Crohn's disease

Disease ID:1016
Name:Crohn's disease
Associated with:4 targets
1 immuno-relevant targets
26 immuno-relevant ligands
Synonyms
Crohn disease | Inflammatory bowel disease 1; IBD1
Database Links
Disease Ontology: DOID:8778
OMIM: 266600
Orphanet: ORPHA206

Targets

regulator of G-protein signaling 1
Comments:  Crohn's disease AND ulcerative colitis
References:  2
heat shock protein family A (Hsp70) member 1 like
Comments:  Genetic mutations that cause amino acid changes in the HSPA1L protein have been identified in patients with CD.

Ligands

Ligand Approved Immuno References Clinical comments
ozanimod
Clinical Use: Ozanimod has reached Phase III clinical trial for its potential antiinflammatory effects in relapsing multiple sclerosis and ulcerative colitis.
Immuno Disease Comments: Phase 2 clinical candidate for CD (see NCT02531113).
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 active CD- see NCT02891226.
natalizumab  [  (Drugs.com) ]
Clinical Use: Used in the treatment of relapsing forms of multiple sclerosis, and in the management of Crohn's disease. However, natalizumab is not widely prescribed due to safety concerns around progressive multifocal leukoencephalopathy (PML).
Immuno Disease Comments: Approved drug for CD.
fontolizumab 4,10
Clinical Use: Fontolizumab (HuZAF) has completed Phase 2 clinical trial in patients with moderate to severe Crohn's disease (NCT00072943). Results showed that fontolizumab was well tolerated by these patients, and effected increased rates of clinical response and remission compared with placebo [4,10]. A Phase 2 trial in rheumatoid arthritis (NCT00281294) was terminated early because the first phase failed to meet the endpoint.
Immuno Disease Comments: Fontolizumab has completed Phase 2 clinical trial in patients with moderate to severe Crohn's disease- see NCT00072943
prednisolone  [  (Drugs.com) ]
Clinical Use: This drug used as an antiinflammatory or immunosuppressive agent and is indicated for the treatment of various inflammatory pathologies, including acute asthma, suppression of inflammatory and allergic disorders, ulcerative colitis, Crohn's disease, idiopathic thrombocytopenic purpura, rheumatoid arthritis, polymyalgia rheumatica, systemic lupus erythematosus and chronic obstructive pulmonary disease (COPD).
Immuno Disease Comments: Glucocorticoid drug used to treat many inflammatory condtions including CD.
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 [5].
Immuno Disease Comments: Anti-TNFα monoclonal antibody therapy approved for Crohn's disease.
infliximab  [  (Drugs.com) ]
Clinical Use: Used in the management of rheumatoid arthritis (in combination with ), ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease [14] and ulcerative colitis.
Immuno Disease Comments: Approved monoclonal antibody therapy for Crohn's disease.
certolizumab pegol  [  (Drugs.com) ]
Clinical Use: Used to treat rheumatoid arthritis and Crohn's disease [1]. May also have some effect in related conditions such as axial spondyloarthritis [12]. The EMA refused Europe-wide approval for the use of this drug, but individual nations have granted approval for its use (e.g. the UK in 2009).
Immuno Disease Comments: An anti-TNFα therapy approved for CD.
azathioprine  [  (Drugs.com) ]
Clinical Use: Used to reduce organ rejection in transplant patients and to treat autoimmune diseases such as rheumatoid arthritis, Crohn's disease, lupus erythematosus and ulcerative colitis.
Immuno Disease Comments: Approved drug for CD.
vedolizumab  [  (Drugs.com) ]
Clinical Use: Approved to treat adult patients with moderate to severe ulcerative colitis or moderate to severe Crohn‘s disease.
Immuno Disease Comments: Approved therapeutic for CD.
AZ11657312 (salt free)
Immuno Disease Comments: Experimental compound.
AZD9056
Clinical Use: AZD9056 was developed for the treatment of inflammatory conditions such as rheumatoid arthritis (RA), chronic obstructive pulmonary disease (COPD) and Crohn’s disease. Phase II trial NCT00520572 for RA has been completed. There are no active trials in progress (Nov 2014).
Immuno Disease Comments: Developed with potential for treating CD, but development was discontinued.
filgotinib
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.
Immuno Disease Comments: Phase 2 clinical candidate for both perianal fistulizing (NCT03077412) and small bowel (NCT03046056) CD.
