Systemic scleroderma

Disease ID:1036
Name:Systemic scleroderma
Associated with:1 target
2 immuno-relevant ligands
Synonyms
Scleroderma, familial progressive | Systemic sclerosis
Description
A complex heterogeneous fibrosing autoimmune disorder characterised by extensive fibrosis, vasculopathy, and immune dysfunction.
Database Links
Disease Ontology: DOID:418
OMIM: 181750
Orphanet: ORPHA90291

Targets

NLRP1

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
brentuximab vedotin
Immuno Disease Comments: Phase 1/2 clinical candidate for systemic sclerosis- see NCT03222492 and NCT03198689
Clinical Use: Brentuximab vedotin is an anti-neoplastic agent used in the treatment of Hodgkin's lymphoma [5] and systemic anaplastic large cell lymphoma. Several clinical trials are evaluating the combination of brentuximab vedotin with immune checkpoint inhibitors, to assess any synergistic effects as a result of dual targeting. Checkpoint inhibitors being investigated in this way include and (both anti-PD-1), and (anti-CTLA4). Brentuximab vedotin + pembrolizumab (NCT02684292) and brentuximab vedotin + nivolumab (NCT03138499) are both Phase 3 studies in patients with relapsed/refractory classical Hodgkin's lymphoma.

Expanded approvals:
In November 2017, the FDA approved brentuximab vedotin for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, following review of results from the Phase 3 ALCANZA trial (NCT01578499) [2]. In March 2018, the FDA approved the use of brentuximab vedotin for the treatment of patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy. This expansion was based on results from the ECHELON-1 clinical trial (NCT01712490) [1,6]. | View clinical data
Bioactivity Comments: Detailed information contained in the covering patent [3] describes in vitro and in vivo activity of the invention, which supports its anti-CD30 action. However, no affinity data is provided for the interaction between the antibody and its molecular target. | View biological activity
ajulemic acid
Immuno Disease Comments: A Phase 3 multicenter trial to evaluate AJA's safety and efficacy in SSc has recently been initiated- see NCT03398837
Clinical Use: Ajulemic acid (research code JBT-101) is being evaluated as a treatment for systemic lupus erythematosus (SLE) in Phase 2 clinical trial NCT03093402.
It was also more effective in reducing chronic neuropathic pain than placebo in a Phase 2 clinical trial [4]. | View clinical data

References

Show »

1. Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illés Á, Picardi M et al.. (2018) Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N. Engl. J. Med., 378 (4): 331-344. [PMID:29224502]

2. FDA. FDA approves Brentuximab vedotin for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma. Accessed on 10/11/2017. Modified on 10/11/2017. fda.gov, https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm584543.htm?utm_campaign=Oncology%2011%2F9&utm_medium=email&utm_source=Eloqua&elqTrackId=06d11c937bec44c79cd3d453daecb608&elq=4d1b00c5aad64538a4ce8e687b3f3786&elqaid=1289&elqat=1&elqCampaignId=770

3. Francisco JA, Risdon G, Wahl AF, Siegall C. (2006) immunotherapy; fusion proteins; antitumor agents; for treatment and prevention of hodgkin's disease. Patent number: US7090843. Assignee: Seattle Genetics, Inc. Priority date: 09/12/2014. Publication date: 15/08/2006.

4. Karst M, Salim K, Burstein S, Conrad I, Hoy L, Schneider U. (2003) Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. JAMA, 290 (13): 1757-62. [PMID:14519710]

5. Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A et al.. (2015) Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 385 (9980): 1853-62. [PMID:25796459]

6. Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. (2013) Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol., 14 (13): 1348-56. [PMID:24239220]