Inflammatory bowel disease: Therapeutic limitations and prospective of the stem cell therapy

Table 1 Drugs used for treating inflammatory bowel disease patients, their side effects and mode of action

Drug	Indications	Side effects	Target or mechanism of action
Anti-inflammatory agents
5-ASA	Mild to moderate IBD	Renal toxicity[110,111]	By scavenging of ROS[35]
Steroids	Mild to moderate IBD	Cataracts, bone loss, easy bruising, muscle weakness, and thrush, weight gain, swelling, high blood sugar, increased risk of infection, psychosis, nausea, vomiting, loss of appetite, heartburn, trouble sleeping, increased sweating, or acne[36,37]	By decreasing inflammation via suppression of the migration of polymorphonuclear leukocytes and reversing increased capillary permeability. Also, by suppressing the immune system by reducing the activity and the volume of the immune system[37]
Thiopurines	Mild to moderate IBD	Hepatotoxicity, pancreatitis, myelotoxicity[42]	Either by blocking of the TcR signaling pathway, or by 6-TG inhibition of purine synthesis (suspected)
Methotrexate	CD, rheumatoid arthritis, psoriasis	Hepatotoxicity, ulcerative stomatitis, leukopenia, predisposition to infection, nausea, abdominal pain, fatigue, fever, dizziness, acute pneumonitis, pulmonary fibrosis, kidney failure[112]	By blocking the binding of interleukin 1beta to interleukin 1 receptor[113]
Biologics
TNF-alpha antagonists
Infliximab	CD[114], UC, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease	Nausea, heartburn, headache, runny nose, white patches in mouth, vaginal yeast infection, flushing[115]	By binding to TNF-alpha and preventing its interaction with the receptor
Adalimumab	Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, CD, UC, psoriasis, hidradenitis suppurativa, uveitis, and juvenile idiopathic arthritis	Injection site pain, URTI, increased creatine, phosphokinase, headache, rashes, sinus infection, nausea, UTI, abdominal pain, Flulike syndrome, hyperlipidemia, back pain, high cholesterol, blood in the urine, hypertension, increased alkaline phosphatase[116]	By binding with TNF-alpha and blocking its interaction with the p55 and p75 cell surface TNF receptors; causes lysis of cells with surface TNF in the presence of complement
Certolizumab pegol	Rheumatoid arthritis[58,60]	Cough, sore throat, stuffy or runny nose, burning or painful frequent urination, joint pain[60,117]	By binding to soluble and membrane-bound TNF-alpha, inhibiting its proinflammatory actions
Golimumab	UC[57]	Severe infections, opportunistic infections, reactivation of tuberculosis, malignancies, heart failure, autoimmunity, and demyelinating disorders[57]	By binding with both soluble and transmembrane forms of TNF-alpha
Integrin receptor antagonists
Natalizumab	CD, multiple sclerosis	Fatigue, allergic reactions with a low risk of anaphylaxis, headache, nausea, colds, occasional exacerbation of CD[118]	By inhibiting alpha 4 integrin
Vedolizumab	CD, UC[119]	Common cold runny or stuffy nose, sinus pain, headache, joint pain, nausea, fever, infections of the nose and throat, tiredness, fatigue etc.	By inhibiting alpha4 beta7 integrin[119]
Interleukin antagonist
Ustekimumab	CD, plaque psoriasis.	Increased risk of infections and developing cancer	By blocking IL-23[120]

5-ASA: 5-Aminosalicylic acid; IBD: Inflammatory bowel disease; ROS: Reactive oxygen species; 6-TG: 6-Thioguanine; URTI: Upper respiratory tract infection; UTI: Urinary tract infection; CD: Crohn’s disease; UC: Ulcerative colitis.