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Psoriatic arthritis

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:1192
Name:Psoriatic arthritis
Associated with:0 target
17 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

GtoPdb Disease Summaries - Targets

Click on the target name to link to its detailed view page

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 Psoriatic arthritis

Ligands

GtoPdb Disease Summaries - Ligands

Click ligand name to view ligand summary page

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

Click the arrow in the final column to expand comments

  • 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
filgotinib
Immuno Disease Comments: A Phase 2 clinical candidate for PsA (see NCT03101670).
Clinical Use: Filgotinib was advanced to evaluation in patients with rheumatoid arthritis, Crohn's disease and ulcerative colitis. Click here to link to ClinicalTrials.gov's complete listing of filgotinib studies. In October 2019 Gliead Sciences and Galapagos issued a press release which announced sustained efficacy, safety and tolerability of filgotinib from 12-52 weeks in RA patients in the Phase 3 FINCH1 (NCT02889796) & FINCH3 (NCT02886728) trials [12].

In August 2020, Gilead announed that the FDA had rejected their filing for approval of filgotinib in RA in a complete response letter, that expressed concerns about toxicity (on sperm concentrations) of the 200mg dose. The FDA want to review results from the ongoing MANTA and MANTA-RAy trials that are expected in the first half of 2021. However, late September 2020 saw EMA and Japanese PMDA approvals granted to filgotinib for the treatment of moderate to severe RA.
Publication of results from ulcerative colitis trials is pending, although positive indications (particulary in relation to response rates and safety) were presented at the United European Gastroenterology Week virtual meeting (October 11-13, 2020). | View clinical data
ixekizumab 23
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 [11], and Phase 3 results are reviewed in [9]. 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 [14], 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 2 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 [15] 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 [17] and has broad spectrum activity across isoforms from all four PDE4 sub-families (IC50s 10-100nM) [25]. | 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 [32]. | 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 moderate to severe plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis. | View clinical data
Bioactivity Comments: The patent covering the production and use of ustekinumab (US6902734 [13]) 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
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 2I), moderate to severe plaque psoriasis (Phase 2I) and asthma (Phase 2) are ongoing. Encouraging results from a Phase 2 study have been reported [19]. | View clinical data
Bioactivity Comments: BLAST searches using the peptide sequences of the heavy and light chains of brodalumab link to patent US7767206 [28], and monoclonal antibody clone AMH14/AML14. | 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 2I clinical trial for ankylosing spondylitis (NCT01649375) [1], and was FDA approved for this indication and psoriatic arthritis [18,21] in January 2016.
The antibody is also in Phase 2 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 [8]. | 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 [31]), psoriatic arthritis (NCT01490450, results in [20]), cachexia resulting from non-small cell lung cancer [2,16], 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.

SARS-CoV-2 and COVID-19: Clazakizumab has been entered into clinical trials in patients with COVID-19, with a particular focus on assessing its efficacy in those with life-threatening hyperinflammation. | 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
upadacitinib
Immuno Disease Comments: Phase 3 clinical candidate for PsA- see NCT03104374
Clinical Use: Upadacitinib (ABT-494) completed successful Phase 3 clinical evaluation for rheumatoid arthritis (RA) [10,22,27], and was granted FDA approval in August 2019 and EMA approval in December 2019, as a treatment for patients with moderate-severe active RA that is inadequately controlled by [7]. Evaluation of upadacitinib's potential in additional immune-mediated conditions (psoriatic arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, atopic dermatitis, SLE and temporal arteritis) are ongoing [24,26,29]. Click here to link to ClinicalTrials.gov's list of ABT-494 studies.
Abbvie reported (in a press release) that upadacitinib met its primary and secondary endpoints in Phase 3 evaluation in psoriatic arthritis (October 2019). No new safety risks were detected. Depending on the dose administered, 25-29% of patients achieved minimal disease activity at week 24 of the study. Formal publication of these results will follow.
FDA approval was expanded in May 2023, to include treatment of moderate-severe active Crohn's disease that has not responded to anti-TNFα drugs. | View clinical data
Bioactivity Comments: In a kinase screening panel, only two other kinases, Rock1 and Rock2 have IC50s below 1000nM [30]. | View biological activity

References

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1. Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, Deodhar A, Porter B, Martin R, Andersson M et al.. (2015) Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med, 373 (26): 2534-48. [PMID:26699169]

