Article Figures & Data
Figures
- Figure 1.
A simplified approach to “step-wise” treatment of inflammatory bowel disease. 5-ASA, 5-aminosalicylic acid.
- Figure 2.
A simplified approach to azathioprine (AZA) metabolism. Thiopurine methyltransferase (TPMT) breaks down 6-mercaptopurine (6-MP) into the hepatotoxic metabolite 6-methylmercaptopurine (6-MMP). Besides TPMT metabolism, there are 2 other major pathways from 6-MP that should be considered. One is driven by the hypoxanthine phosphoribosyl transferase (HPRT) enzyme, leading to 6-thioguanine nucleotide (6-TGN), the metabolite responsible for both the therapeutic benefit in inflammatory bowel disease and myelosuppression. The other pathway is driven by xanthine oxidase (XO), leading to production of 6-thiouric acid (6-TU), an inactive metabolite. 6-TIMP, 6-thioinosine monophosphate.
Tables
- Table 1. Summary of Advanced Agents in Inflammatory Bowel Disease: Mechanisms of Action, Side Effects, and Long-term Monitoring
Category Examples (US Brand Names) Mechanism of Action Side Effects Monitoring Immunomodulator therapy Thiopurines
Azathioprine (Imuran, Azasan)
6-Mercaptopurine (Purinethol)Interferes with de novo synthesis of purine ribonucleotides, leading to decrease in immune cell production8 Common:
Gastrointestinal: nausea, vomiting, abdominal pain, hepatotoxicity, pancreatitis
Allergic: fever, rash, arthralgia
Hematologic: leukopeniaCBC and LFTs every 4–12 weeks Uncommon:
Hematologic: lymphoma, nonmelanoma skin cancerMethotrexate (Rheumatrex, Trexall) Multiple anti-inflammatory effects, including blocking production of IL-1, IL-2, IL-6, IL-816 Common:
General: stomatitis, hair loss
Gastrointestinal: nausea, diarrhea
Hematologic: leukopenia
Obstetric: teratogen, abortifacientLFT every 1–3 months, periodic CBC Uncommon:
Gastrointestinal: hepatic fibrosis
Pulmonary: interstitial pneumonitisBiologic Therapy Anti-TNF-α
Infliximab (Remicade)
Adalimumab (Humira)
Certolizumab pegol (Cimzia)Neutralization of TNF-α, along with specific molecular effects, leading to reduced immune response25 Common:
General: intravenous infusion reaction (chest pain, dyspnea, rash, hypotension), fatigue
Dermatologic: subcutaneous injection site reaction and pain
Rheumatologic: polyarthralgia
Infectious disease, particularly granulomatousAnnual tuberculosis testing, periodic LFTs, CBC, and renal function tests Anti-α-4 integrin
Natalizumab (Tysabri)Blocks integrin, which reduces leukocyte adhesion and migration into inflamed gut22,23 Uncommon:
Hematologic: lymphoma, hepatosplenic T-cell lymphoma (particularly in young males taking biologics and immunomodulators)
Rheumatologic: antinuclear antibody formation, anti-double stranded DNA
Neurologic: demyelination, polyneuropathy, progressive multifocal leukoencephalopathy (natalizumab)CBC, complete blood count; IL, interleukin; LFT, liver function test; TNF, tumor necrosis factor.
- Table 2. Examples of Doses and Cost per Dose of Common Advanced Therapies for Inflammatory Bowel Disease
Examples by Category (US Brand Names) Dose* Cost per Dose ($)† Immunomodulator therapy Thiopurines Azathioprine (Imuran, Azasan) 100 mg daily (generic, supply of 50 tablets) 262.16 Methotrexate (Rheumatrex, Trexall) 25 mg/mL per week (generic, supply 2 mL solution) 8.59 Biologic therapy Anti-tumor necrosis factor-α Infliximab (Remicade) 100 mg intravenous every 8 weeks (brand, one dose) 974.27 Adalimumab (Humira) 40 mg subcutaneous every 2 weeks (brand, 2 doses) 2809.30 Certolizumab pegol (Cimzia) 400 mg subcutaneous once monthly (brand, one dose) 2664.00 Anti-α-4 integrin Natalizumab (Tysabri) 300 mg intravenous once monthly (brand, one dose) 5296.50 ↵* Doses reflect only common doses and should not be used to determine starting doses.
↵† Prices obtained from Medi-Span database (www.medispan.com) in October 2013.
