Infliximab Azathioprine

Maintenance of remission of Crohn s disease may be achieved with oral or topical aminosalicylate derivatives, immunosuppressants (such as azathioprine, 6-mercaptopurine, and methotrexate), or infliximab. 

Colitis Mesalamine 2.4-A.8 g/day or sulfasalazine 4-6 g/day orally If no response to mesalamine or sulfasalazine Prednisone 40-60 mg/day orally or Infliximab 5 mg/kg IV at weeks 0, 2, and 6 Taper mesalamine to 1.6-2.4 g/day or sulfasalazine 2-4 g/day orally If prednisone or infliximab were required Taper prednisone as soon as possible Give infliximab 5 mg/kg IV every 8 weeks Consider adding azathioprine or 6-MP 1.5-2.5 mg/kg per day orally... 

Oral corticosteroids may be used for patients who are unresponsive to sulfasalazine or mesalamine. Prednisone doses of 40 to 60 mg per day (or equivalent) are recommended.1 Azathioprine or 6-MP is used for patients unresponsive to corticosteroids or those who become steroid-dependent. Over a 12-month period, these agents have been shown to reduce the relapse rate to 36% versus 59% seen with placebo.1 Infliximab 5 mg/kg may also be used for patients who are unresponsive to conventional oral therapies and may reduce the need for colectomy after 3 months of treatment.35... 

Immunosuppressants such as azathioprine or 6-mercaptopurine can be used for unresponsive patients or those who develop corticosteroid dependency. Remission may be maintained in up to 58% of patients after 5 years of treatment.1,25 Intermittent infliximab dosing (5 mg/kg IV every 8 weeks) may be used to maintain disease remission and reduce the need for corticosteroids in patients with moderate to severe UC. Colectomy is an option for patients with progressive disease who cannot be maintained on drug therapy alone. 

Patients with CD are at high risk for disease relapse after induction of remission. Within 2 years, up to 80% of patients suffer a relapse therefore, most patients should be evaluated for indefinite maintenance therapy. Maintenance of remission of CD may be achieved with oral or topical aminosalicylate derivatives, immunosuppressants (such as azathioprine, 6-mercaptopurine, and methotrexate), or infliximab. 

The aminosalicylates, azathioprine, 6-MP, and infliximab are all viable options for treatment and maintenance of IBD in pediatric patients. Use of immunosuppressive therapy or infliximab may help reduce overall corticosteroid exposure. 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

Azathioprine is effective in preventing relapse of ulcerative colitis for periods exceeding 4 years. However, 3 to 6 months may be required for beneficial effect. For patients who initially respond to infliximab, continued administration of 5 mg/kg every 8 weeks as maintenance therapy is an alternative for steroid dependent patients. 

In the majority of patients, active Crohn s disease is treated with sulfasalazine, mesalamine derivatives, or steroids, although azathioprine, mercap-topurine, methotrexate, infliximab, and metronidazole are frequently used. 

Although the published data are not consistent, there is evidence to suggest that azathioprine, mercaptopurine, methotrexate, infliximab, and adalimumab are effective in maintaining remission in Crohn s disease. 

The present primary mode of therapy for these diseases involves the use 5-amino-salicylate (5-ASA) products. Often patients require additional medications, including corticosteroids, to help induce remission and various immune modulators, such as azathioprine, 6-mercaptopurine or methotrexate, to maintain remission. In Crohn s disease certain antibiotics, such as metronidazole and ciprofloxacin, and infliximab Remi-cade), an anti-tumor necrosis factor-a(TNFa) antibody, also have been used. The pharmacology of antibiotics, immunosuppressive drugs, and corticosteroids is discussed in Chapters 43,57, and 60, respectively. 

