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Uveitis

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:1198
Name:Uveitis
Associated with:0 target
6 immuno-relevant ligands
Description
Inflammation of the uvea or uveal tract; includes anterior uveitis, intermediate uveitis and posterior uveitis.
Database Links
Disease Ontology: DOID:13141

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 Uveitis

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
piclidenoson
Immuno Disease Comments: Clinical candidate for uveitis (Phase 2 NCT01905124)
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 2I, NCT02647762 [10]; plaque psoriasis, Phase 2 [1]; uveitis Phase 2) and glaucoma (Phase 2, NCT01033422 [4]). | View clinical data
rimexolone
Immuno Disease Comments: Approved drug for uveitis.
Clinical Use: Used to treat inflammation of the eye. | View clinical data
difluprednate
Immuno Disease Comments: Specifically approved for anterior uveitis.
Clinical Use: Approved to treat eye pain and inflammation following opthalmic surgery and to treat anterior uveitis. | View clinical data
Bioactivity Comments: Difluprednate has a reported Ki of 0.78nM [8] in a glucocorticoid receptor binding assay. As it is clear from the structure of this drug that it is a glucocorticoid receptor agonist we have tagged this receptor as the primary drug target, despite being unable to identify publicly available bioactivity data at the human glucocorticoid receptor. | View biological activity
gevokizumab
Immuno Disease Comments: Approved therapeutic for uveitis.
Clinical Use: This monoclonal antibody drug has been granted orphan status in the US (FDA 2012) and EU (EMA 2013) for the treatment of the rare disease, chronic non-infectious uveitis (including that associated with Behçet’s disease). | View clinical data
Bioactivity Comments: The inhibitory effects gevokizumab of arise from a classic allosteric ternary complex mechanism whereby the antibody binds to the orthosteric agonist IL-1β, modulating the interaction with the orthosteric site on the receptor [5,7].
Sequence analysis of the peptide sequence of gevokizumab indicate a match for sequence ID 15 from patent US7531166 [6], suggesting that gevokizumab derives from clone AB7. Data for clone AB7 is included in the interaction table below. | View biological activity
sarilumab
Immuno Disease Comments: Completed Phase 2 clinical trial for non-infectious uveitis (see NCT01900431).
Clinical Use: Sarilumab was granted FDA approval as a treatment for moderate to severe active RA in May 2017 (with EMA approval granted in June 2017), following evaluation in several clinical trials, either as a monotherapy (eg NCT02121210) or in combination with other drugs such as , , and .
Click here to link to ClinicalTrials.gov's listing of Phase 3 sarilumab trials. A Phase 2 study for non-infectious uveitis (NCT01900431) has been completed, whereas a Phase 2 extension study (NCT01118728) for ankylosing spondylitis was terminated.

SARS-CoV-2 and COVID-19: Sarilumab has been evaluated for potential to reduce exaggerated inflammation in hospitalised patients with COVID-19. The Phase 2/3 clinical trial (NCT04315298) did not meet its primary or secondary endpoints in these patients and the trial was terminated. An Italian trial also failed to find mortality benefit [2]. However, early in 2021, data was reported from a small cohort of severely ill, mechanically ventilated COVID-19 patients in the REMAP-CAP trial ( NCT02735707) who received sarilumab. The information released (data not yet published) suggested that sarilumab (compared to standard care) significantly reduced mortality and that patients treated with this mAb were able to leave intensive care 7-10 days earlier than those who didn't receive the drug. Similar efficacy was observed in patients who received the alternative anti-IL-6R mAb . The effects of mAb therapy appeared to be in addition to the benefit provided by . | View clinical data
gevokizumab 3,9
Immuno Disease Comments: Gevokizumab is a FDA and EMA orphan drug for the management of chronic non-infectious uveitis.
Clinical Use: This monoclonal antibody drug has been granted orphan status in the US (FDA 2012) and EU (EMA 2013) for the treatment of the rare disease, chronic non-infectious uveitis (including that associated with Behçet’s disease). | View clinical data
Bioactivity Comments: The inhibitory effects gevokizumab of arise from a classic allosteric ternary complex mechanism whereby the antibody binds to the orthosteric agonist IL-1β, modulating the interaction with the orthosteric site on the receptor [5,7].
Sequence analysis of the peptide sequence of gevokizumab indicate a match for sequence ID 15 from patent US7531166 [6], suggesting that gevokizumab derives from clone AB7. Data for clone AB7 is included in the interaction table below. | View biological activity

References

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1. David M, Akerman L, Ziv M, Kadurina M, Gospodinov D, Pavlotsky F, Yankova R, Kouzeva V, Ramon M, Silverman MH et al.. (2012) Treatment of plaque-type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial. J Eur Acad Dermatol Venereol, 26 (3): 361-7. [PMID:21504485]

2. Della-Torre E, Campochiaro C, Cavalli G, De Luca G, Napolitano A, La Marca S, Boffini N, Da Prat V, Di Terlizzi G, Lanzillotta M et al.. (2020) Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: an open-label cohort study. Ann Rheum Dis, 79 (10): 1277-1285. [PMID:32620597]

3. EMA. Rare disease (orphan) designations- gevokizumab. Accessed on 02/04/2018. Modified on 02/04/2018. European Medicines Agency, http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/landing/orphan_search.jsp&mid=WC0b01ac058001d12b&source=homeMedSearch&keyword=gevokizumab&isNewQuery=true

4. Fishman P, Cohen S, Bar-Yehuda S. (2013) Targeting the A3 adenosine receptor for glaucoma treatment (review). Mol Med Rep, 7 (6): 1723-5. [PMID:23563604]

5. Issafras H, Corbin JA, Goldfine ID, Roell MK. (2014) Detailed mechanistic analysis of gevokizumab, an allosteric anti-IL-1β antibody with differential receptor-modulating properties. J Pharmacol Exp Ther, 348 (1): 202-15. [PMID:24194526]

6. Masat L, Haak-Frendscho M, Chen G, Horwitz A, Roell M. (2009) IL-1β binding antibodies and fragments thereof. Patent number: US7531166. Assignee: Xoma Technology, Ltd. Priority date: 27/02/2015. Publication date: 12/03/2010.

7. Roell MK, Issafras H, Bauer RJ, Michelson KS, Mendoza N, Vanegas SI, Gross LM, Larsen PD, Bedinger DH, Bohmann DJ et al.. (2010) Kinetic approach to pathway attenuation using XOMA 052, a regulatory therapeutic antibody that modulates interleukin-1beta activity. J Biol Chem, 285 (27): 20607-14. [PMID:20410301]

8. Tajika T, Waki M, Tsuzuki M, Kida T, Sakaki H. (2011) Pharmacokinetic features of difluprednate ophthalmic emulsion in rabbits as determined by glucocorticoid receptor-binding bioassay. J Ocul Pharmacol Ther, 27 (1): 29-34. [PMID:21182429]

9. US FDA. Gevokizumab orphan drug designations. Accessed on 02/04/2018. Modified on 02/04/2018. FDA Orphan Drug Designations and Approvals, https://www.accessdata.fda.gov/scripts/opdlisting/oopd/listResult.cfm

10. Varani K, Padovan M, Govoni M, Vincenzi F, Trotta F, Borea PA. (2010) The role of adenosine receptors in rheumatoid arthritis. Autoimmun Rev, 10 (2): 61-4. [PMID:20691813]