Comparative tolerability of treatments for inflammatory bowel disease

Despite limited understanding of therapeutic aetiopathogenesis of ulcerativ e colitis and Crohn's disease, there is a strong evidence base for the effi cacy of pharmacological and biological therapies. It is equally important t o recognise toxicity of the medical armamentarium for inflammatory bowel di sease (IBD). Sulfasalazine consists of sulfapyridine linked to 5-aminosalicylic acid (5- ASA) via an azo bond. Common adverse effects related to sulfapyridine 'into lerance' include headache, nausea, anorexia, and malaise. Other allergic or toxic adverse effects include fever, rash, haemolytic anaemia, hepatitis, pancreatitis, paradoxical worsening of colitis, and reversible sperm abnorm alities. The newer 5-ASA agents were developed to deliver the active ingredient of s ulfasalazine while minimising adverse effects. Adverse effects are infreque nt but may include nausea, dyspepsia and headache. Olsalazine may cause a s ecretory diarrhoea. Uncommon hypersensitivity reactions, including worsenin g of colitis, pancreatitis. pericarditis and nephritis, have also been repo rted. Corticosteroids are commonly prescribed for treatment of moderate to severe IBD. Despite short term efficacy. corticosteroids have numerous adverse ef fects that preclude their long term use. Adverse effects include acne, flui d retention, fat redistribution. hypertension, hyperglycaemia, psyche-neuro logical disturbances, cataracts. adrenal suppression, growth failure in chi ldren, and osteonecrosis. Newer corticosteroid preparations offer potential for targeted therapy and less corticosteroid-related adverse effects. Azathioprine and mercaptopurine are associated with pancreatitis in 3 to 15 % of patients that resolves upon drug cessation. Bone marrow suppression is dose related and may be delayed. The adverse effects of methotrexate include nausea, leucopenia and, rarely, hypersensitivity pneumonia or hepatic fibrosis. Common adverse effects of cyclosporin include nephrotoxicity, hypertension, headache, gingival hyperp lasia, hyperkalaemia, paresthesias, and tremors. These adverse effects usua lly abate with dose reduction or cessation of therapy. Seizures and opportu nistic infections have also been reported. Antibacterials are commonly employed as primary therapy for Crohn's disease . Common adverse effects of metronidazole include nausea and a metallic tas te. Peripheral neuropathy can occur with prolonged administration. Ciproflo xacin and other antibacterials may be beneficial in those intolerant to met ronidazole. Newer immunosuppressive agents previously reserved for transplant recipient s are under investigation for IBD. Tacrolimus has an adverse effect profile similar to cyclosporin, and may cause renal insufficiency. Mycophenolate m ofetil, a purine synthesis inhibitor, has primarily gastrointestinal advers e effects. Biological agents targeting specific sites in the immunoinflammatory cascad e are now available to treat IBD. infliximab, a chimeric antibody targeting tumour necrosis factor-a has been well tolerated in clinical trials and ea rly postmarketing experience. Additional trials are needed to assess long t erm adverse effects.