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Ankylosing spondylitis

Disease ID:1196
Name:Ankylosing spondylitis
Associated with:0 target
14 immuno-relevant ligands
Synonyms
Bekhterev syndrome | Marie-Strumpell disease
Description
A bone inflammation disease that causes inflammation in the joints of the spine and pelvis.
Database Links
Disease Ontology: DOID:7147

Targets

No target related data available for Ankylosing spondylitis

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
adalimumab
Immuno Disease Comments: Anti-TNFα monoclonal antibody therapy approved for ankylosing spondylitis.
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 [7]. The EMA marketing authorisation for adalimumab Trudexa® was withdrawn at the request of the marketing authorisation holder. | View clinical data
filgotinib
Immuno Disease Comments: A Phase 2 clinical candidate for ankylosing spondylitis (see NCT03117270).
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 [5].

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
etoricoxib
Immuno Disease Comments: Selective COX2 inhibitor approved for the treatment of many inflammatory conditions including ankylosing spondylitis.
Clinical Use: Used in the treatment of rheumatoid arthritis, osteoarthritis, chronic lower back pain, ankylosing spondylitis, acute pain and gout. There is no information regarding approval for medicinal use of etoricoxib on the US FDA website. Individual national agencies may have granted marketing approval. | View clinical data
flurbiprofen
Immuno Disease Comments: Approved NSAID used for many inflammatory conditions including ankylosing spondylitis.
Clinical Use: Flurbiprofen is approved to treat the pain and inflammation associated with rheumatic diseases and other musculoskeletal disorders, as well as dysmenorrhoea, migraine and as postoperative analgesia. | View clinical data
IL-17A
Immuno Disease Comments: Approved therapy for systemic ankylosing spondylitis.
naproxen
Immuno Disease Comments: Approved NSAID used for ankylosing spondylitis.
Clinical Use: Used in the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, bursitis, and acute gout. Also used in pain relief in the treatment of primary dysmenorrhea. | View clinical data
sulindac
Immuno Disease Comments: Approved drug for ankylosing spondylitis.
Clinical Use: For acute relief or long term use in osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute painful shoulder and acute gouty arthritis. | View clinical data
golimumab
Immuno Disease Comments: An anti-TNFα therapy approved for ankylosing spondylitis.
Clinical Use: Used in adults with various inflammatory conditions [12] e.g. moderate to severe active rheumatoid arthritis [8], active psoriatic arthritis, active ankylosing spondylitis and moderate to severe ulcerative colitis. | View clinical data
etanercept
Immuno Disease Comments: Approved drug for AS.
Clinical Use: Used to treat severe active rheumatoid arthritis in adults, severe juvenile idiopathic arthritis, ankylosing spondylitis, and severe plaque psoriasis. | View clinical data
sarilumab
Immuno Disease Comments: Clinical trial in ankylosing spondylitis was terminated.
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 [3]. 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
secukinumab
Immuno Disease Comments: Approved therapeutic for ankylosing spondylitis.
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 [10-11] 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 [4]. | View clinical data
risankizumab
Immuno Disease Comments: Phase 2 proof of concept trial in ankylosing spondylitis has been completed.
Clinical Use: Results from the first-in-human proof-of-concept trial in patients with psoriasis were reported by Krueger et al. in 2015 [9]. Phase 3 trial results in psoriasis patients were published in 2018 [6]. FDA and EMA approvals were granted in 2019 and it is also approved in Japan and Canada. Risankizumab therapy is indicated for patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy (Japan's authorisation additionally includes treatment of generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis). Investigations are ongoing in other autoinflammatory conditions. Click here to link to ClinicalTrials.gov's full list of risankizumab trials. | View clinical data
MRL-367
Immuno Disease Comments: Experimental compound with predicted application in ankylosing spondylitis.
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 [2]. | View biological activity
MRL-248
Immuno Disease Comments: Experimental compound with predicted application in ankylosing spondylitis.
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 [2]. | 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. 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]

3. 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]

4. 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]

5. 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

6. Gordon KB, Strober B, Lebwohl M, Augustin M, Blauvelt A, Poulin Y, Papp KA, Sofen H, Puig L, Foley P et al.. (2018) Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet, 392 (10148): 650-661. [PMID:30097359]

7. 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]

8. Kay J, Matteson EL, Dasgupta B, Nash P, Durez P, Hall S, Hsia EC, Han J, Wagner C, Xu Z et al.. (2008) Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: a randomized, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum, 58 (4): 964-75. [PMID:18383539]

9. 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]

10. 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]

11. 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]

12. Zhou H, Jang H, Fleischmann RM, Bouman-Thio E, Xu Z, Marini JC, Pendley C, Jiao Q, Shankar G, Marciniak SJ et al.. (2007) Pharmacokinetics and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis. J Clin Pharmacol, 47 (3): 383-96. [PMID:17322150]