Details of the Drug

General Information of Drug (ID: DMSA8RU)

• Drug Name: Abatacept
• Synonyms: Orencia (TN)

Indication

Disease Entry	ICD 11	Status	REF
Rheumatoid arthritis	FA20	Approved	[1], [2], [3]

• Therapeutic Class: Antirheumatic Agents
• Sequence:
  MHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTF
  LDDSICTGTSSGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPC
  PDSDQEPKSSDKTHTSPPSPAPELLGGSSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED
  PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA
  PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN
  YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
• ADMET Property:
  Clearance: The sytemic clearance of drug is 0.28 mL/h/kg [4]
  Elimination: The drug is excreted via kidney and liver [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 16.7 (12 - 23) days [5]
  Vd: The volume of distribution (Vd) of drug is 0.07 L/kg [4]
• Cross-matching ID:
  DrugBank ID: DB01281
  TTD ID: D0EW4L

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Activation B7-1 antigen (CD80)	TTFZDNP	CD80_HUMAN	Binder	[6]
T-lymphocyte activation antigen CD86 (FUN1)	TTHGXBU	CD86_HUMAN	Binder	[6]

Molecular Expression Atlas of This Drug

• The Studied Disease: Rheumatoid arthritis
• ICD Disease Classification: FA20

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Activation B7-1 antigen (CD80)	DTT	CD80	6.87E-07	-0.12	-0.3

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Abatacept

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Upadacitinib	DM32B5U	Major	Additive immunosuppressive effects by the combination of Abatacept and Upadacitinib.	Rheumatoid arthritis [FA20]	[13]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Abatacept and Canakinumab.	Rheumatoid arthritis [FA20]	[14]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Abatacept and Rilonacept.	Rheumatoid arthritis [FA20]	[14]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Abatacept and Golimumab.	Rheumatoid arthritis [FA20]	[15]

Coadministration of a Drug Treating the Disease Different from Abatacept (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Abatacept and Roflumilast.	Asthma [CA23]	[13]
Denosumab	DMNI0KO	Moderate	Additive immunosuppressive effects by the combination of Abatacept and Denosumab.	Low bone mass disorder [FB83]	[16]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Abatacept and Tecfidera.	Multiple sclerosis [8A40]	[17]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Abatacept and Siponimod.	Multiple sclerosis [8A40]	[18]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Abatacept and Fingolimod.	Multiple sclerosis [8A40]	[19]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Abatacept and Ozanimod.	Multiple sclerosis [8A40]	[13]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Abatacept and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[20]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6891).
• [2] Emerging drugs for idiopathic thrombocytopenic purpura in adults. Expert Opin Emerg Drugs. 2008 Jun;13(2):237-54.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
• [5] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] Selective modulation of T-cell co-stimulation: a novel mode of action for the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2009 May-Jun;27(3):510-8.
• [7] Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011 Apr 29;332(6029):600-3.
• [8] US patent application no. 2004,0171,123, Albumin fusion proteins.
• [9] A phase 1 study of AS1409, a novel antibody-cytokine fusion protein, in patients with malignant melanoma or renal cell carcinoma. Clin Cancer Res. 2011 Apr 1;17(7):1998-2005.
• [10] Clinical pipeline report, company report or official report of Heat Biologics.
• [11] Phase I/II study of galiximab, an anti-CD80 antibody, for relapsed or refractory follicular lymphoma. J Clin Oncol. 2005 Jul 1;23(19):4390-8.
• [12] ClinicalTrials.gov (NCT03198052) HER2/Mesothelin/Lewis-Y/PSCA/MUC1/PD-L1/CD80/86-CAR-T Cells Immunotherapy Against Cancers
• [13] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [14] Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
• [15] Product Information. Orencia (abatacept). Bristol-Myers Squibb, Princeton, NJ.
• [16] Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
• [17] Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
• [18] Cerner Multum, Inc. "Australian Product Information.".
• [19] Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
• [20] Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.