arthritis, active ankylosing spondylitis and moderate to severe ulcerative colitis.
Immuno Disease Comments: An anti-TNFα therapy approved for psoriasis.
alefacept  [  (Drugs.com) ]
Clinical Use: This drug was approved for the treatment of inflammation in moderate to severe psoriasis with plaque formation. Use of alefacept has since been discontinued in the US.
Immuno Disease Comments: Approved drug for plaque psoriasis (no longer authorised for use in some countries).
efalizumab  [  (Drugs.com) ]
Clinical Use: Used to treat psoriasis prior to withdrawl from the market.
Immuno Disease Comments: Approved drug for psoriasis which was later withdrawn from the market.
etanercept  [  (Drugs.com) ]
Clinical Use: Used to treat severe active rheumatoid arthritis in adults, severe juvenile idiopathic arthritis, ankylosing spondylitis, and severe plaque psoriasis.
Immuno Disease Comments: Approved drug for severe plaque psoriasis.
ustekinumab  [  (Drugs.com) ]
Clinical Use: Used to treat adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and is approved in the US to treat psoriatic arthritis.
Immuno Disease Comments: An anti-IL-12B therapy approved to treat psoriasis.
amcinonide  [  (Drugs.com) ]
Clinical Use: Used to treat itching and inflammation associated with allergic and other inflammatory skin conditions.
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
betamethasone  [  (Drugs.com) ]
Clinical Use: Betamethasone is a synthetic glucocorticoid receptor (GR) agonist, with anti-inflammatory, antipruritic, and vasoconstrictive activities. The drug is used to treat the inflammatory sympotoms of conditions including atopic, seborrhoeic, and contact dermatitis, psoriasis and insect bite reactions.
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
clobetasol propionate  [  (Drugs.com) ]
Clinical Use: Used to treat skin inflammation and itching caused by conditions such as allergic reactions, eczema, and psoriasis.
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
desonide  [  (Drugs.com) ]
Clinical Use: Used to reduce skin inflammation caused by allergic reactions, eczema and psoriasis.
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
desoximetasone  [  (Drugs.com) ]
Clinical Use: Used to reduce skin inflammation caused by allergic reactions, eczema and psoriasis.
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
diflorasone diacetate  [  (Drugs.com) ]
Clinical Use: Used to reduce skin inflammation caused by allergic reactions, eczema and psoriasis.
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
flumethasone pivalate  [  (Drugs.com) ]
Clinical Use: Used to reduce skin inflammation caused by allergic reactions, eczema and psoriasis. However, there is no information regarding approval for clinical use of this drug on the US FDA website. Other national approval agencies may have granted marketing authorisation.
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
ixekizumab  [  (Drugs.com) ]
Clinical Use: Ixekizumab is approved for the treatment of psoriasis. Positive results from a Phase 2 study are reported in [9], and Phase 3 results are reviewed in [7]. In March 2016, the US FDA approved ixekizumab for the treatment of moderate-to-severe plaque psoriasis. The EMA granted marketing authorisation in April 2016.
Phase 3 results following 60 weeks of treatment are reported in [10], showing longer term efficacy (with ~80% of patients seeing at least a 75% improvement in their skin symptoms at 60 weeks).
Immuno Disease Comments: Approved therapeutic for psoriasis and plaque psoriasis.
prednicarbate  [  (Drugs.com) ]
Clinical Use: Prednicarbate is a topical corticosteroid drug [11]. It is used to relieve inflammatory and pruritic symptoms of corticosteroid-responsive skin conditions such as seborrheic or atopic dermatitis, localized neurodermatitis, psoriasis, the late phase of allergic contact dermatitis and the inflammatory phase of xerosis cutis. Prednicarbate is claimed to have low atrophogenic potential compared to other glucocorticoids [17-18].
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat psoriasis.
E6201
Clinical Use: E6201 has been assessed in the completed clinical trial NCT01268527, for the treatment of psoriasis vulgaris. There are no further ongoing trials registered with ClinicalTrials.gov (Nov 2014).
