Pharmacologic therapy for inflammatory bowel disease refractory to steroids

Figures & data

Figure 1 Optimizing thiopurines.

Abbreviations: IBD, inflammatory bowel disease; 6-TGN, 6-thioguanine; 6-MMP, 6-methylmercaptopurine; TP, thiopurine; TPMT, thiopurine-S-methyltransferase.

Table 1 Adverse effects of immunomodulators

Drug	Type of adverse events	Percentage of patients
AZA/6-MP	Allergic reactions: malaise, rash, fever, pancreatitis, hepatitis	5–10
	Bone marrow suppression: leukopenia	2–15
	Infections	0.3–7.4
	Liver toxicity (cholestasis, endothelial damage, portal hypertension, hepatic peliosis, venous occlusion)	3–10
	Malignancies (lymphomas, non-melanoma skin cancer, leukemia, cervical cancer)	Lymphoma (OR 2–4.18)
MTX	Digestive intolerance	13
	Pneumonitis	2.7
	Bone marrow toxicity	3
	Liver enzyme alterations	10
	Liver fibrosis	5
	Teratogenicity	100
CsA	Hypertension	15–30
	Nephrotoxicity	5
	Seizures	4
	Headache	20
	Paresthesias	50
	Tremor, muscle pain	10–15
	Infections	6–15
	Hypomagnesemia/hypercholesterolemia	30–40
Tacrolimus	Hypertension, hyperglycemia	2–3
	Paresthesias, tremor, headache	10–30
	Renal failure (generally reversible)	6–14
	Gastrointestinal intolerance	7–50
	Opportunistic infections	8
MMF	Diarrhea	30
	Histological changes similar to those of graft versus host disease
Thalidomide	Neurological toxicity (neuropathy)	30–50
	Teratogenicity	100

Abbreviation: AZA, azathioprine; 6-MP, mercaptopurine; MTX, methotrexate; CsA, cyclosporine, MMF, Mycophenolato mofetil. OR, odds ratio.

Table 2 Drugs, doses, formulations, regimens, and half-life of biologic therapy

Drug	Dosage form	Pharmaceutical presentation	Dose and schedule	Half-life
Infliximab (Remicade^®)	Intravenous	Vial 100 mg	Induction: 5 mg/kg at 0/2/6 weeks Maintenance: every 8 weeks Induction: 5–10 mg/kg, 6–4 weeks	7.7–9.5 days
Adalimumab (Humira^®)	Subcutaneous	Drug pen 40 mg	Induction: 160/80/40 mg at 0/2/4 weeks Maintenance: 40 mg/15 days Induction: 40 mg/every other week	2 weeks (10–20 days)
Golimumab (Simponi^®)	Subcutaneous	Drug pen 50 mg	Induction 200/100 mg at 0/2 weeks Maintenance: <80 kg 50 mg/4 weeks ≥80 kg 100 mg/4 weeks	2 weeks
Certolizumab (Cimzia^®)	Subcutaneous	Drug pen 200 mg	Induction: 400 mg at 0/2/4 weeks Maintenance: 400 mg/4 weeks	14 days
Ustekinumab (Stelara^®)	Subcutaneous	Drug pen 45 mg	Not defined in CD	21.6 days
Vedolizumab (Entyvio^®)	Intravenous	Vial 300 mg	Induction: 300 mg at 0/2/6 weeks Maintenance: 8 weeks	6 weeks

Abbreviation: CD, Crohn’s disease.

Figure 2 Optimization strategy for non-responders to anti-TNFα.

Abbreviations: ADAs, anti-drug antibodies; TNFα, tumor necrosis factor alpha.

Figure 3 Therapheutic algorithm in Crohn’s Disease.

Note: *Indicates low drug level without ADA.
Abbreviations: ADAs, anti-drug antibodies; CDAI, Crohn’s Disease Activity Index; IMM, immunomodulator; TDM, therapeutic drug monitoring; TNFα, tumor necrosis factor alpha.

Figure 4 Therapeutic algorithm in ulcerative colitis.

Abbreviations: IV, intravenous; TNFα, tumor necrosis factor alpha; UC, ulcerative colitis; TPs, thiopurines.

Figure 5 Therapeutic algorithm in severe ulcerative colitis.

Abbreviations: CsA, cyclosporine; IV, intravenous; IFX, infliximab; TPs, thiopurines; UC, ulcerative colitis.