mongersen
Clinical Use: A Phase II clinical trial has shown promising results in Crohn's disease, with higher rates of remission being reported in patients receiving mongersen compared to those in the placebo group [9].
Immuno Disease Comments: Phase 3 clinical candidate for CD (see NCT02641392).
etrolizumab
Clinical Use: Etrolizumab is being evaluated in Phase III clinical trial as a potential treatment for Crohn's disease and ulcerative colitis [15].
Immuno Disease Comments: Phase 3 clinical candidate for CD.
dectrekumab
Clinical Use: Dectrekumab (QBX258) reached Phase II clinical trial as a potential biologic therapy for several immune conditions, including idiopathic pulmonary fibrosis (IPF), asthma, eosinophilic esophagitis [11] (proof of principle study NCT01022970), Crohn's disease, keloids and allergic rhinitis. As of May 2017, there are no active dectrekumab studies.
Immuno Disease Comments: Phase 2 trial NCT01316601 in CD has been completed.
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 [8].
Immuno Disease Comments: Phase 3 clinical candidate for CD (see NCT03105102).
vercirnon
Clinical Use: Three out of four Phase III clinical trials evaluating vercirnon (using research code GSK1605786A) in Crohn's disease were terminated due to lack of efficacy.
Immuno Disease Comments: Failed to show clinical efficiency in Phase 3 trials.
briakinumab
Clinical Use: Results from a Phase 2 clinical trial (NCT00292396) evaluating briakinumab in patients with moderate to severe chronic plaque psoriasis are reported in [7]. Several Phase 3 trials comparing briakinumab against placebo, and (two approved anti-psoriatic drugs) for moderate to severe chronic plaque psoriasis (link here to a list of these trials on ClinicalTrials.gov) have been completed. Clinical development of briakinumab for rheumatoid arthritis, Crohn's disease and multiple sclerosis has been terminated. As of May 2017, there are no active clinical trials evaluating this antibody.
Immuno Disease Comments: Clinical development for CD has been terminated.
upadacitinib
Clinical Use: ABT-494 has reached Phase 3 clinical trial for rheumatoid arthritis (RA). Evaluation of upadacitinib's potential in additional immune-mediated conditions (psoriatic arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis and atopic dermatitis) are ongoing. Click here to link to ClinicalTrials.gov's list of Phase 3 ABT-494 trilas.
Immuno Disease Comments: Phase 3 clinical candidate for CD.
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: Phase 2 clinical candidate for CD (see NCT02574637).
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 CD.
mucosal addressin cell adhesion molecule 1
Immuno Disease Comments: A gut-specific ligand being investigated as a drug target for inflammatory bowel conditions.
PF-00547659
Clinical Use: PF-00547659 has completed Phase 2 clinical trials for ulcerative colitis and Crohn's disease. Results from Phase 2 ulcerative colitis trial NCT01620255 were published by Vermeire et al. (2017) [16]
Immuno Disease Comments: Phase 2 clinical candidate for CD (see completed study NCT01298492).
deflazacort  [  (Drugs.com) ]
Clinical Use: Deflazacort can be prescribed for many inflammatory conditions including asthma, rheumatoid arthritis, Crohn's disease, juvenile chronic arthritis, idiopathic thrombocytopenic purpura, polymyalgia rheumatica, systemic lupus erythematosus and ulcerative colitis. More recently approved to treat Duchenne muscular dystrophy [3].
Immuno Disease Comments: Approved corticosteroid that can be prescribed for CD.
teduglutide  [  (Drugs.com) ]
Clinical Use: Teduglutide is used in the treatment of short bowel syndrome [6,17].
Immuno Disease Comments: Teduglutide has completed Phase 2 clinical trials in Crohn's disease patients- see NCT00072839 and the follow on trial NCT00308438

References

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1. Choy EH, Hazleman B, Smith M, Moss K, Lisi L, Scott DG, Patel J, Sopwith M, Isenberg DA. (2002) Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial. Rheumatology (Oxford), 41 (10): 1133-7. [PMID:12364632]

2. Gibbons DL, Abeler-Dörner L, Raine T, Hwang IY, Jandke A, Wencker M, Deban L, Rudd CE, Irving PM, Kehrl JH et al.. (2011) Cutting Edge: Regulator of G protein signaling-1 selectively regulates gut T cell trafficking and colitic potential. J. Immunol., 187 (5): 2067-71. [PMID:21795595]