Immuno Disease Comments: Phase 2 clinical trial for Psoriasis vulgaris has been completed. More recently, a Phase 1/2 study in FLT3 mutation positive AML has been initiated (NCT02418000).
sotrastaurin
Clinical Use: Sotrastaurin (AEB071) has been assessed in a number of clinical trials, for a wide variety of oncology indications, in autoimmune conditions such as plaque psoriasis, and also as an anti-rejection therapy following kidney/liver transplantation. Link here to ClinicalTrials.gov's listing of currently registered sotrastaurin trials. The only open trial (May 2017) is Phase 1 NCT02273219 in uveal melanoma.
Immuno Disease Comments: Completed Phase 2 clinical trial NCT00885196 for plaque psoriasis.
secukinumab  [  (Drugs.com) ]
Clinical Use: Secukinumab is approved by the US FDA for the treatment of plaque psoriasis.
Secukinumab also met its clinical endpoints in Phase III clinical trial for ankylosing spondylitis (NCT01649375) [1], and was FDA approved for this indication and psoriatic arthritis [21,23] in January 2016.
The antibody is also in Phase II clinical trial for multiple sclerosis (NCT01874340) based on results from experiments in an animal model of the disease (experimental autoimmune encephalomyelitis, EAE) and in vitro human cell assays [6].
Immuno Disease Comments: Approved therapeutic for plaque psoriasis.
tildrakizumab  [  (Drugs.com) ] 25
Clinical Use: Tildrakizumab completed Phase 3 clinical trial for plaque psoriasis (NCT01729754 and NCT01722331), and having shown significant clinical benefit over placebo and and a favourable safety profile [25], was FDA approved in March 2018, for the treatment of phototherapy candidate, adult patients with moderate to severe plaque psoriasis.
Immuno Disease Comments: Approved drug for moderate to severe plaque psoriasis.
itacitinib
Clinical Use: INCB039110 is being assessed in Phase II clinical trial as a potential treatment for indications such as rheumatoid arthritis (RA), post essential thrombocythemia myelofibrosis, chronic plaque psoriasis and non-small cell lung cancer (NSCLC).
Immuno Disease Comments: Phase 2 study NCT01634087 in psoriasis has been completed.
navarixin
Clinical Use: Navarixin (SCH-527123) has been evaluated in Phase II clinical trials for immune conditions such as allergen-induced asthma, chronic obstructive pulmonary disease (COPD) and psoriasis.
Immuno Disease Comments: Completed Phase 2 clinical trial NCT00684593 for psoriasis.
risankizumab
Clinical Use: Risankizumab has reached Phase II clinical trial for Crohn's disease (CD), psoriasis, and ankylosing spondylitis (AS). Results from the first-in-human proof-of-concept trial in patients with psoriasis are reported in [19].
Immuno Disease Comments: Phase 3 clinical candidate for psoriasis.
ZPL-3893787
Clinical Use: ZPL-3893787 has reached Phase 2 clinical trial for evaluation as an antiinflammatory agent in patients with plaque psoriasis (see NCT02618616), and a Phase 1 in atopic dermatitis has been completed.
Immuno Disease Comments: Completed Phase 2 trial in psoriasis (see NCT02618616).
bimosiamose
Clinical Use: Bimosiamose has completed Phase II clinical trials in patients with chronic obstructive pulmonary disease (COPD; inhaled bimosiamose, NCT01108913 [30]) and psoriasis (topically applied bimosiamose, NCT00823693)
Immuno Disease Comments: No progress beyond Phase 2 trial.
timolumab
Clinical Use: Timolumab (with research code BTT1023) is being evaluated in Phase II clinical trial NCT02239211, for its potential to treat patients with primary sclerosing cholangitis, an uncommon and progressive disease of the bile ducts characterised by inflammation and obliterative fibrosis. Phase I studies for RA and psoriasis have been completed (2010/11).
Immuno Disease Comments: Completed Phase 1 clinical trial NCT00871598.
crisaborole  [  (Drugs.com) ]
Clinical Use: Crisaborole (with research code AN2728) has completed Phase 3 clinical trials as a monotherapy for atopic dermatitis (NCT02118792 and NCT02118766) and has received FDA approval for treatment of mild-to-moderate atopic dermatitis in December 2016.
