A. Optimization of the treatment with immunosuppressants and biologics in inflammatory bowel disease.

Many placebo controlled trials and meta-analyses evaluatedthe efficacy of different drugs for the treatmentof inflammatory bowel disease (IBD), including immunosuppressantsand biologics. Their use is indicated inmoderate to severe disease in non responders to corticosteroidsand in steroid-dependent patients, as inductionand maintainance treatment. Infliximab, as well ascyclosporine, is considered a second line therapy in thecase of severe ulcerative colitis, or non-responders to intravenouscorticosteroids. An adequate dosage and durationof therapy with thiopurines should be reached beforeevaluating their efficacy. Methotrexate is a valid optionin patients with Crohn’s disease but its use is confined topatients who are intolerant or non-responders to thiopurines.Evidence for the use of methotrexate in ulcerativecolitis is insufficient. The use of thalidomide and mycophenolatemofetil is not recommended in patients withinflammatory bowel disease, these treatments could beconsidered in case of failure of all other therapeutic options.In patients with moderately active ulcerative colitis,refractory to thiopurines, the use of tacrolimus is consideredan alternative to biologics. An increase of the doseor a decrease in the interval of administration of biologicaltreatment could be useful in the presence of an incompleteclinical response. In the case of primary failureof an anti-tumor necrosis factor alpha a switch to anotherone should be considered. Data on the efficacy of combinationtherapy are up to now insufficient to considerthis strategy in all IBD patients. The final outcome of thetreatment should be considered the clinical remission,with mucosa healing, and not the clinical response. Theevaluation of serum concentration of thiopurine methyltransferase activity, thiopurine metabolites, biologic serumlevels and antibiologic antibodies could be useful forthe management of the treatment but it has not beenroutinely applied in clinical practice. The evidence of highrisk development of lymphoma and cutaneous malignanciesshould be considered in patients treated with immunosuppressantsand biologics for a long period.