3. Griggs RC, Miller JP, Greenberg CR, Fehlings DL, Pestronk A, Mendell JR, Moxley 3rd RT, King W, Kissel JT, Cwik V et al.. (2016) Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy. Neurology, 87 (20): 2123-2131. [PMID:27566742]

4. Hommes DW, Mikhajlova TL, Stoinov S, Stimac D, Vucelic B, Lonovics J, Zákuciová M, D'Haens G, Van Assche G, Ba S et al.. (2006) Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease. Gut, 55 (8): 1131-7. [PMID:16507585]

5. Jaffe GJ, Dick AD, Brézin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D et al.. (2016) Adalimumab in Patients with Active Noninfectious Uveitis. N. Engl. J. Med., 375 (10): 932-43. [PMID:27602665]

6. Jeppesen PB. (2012) Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome. Therap Adv Gastroenterol, 5 (3): 159-71. [PMID:22570676]

7. Kimball AB, Gordon KB, Langley RG, Menter A, Chartash EK, Valdes J, ABT-874 Psoriasis Study Investigators. (2008) Safety and efficacy of ABT-874, a fully human interleukin 12/23 monoclonal antibody, in the treatment of moderate to severe chronic plaque psoriasis: results of a randomized, placebo-controlled, phase 2 trial. Arch Dermatol, 144 (2): 200-7. [PMID:18283176]

8. Krueger JG, Ferris LK, Menter A, Wagner F, White A, Visvanathan S, Lalovic B, Aslanyan S, Wang EE, Hall D et al.. (2015) Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J. Allergy Clin. Immunol., 136 (1): 116-124.e7. [PMID:25769911]

9. Monteleone G, Neurath MF, Ardizzone S, Di Sabatino A, Fantini MC, Castiglione F, Scribano ML, Armuzzi A, Caprioli F, Sturniolo GC et al.. (2015) Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease. N. Engl. J. Med., 372 (12): 1104-13. [PMID:25785968]

10. Reinisch W, de Villiers W, Bene L, Simon L, Rácz I, Katz S, Altorjay I, Feagan B, Riff D, Bernstein CN et al.. (2010) Fontolizumab in moderate to severe Crohn's disease: a phase 2, randomized, double-blind, placebo-controlled, multiple-dose study. Inflamm. Bowel Dis., 16 (2): 233-42. [PMID:19637334]

11. Rothenberg ME, Wen T, Greenberg A, Alpan O, Enav B, Hirano I, Nadeau K, Kaiser S, Peters T, Perez A et al.. (2015) Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis. J. Allergy Clin. Immunol., 135 (2): 500-7. [PMID:25226850]

12. Song IH, Rudwaleit M. (2013) Certolizumab pegol in axial spondyloarthritis. Expert Rev Clin Immunol, 9 (12): 1161-72. [PMID:24215406]

13. Takahashi S, Andreoletti G, Chen R, Munehira Y, Batra A, Afzal NA, Beattie RM, Bernstein JA, Ennis S, Snyder M. (2017) De novo and rare mutations in the HSPA1L heat shock gene associated with inflammatory bowel disease. Genome Med, 9 (1): 8. [PMID:28126021]

14. van Dullemen HM, van Deventer SJ, Hommes DW, Bijl HA, Jansen J, Tytgat GN, Woody J. (1995) Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology, 109 (1): 129-35. [PMID:7797011]

15. Vermeire S, O'Byrne S, Keir M, Williams M, Lu TT, Mansfield JC, Lamb CA, Feagan BG, Panes J, Salas A et al.. (2014) Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial. Lancet, 384 (9940): 309-18. [PMID:24814090]

16. Vermeire S, Sandborn WJ, Danese S, Hébuterne X, Salzberg BA, Klopocka M, Tarabar D, Vanasek T, Greguš M, Hellstern PA et al.. (2017) Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet, 390 (10090): 135-144. [PMID:28527704]

17. Yazbeck R. (2010) Teduglutide, a glucagon-like peptide-2 analog for the treatment of gastrointestinal diseases, including short bowel syndrome. Curr. Opin. Mol. Ther., 12 (6): 798-809. [PMID:21154171]