Immuno Disease Comments: Phase 2 clinical candidate for plaque psoriasis.
toreforant
Clinical Use: Toreforant failed to show clinical efficacy in a Phase 2 clinical trial in patients with active rheumatoid arthritis [28]. Phase 2 studies NCT01823016 and NCT02295865 in patients with uncontrolled, persistent asthma and moderate to severe plaque-type psoriasis respectively have been completed.
Immuno Disease Comments: No progress beyond Phase 2 trial.
fezakinumab
Clinical Use: Fezakinumab (ILV-094) has reached Phase 2 for atopic dermatitis (NCT01941537 ongoing), rheumatoid arthritis (NCT00883896 completed) and Phase 1 for psoriasis (NCT00563524 completed).
Immuno Disease Comments: Completed Phase 1 trial for psoriasis (see NCT00563524).
brazikumab
Clinical Use: Phase 1 clinical trials evaluating brazikumab as a monotherapy in mild to severe Crohn's disease (NCT01258205) and moderate to severe psoriasis (NCT01094093) have been completed. Phase 2 trials in subjects with active, moderate to severe Crohn's disease are ongoing (see NCT02574637 and NCT01714726).
Immuno Disease Comments: No progress beyond Phase 1 trial.
vunakizumab
Clinical Use: Vunakizumab (SHR-1314) does not appear to be registered in any clinical trials with ClinicalTrials.gov. Online searches suggest it is being trialled in China, in patients with psoriasis.
Immuno Disease Comments: In clinical trial in China.
amiselimod
Clinical Use: Amiselimod (MT-1303) has completed Phase 2 dose-finding clinical trials in patients with relapsing-remitting multiple sclerosis (NCT01742052) and moderate to severe chronic plaque psoriasis (NCT01987843). Phase 2 trials in Crohn's disease patients are underway.
Immuno Disease Comments: Phase 2 clinical candidate for plaque psoriasis.
itolizumab  [  (Drugs.com) ]
Clinical Use: Itolizumab has been licensed India since 2013 as a treatmant for chronic plaque psoriasis [5,14,20]. Itolizumab has also been evaluated in patients with rheumatoid arthritis [26].
Immuno Disease Comments: Approved drug for chronic plaque psoriasis.
PF-06263276
Immuno Disease Comments: Compelted Phase 1 trial in plaque psoriasis patients (see NCT02193815)
GSK2982772
Clinical Use: GSK2982772 is in Phase 2 clinical trials in psoriasis (NCT02776033), rheumatoid arthritis (NCT02858492), and ulcerative colitis (NCT02903966).
Immuno Disease Comments: Clinical candidate in psoriasis.
KD025
Clinical Use: KD025 is in Phase 2 clinical trials evaluating its anti-inflammatory and anti-fibrotic activity.
Immuno Disease Comments: Phase 2 clinical candidate for moderate to severe plaque psoriasis (NCT02852967).
metformin  [  (Drugs.com) ]
Clinical Use: Used in the management of non-insulin dependent type 2 diabetes as an adjunct to diet and exercise. Also used in the management of polycystic ovary syndrome (PCOS).
Metformin is combined with in Invokamet®, (also marketed as Vokanamet®) the first fixed-dose combination of an SGLT2 inhibitor with metformin to be approved (by the US FDA, 2014). Later in 2014, the US FDA approved a second SGLT2/metformin drug, Xigduo XR®, which contains (as dapagliflozin propanediol monohydrate PubChem CID 56841155) and metformin hydrochloride. The first approval of a metformin-containing drug mixture by the EMA was for Avandamet (rosiglitazone plus metformin), although this drug was later withdrawn from the market. Avandamet has been superceeded by newer and more effective anti-diabetes combination drugs.
Immuno Disease Comments: Clinical trial NCT02644954 was designed to test for efficacy of adjunct metformin in patients with moderate chronic plaque psoriasis, however it is unclear if this trial was ever initiated.
galectin-3
Immuno Disease Comments: Experiments in mouse models shows that galectin 3 deficiency contributes to the development of psoriasis-like inflammatory skin lesions. Notably galectin 3 expression is down-regulated in lesional skin from psoriasis patients, but not in their non-lesional skin.

References

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