Psoriatic arthritis

Disease ID:1192
Name:Psoriatic arthritis
Associated with:0 target
16 immuno-relevant ligands
Synonyms
arthritis psoriatica | arthropathic psoriasis
Description
Co-morbid symptoms similar to arthritis experienced by patients with psoriasis.
Database Links
Disease Ontology: DOID:9008

Targets

No target related data available for Psoriatic arthritis

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
filgotinib
Immuno Disease Comments: A Phase 2 clinical candidate for PsA (see NCT03101670).
Clinical Use: Filgotinib is in Phase II clinical trial for rheumatoid arthritis and Crohn's disease. Click here to link to ClinicalTrials.gov's complete listing of filgotinib Phase II trials. | View clinical data
brodalumab
Immuno Disease Comments: Clinical candidate for PsA.
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 [16]. | View clinical data
Bioactivity Comments: BLAST searches using the peptide sequences of the heavy and light chains of brodalumab link to patent US7767206 [21], and monoclonal antibody clone AMH14/AML14. | View biological activity
ixekizumab 19
Immuno Disease Comments: Phase 3 clinical candidate for PsA (see NCT02349295).
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 [8]. 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 [11], showing longer term efficacy (with ~80% of patients seeing at least a 75% improvement in their skin symptoms at 60 weeks). | View clinical data
remtolumab
Immuno Disease Comments: Phase 2 clinical candidate for PsA- see NCT02429895, which indicates that investigation in PsA has been terminated on business grounds.
Clinical Use: Remtolumab has reached Phase 2 clinical trial for rheumatoid arthritis and psoriatic arthritis. | View clinical data
abatacept
Immuno Disease Comments: Approved drug for PsA.
Clinical Use: Used to treat moderate to severe rheumatoid arthritis and juvenile rheumatoid arthritis. In July 2017, FDA approval was extended to include treatment of active psoriatic arthritis.
A Phase II clinical trial (NCT00505375) has been completed, evaluating the ability of abatacept to stop autoimmune destruction of any remaining active β cells in patients recently diagnosed with type 1 diabetes mellitus- see [12] for an explanation of the rationale behind this therapeutic approach, and [4] which points to some of its drawbacks. | View clinical data
Bioactivity Comments: In a cell based CD80/86 inhibition assay abatacept inhibits IL-2 release with an IC50 of 22.6 nM [6]. | View biological activity
GSK3050002
Immuno Disease Comments: Phase 1 clinical candidate for PsA.
Clinical Use: Phase 1 clinical study in healthy subjects (NCT01984047) revealed no major safety concerns, and provided proof-of-concept for this mechanism of preventing recruitment of CCR6+ cells to inflammatory sites [3]. A Phase 1 study in psoriatic arthritis (NCT02671188) is registered with ClinicalTrials.gov, but is not yet recruiting patients. | View clinical data
apremilast
Immuno Disease Comments: Approved drug for PsA.
Clinical Use: Apremilast is approved to treat psoriatic arthritis (PsA). This drug is also in clinical trial as a potential treatment for several other inflammatory conditions. View a list of these trials at ClinicalTrials.gov. In the US and EU, apremilast has been granted orphan desigantion for the treatment of Behçet disease, an auto-immune disease which damages blood vessels and causes sores on mucosal membranes and occular and vascular inflammation.
In September 2014, the US FDA granted approval for the treatment of patients with moderate to severe plaque psoriasis, making Otezla® the first and only PDE4 inhibitor available for this indication. | View clinical data
Bioactivity Comments: Apremilast inhibits a crude extract of human PDE4 with an IC50 of 74nM [14] and has broad spectrum activity across isoforms from all four PDE4 sub-families (IC50s 10-100nM) [20]. | View biological activity
methotrexate
Immuno Disease Comments: Approved drug for PsA.
Clinical Use: Anti-tumour agent used in the treatment of acute lymphocytic leukemia (ALL), meningeal leukemia, non-Hogkin's lymphoma, breast, lung and head and neck cancers. Also indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole, and in the treatment of autoimmune conditions including severe psoriasis and rheumatoid arthritis. The first oral methotraxate solution (Xatmep®) was FDA approved in April 2017 for the treatment of ALL and polyarticular juvenile idiopathic arthritis (pJIA) in pediatric patients. A 2017 a paper reported that a combination of methotrexate with leflunomide relieves the immune defects and ameliorates symptoms of rheumatoid arthritis [23]. | View clinical data
IL-17A
Immuno Disease Comments: Approved therapy for PsA.
lymphotoxin-α
Immuno Disease Comments: Approved therapy for PsA.
ustekinumab
Immuno Disease Comments: An anti-IL-12B therapy approved to treat PsA.
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. | View clinical data
Bioactivity Comments: The patent covering the production and use of ustekinumab (US6902734 [10]) does not provide affinity values for specific antibody clones, therefore we have included the stated range of affinities determined in the production and testing process in the interaction table below.. | View biological activity
secukinumab
Immuno Disease Comments: Approved therapeutic for PsA.
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 [15,18] 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 [7]. | View clinical data
MRL-367
Immuno Disease Comments: Experimental compound with predicted application in PsA.
Bioactivity Comments: In a RORγ/Gal4 cell-based reporter assay MRL-367 inhibits RORγt with an IC50 of 41nM, and shows no significant activity against a panel of related nuclear hormone receptors [5]. | View biological activity
MRL-248
Immuno Disease Comments: Experimental compound with predicted application in PsA.
Bioactivity Comments: In a RORγ/Gal4 cell-based reporter assay MRL-248 inhibits RORγt with an IC50 of 118nM, and shows no significant activity against a panel of related nuclear hormone receptors [5]. | View biological activity
clazakizumab
Immuno Disease Comments: No progress beyond Phase 2 trial.
Clinical Use: Phase 2 clinical trials in patients with active rheumatoid arthritis (NCT01373151, results reported in [22]), psoriatic arthritis (NCT01490450, results in [17]), cachexia resulting from non-small cell lung cancer [2,13], acute graft versus host disease (GvHD) and oral mucositis caused by head and neck cancer have been completed. Click here to link to ClinicalTrials.gov's list of clazakizumab (ALD518 and BMS-945429) trials. | View clinical data
metformin
Immuno Disease Comments: Clinical trial NCT02188654 that was designed to evaluate the anti-inflammatory and immunosuppressant efficacy of metformin in patients with PsA has been completed. No results have been published.
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. | View clinical data
Bioactivity Comments: As the molecular mechanism of metformin is incompletely understood we have not tagged a primary drug target. | View biological activity

References

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