2. Bayliss TJ, Smith JT, Schuster M, Dragnev KH, Rigas JR. (2011) A humanized anti-IL-6 antibody (ALD518) in non-small cell lung cancer. Expert Opin Biol Ther, 11 (12): 1663-8. [PMID:21995322]

3. Bouma G, Zamuner S, Hicks K, Want A, Oliveira J, Choudhury A, Brett S, Robertson D, Felton L, Norris V et al.. (2017) CCL20 neutralization by a monoclonal antibody in healthy subjects selectively inhibits recruitment of CCR6+ cells in an experimental suction blister. Br J Clin Pharmacol, 83 (9): 1976-1990. [PMID:28295451]

4. Davis IC, Randell J, Davis SN. (2015) Immunotherapies currently in development for the treatment of type 1 diabetes. Expert Opin Investig Drugs, 24 (10): 1331-41. [PMID:26364507]

5. de Wit J, Al-Mossawi MH, Hühn MH, Arancibia-Cárcamo CV, Doig K, Kendrick B, Gundle R, Taylor P, Mcclanahan T, Murphy E et al.. (2016) RORγt inhibitors suppress TH17 responses in inflammatory arthritis and inflammatory bowel disease. J Allergy Clin Immunol, 137 (3): 960-3. [PMID:26611672]

6. Douthwaite J, Moisan J, Privezentzev C, Soskic B, Sabbah S, Cohen S, Collinson A, England E, Huntington C, Kemp B et al.. (2017) A CD80-Biased CTLA4-Ig Fusion Protein with Superior In Vivo Efficacy by Simultaneous Engineering of Affinity, Selectivity, Stability, and FcRn Binding. J Immunol, 198 (1): 528-537. [PMID:27881707]

7. Duggan S, Keam SJ. (2019) Upadacitinib: First Approval. Drugs, 79 (16): 1819-1828. [PMID:31642025]

8. Elain G, Jeanneau K, Rutkowska A, Mir AK, Dev KK. (2014) The selective anti-IL17A monoclonal antibody secukinumab (AIN457) attenuates IL17A-induced levels of IL6 in human astrocytes. Glia, 62 (5): 725-35. [PMID:24677511]

9. Farahnik B, Beroukhim K, Zhu TH, Abrouk M, Nakamura M, Singh R, Lee K, Bhutani T, Koo J. (2016) Ixekizumab for the Treatment of Psoriasis: A Review of Phase III Trials. Dermatol Ther (Heidelb), 6 (1): 25-37. [PMID:26910853]

10. Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, Durez P, Ostor AJ, Li Y, Zhou Y et al.. (2019) Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis Rheumatol, 71 (11): 1788-1800. [PMID:31287230]

11. Genovese MC, Greenwald M, Cho CS, Berman A, Jin L, Cameron GS, Benichou O, Xie L, Braun D, Berclaz PY et al.. (2014) A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors. Arthritis Rheumatol, 66 (7): 1693-704. [PMID:24623718]

12. Gilead Sciences. Press release- Gilead and Galapagos Announce Efficacy and Safety Results of Filgotinib Through 52 Weeks in FINCH 1 and FINCH 3 Studies in Rheumatoid Arthritis. Accessed on 16/10/2019. Modified on 16/10/2019. gilead.com, https://www.gilead.com/news-and-press/press-room/press-releases/2019/10/gilead-and-galapagos-announce-efficacy-and-safety-results-of-filgotinib-through-52-weeks-in-finch-1-and-finch-3-studies-in-rheumatoid-arthritis

13. Giles-Komar J, Knight DM, Peritt D, Scallon B, Shealy D. (2005) Also an IL-12 anti-idiotype antibody to the antibody. Patent number: US6902734. Assignee: Centocor, Inc.. Priority date: 07/08/2000. Publication date: 07/06/2005.

14. Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, Reich K, Amato D, Ball SG, Braun DK et al.. (2016) Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med, 375 (4): 345-56. [PMID:27299809]

15. Ludvigsson J. (2016) Therapies to Preserve β-Cell Function in Type 1 Diabetes. Drugs, 76 (2): 169-85. [PMID:26645223]

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17. Man HW, Schafer P, Wong LM, Patterson RT, Corral LG, Raymon H, Blease K, Leisten J, Shirley MA, Tang Y et al.. (2009) Discovery of (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl] acetamide (apremilast), a potent and orally active phosphodiesterase 4 and tumor necrosis factor-alpha inhibitor. J Med Chem, 52 (6): 1522-4. [PMID:19256507]

18. McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, van der Heijde D, Landewé R, Conaghan PG, Gottlieb AB et al.. (2015) Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 386 (9999): 1137-46. [PMID:26135703]

19. Mease PJ, Genovese MC, Greenwald MW, Ritchlin CT, Beaulieu AD, Deodhar A, Newmark R, Feng J, Erondu N, Nirula A. (2014) Brodalumab, an Anti-IL17RA Monoclonal Antibody, in Psoriatic Arthritis. N Engl J Med, 370 (24): 2295-2306. [PMID:24918373]

20. Mease PJ, Gottlieb AB, Berman A, Drescher E, Xing J, Wong R, Banerjee S. (2016) The Efficacy and Safety of Clazakizumab, an Anti-Interleukin-6 Monoclonal Antibody, in a Phase IIb Study of Adults With Active Psoriatic Arthritis. Arthritis Rheumatol, 68 (9): 2163-73. [PMID:27059799]

21. Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, Landewé R, Nash P, Pricop L, Yuan J et al.. (2015) Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med, 373 (14): 1329-39. [PMID:26422723]

22. Mohamed MF, Klünder B, Camp HS, Othman AA. (2019) Exposure-Response Analyses of Upadacitinib Efficacy in Phase II Trials in Rheumatoid Arthritis and Basis for Phase III Dose Selection. Clin Pharmacol Ther, 106 (6): 1319-1327. [PMID:31194885]

23. Nash P, Kirkham B, Okada M, Rahman P, Combe B, Burmester GR, Adams DH, Kerr L, Lee C, Shuler CL et al.. (2017) Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet, 389 (10086): 2317-2327. [PMID:28551073]

24. Pérez-Jeldres T, Tyler CJ, Boyer JD, Karuppuchamy T, Yarur A, Giles DA, Yeasmin S, Lundborg L, Sandborn WJ, Patel DR et al.. (2019) Targeting Cytokine Signaling and Lymphocyte Traffic via Small Molecules in Inflammatory Bowel Disease: JAK Inhibitors and S1PR Agonists. Front Pharmacol, 10: 212. [PMID:30930775]

25. Schafer PH, Parton A, Capone L, Cedzik D, Brady H, Evans JF, Man HW, Muller GW, Stirling DI, Chopra R. (2014) Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. Cell Signal, 26 (9): 2016-29. [PMID:24882690]

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27. Smolen JS, Pangan AL, Emery P, Rigby W, Tanaka Y, Vargas JI, Zhang Y, Damjanov N, Friedman A, Othman AA et al.. (2019) Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet, 393 (10188): 2303-2311. [PMID:31130260]

28. Tocker J, Mehlin C, Lim AC. (2010) Neutralizing determinants of IL-17 Receptor A and antibodies that bind thereto. Patent number: US7767206. Assignee: Amgen Inc.. Priority date: 02/10/2006. Publication date: 03/08/2010.

29. Torgutalp M, Poddubnyy D. (2018) Emerging treatment options for spondyloarthritis. Best Pract Res Clin Rheumatol, 32 (3): 472-484. [PMID:31171316]

30. Voss JW, Camp HS, Padley RJ. (2015) Jak1 selective inhibitor and uses thereof. Patent number: WO2015061665. Assignee: Abbvie Inc.. Priority date: 24/10/2013. Publication date: 30/04/2015.

31. Weinblatt ME, Mease P, Mysler E, Takeuchi T, Drescher E, Berman A, Xing J, Zilberstein M, Banerjee S, Emery P. (2015) The efficacy and safety of subcutaneous clazakizumab in patients with moderate-to-severe rheumatoid arthritis and an inadequate response to methotrexate: results from a multinational, phase IIb, randomized, double-blind, placebo/active-controlled, dose-ranging study. Arthritis Rheumatol, 67 (10): 2591-600. [PMID:26138593]

32. Zhong W, Zhao L, Liu T, Jiang Z. (2017) IL-22-producing CD4+T cells in the treatment response of rheumatoid arthritis to combination therapy with methotrexate and leflunomide. Sci Rep, 7: 41143. [PMID:28117352]