When added to methotrexate background therapy, cyclosporine, chloroquine, hydroxychloroquine, leflunomide, infliximab, adalimumab, rituximab, and etanercept have all shown improved efficacy. In contrast, azathioprine, auranofin, or sulfasalazine plus methotrexate results in no additional therapeutic benefit. Other combinations have occasionally been used, including the combination of intramuscular gold with hydroxychloroquine. 

Autoreactive tissue disorders (autoimmune diseases)2 Prednisone, cyclophosphamide, methotrexate, interferon-a and -3, azathioprine, cyclosporine, infliximab, etanercept, adalimumab Often good, variable... 

Steroids do not have a role in the maintenance of remission with ulcerative cohtis because they are ineffective. Steroids should he gradually withdrawn after remission is induced (over 3 to 4 weeks). If they are continued, the patient will he exposed to steroid side effects without likelihood of benefits. Azathioprine is effective in preventing relapse of ulcerative colitis for periods exceeding 4 years. However, 3 to 6 months may be required for beneficial effect. For patients who initially respond to infliximab, continued administration of 5 mg/kg every 8 weeks as maintenance therapy is an alternative for steroid dependent patients. 

Other drugs that are useful for treatment of Crohn s disease include metronidazole (for perineal disease), azathioprine or mercaptopurine (for inadequate response or to reduce steroid dosage), cyclosporine (for refractory disease), and infliximab for refractory or fistulizing disease. 

Drug intolerance often limits the usefulness of agents used to treat IBD. Many patients receiving sulfasalazine, mesalamine, corticosteroids, metronidazole, azathioprine, mercaptopurine, or infliximab experience some undesired effects. In some cases, these adverse effects can be significant and require discontinuation of the therapy. Knowledge of the common or important adverse reactions will assist in avoiding or minimizing their effects. 

RoblinX, Serre-Debeauvais F, Phelip J-M, BessardG, BonazB. Drug interaction between infliximab and azathioprine in patients with Crohn s disease. Aliment Pharmacol TTi r (2003) 18, 917-25. 

Live vaccines should not be given to patients undergoing treatment with infliximab. Serious infection and neutropenia is predicted to occur if infliximab is given with anakinra. Infliximab may increase serum levels of azathioprine metabolites, and a rare T-cell lymphoma has been reported in adolescents and young adults treated with infliximab and also given azathioprine or mercaptopurine. Serum levels of infliximab appear to be unaffected by aminosalicylates, corticosteroids, ciprofloxacin or metronidazole. 

Systemic corticosteroids are required for cases of anterior uveits that are refractory to eyedrops and for cases of intermediate and posterior uveitis because eyedrops cannot adequately penetrate deep into the eye. The initial corticosteroid dose is 40 mg/day of prednisone equivalent, which is adjusted according to the response to therapy. Corticosteroid-sparing alternatives are often considered for sarcoid uveitis because of the toxicity of systemic corticosteroids. Methotrexate (21), azathioprine (22), leflunomide (23), and infliximab (24) have been used for this purpose. 

If the corticosteroid dose cannot be tapered to the 10 mg/day of prednisone equivalent over the first several months, alternative medications should be considered. Most of these agents are not effective alone but may be corticosteroid sparing. Such agents have included methotrexate (170), hydroxychloroquine (168,171), chloroquine (168,171), azathioprine (172), cyclosporine (172,173), cyclophosphamide (170,174), and infliximab (175). Although smdies of these agents have for the most part involved uncontrolled case series, methotrexate and cyclophosphamide appears to be the most efficacious. Radiation therapy has been used successfully in refractory cases (176). 

Abbreviations. increase decrease oo, restrict dietary calcium F, high fluid intake CED, corticosteroid eye drops CP, cycloplegics C, corticosteroids— usually 20 to 40 mg prednisone equivalent/day M, methotrexate A, azathioprine I, infliximab CC, corticosteroid creams Cl, corticosteroid injections H, hydroxychloroquine CQ, chloroquine NSAID, non-steroidal anti-inflammatory drugs CYC, cyclophosjliamide. Source. From Ref 246. 

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