Azathioprine In Ulcerative Colitis Research Articles

Diffuse large B-cell lymphoma in a patient treated with azathioprine for ulcerative colitis: a case report.

We present a case of a 45-year-old female receiving AZA for severe ulcerative colitis for 4 years. She presented with the chief complaints of bloody stool and abdominal pain for 1 month. Through a series of investigations including colonoscopy, contrast-enhanced computed tomography scan of the abdomen and pelvis, and biopsy with immunohistochemistry; she was diagnosed to have diffuse large B-cell lymphoma of the rectum. She is currently on a chemotherapeutic regimen and is planned for surgical resection after the completion of neoadjuvant therapy. AZA is classified as a carcinogen by the International Agency for Research on Cancer. Prolonged exposure to higher doses of AZA increases the risk of developing lymphoma in IBD. Previous meta-analysis and research indicate that the risk of development of lymphoma after the use of AZA in IBD increases by about four- to six-fold, especially in older age groups. AZA may increase the susceptibility to developing lymphoma in IBD, but the benefit far outweighs the risk. Precautions must be taken in prescribing AZA in older individuals which mandates periodic screening.

Use of Azathioprine in Ulcerative Colitis: A Comprehensive Review.

Ulcerative colitis (UC) is a relapsing and remitting chronic inflammatory disease of the large intestine characterized by bloody diarrhea, abdominal pain, urgency, and tenesmus. Rapid induction and maintenance of remission are the primary goals of treatment. Azathioprine (AZA), a purine analog, has been utilized as an immuno-modulator to maintain remission in UC. AZA has been used for a long time, but there is still controversy about its effectiveness, drug interactions, and side effects in people with UC. We conducted a comprehensive analysis of the literature and present a detailed insight into the role of AZA in patients with UC.

BI28: Immune reconstitution syndrome following discontinuation of long‐term azathioprine for ulcerative colitis

BI28: Immune reconstitution syndrome following discontinuation of long‐term azathioprine for ulcerative colitis

Recurrent acute pancreatitis induced by 5-ASA and azathioprine in ulcerative colitis

Drug-induced acute pancreatitis (DIAP) is an often-neglected entity where the disorder is the consequence of the toxic effects of various agents applied to treat potentially life-threatening conditions, such as inflammatory bowel disease. Here, we present the case of a male patient with ulcerative colitis with a history of two episodes of recurrent acute pancreatitis. After excluding other potential causes, we suspected DIAP since the patient received 5-aminosalycilate (5-ASA) prior to the first episode and, one year later, azathioprine (AZA) prior to the second episode. The causative effect of AZA was confirmed by performing a re-challenge with a reduced dose. While both episodes of DIAP had a mild disease course, they were associated with acute relapse of ulcerative colitis. Last seen, the patient was asymptomatic. With this case, we would like to highlight the importance and diagnostic difficulties of DIAP in the background of recurrent cases when common etiological factors of acute pancreatitis are excluded.

EML4-ALK-positive non-small cell lung cancer in a patient treated with azathioprine for ulcerative colitis.

EML4-ALK-positive lung cancer is a novel cancer entity associated with light or never smoking, younger age, and adenocarcinoma with acinar or signet-ring cell type histology. Another mutation of ALK with NPM, resulting in NPM-ALK fusion mutation, was described in patients with anaplastic large cell lymphoma (ALCL). It was subsequently reported in organ transplant recipients and patiens undergoing immunosuppressive therapy. We describe a case of lung cancer in a 36-year-old nonsmoking woman with ulcerative colitis treated with azathioprine, who was diagnosed with EML4-ALK-positive, metastatic lung cancer two months postpartum. Crizotinib 300 mg/day has been effective in maintaining response after chemotherapy failed. The resemblance of this case to ALK-positive ALCL in organ transplant recipients suggests that similar mechanisms may be responsible for the development of both ALK-positive lung cancer and ALCL in patients receiving immunosuppressive therapy.

Long-term efficacy and safety of azathioprine in ulcerative colitis.

Azathioprine (AZA) is an established treatment for ulcerative colitis (UC).However, controversy exists regarding its efficacy in inducing and maintaining clinical remission, and long-term data are lacking. We studied the effectiveness of AZA in a large cohort of UC patients treated in a single center. All UC patients treated with AZA were identified from a prospective electronic database. We assessed response to therapy at 4 months and sustained clinical benefit at the last point of follow-up. We also examined predictors of response and sustained clinical benefit, as well as outcomes in those treated with AZA for >5 years. The study included 255 patients. At 4 months, 207 (81.2%) of 255 patients were still on AZA and 163 (63.9%) had responded to therapy. At the last point of follow-up 164 (64.3%) patients were still receiving AZA, of whom 154 (60.4%) achieved sustained clinical benefit. This effect was durable among 71 patients who received AZA for >5 years, with 61 (85.9%) considered to have achieved sustained clinical benefit. Twenty-six patients required admission to hospital for an exacerbation during AZA treatment, 20 patients ultimately required biologic therapy, and 21 underwent colectomy. Only two (2.8%) of 71 patients receiving AZA for >5 years needed to escalate to a biologic therapy, and only one (1.4%) required a colectomy. AZA is a safe and effective therapy in UC patients who fail 5-aminosalisylates in both the short and long term. Escalation to a biologic therapy or colectomy was unlikely among patients who were able to continue AZA therapy beyond 5 years.

PWE-098 Earlier Use Of Azathioprine In Ulcerative Colitis Does Not Alter Subsequent Need For Hospitalisation, Biologic Therapy, Or Colectomy

IntroductionAzathioprine (AZA) is an established treatment for ulcerative colitis (UC). However, controversy exists regarding its efficacy in inducing and maintaining clinical remission, particularly with the advent of biologics which, unlike...

Su1132 Earlier Use of Azathioprine in Ulcerative Colitis Does Not Alter Subsequent Need for Hospitalisation, Biologic Therapy, or Colectomy

Introduction Azathioprine (AZA) is an established treatment for ulcerative colitis (UC). However, controversy exists regarding its efficacy in inducing and maintaining clinical remission, particularly with the advent of biologics which, unlike AZA, have been tested in large, rigorously designed randomised controlled trials. We studied the effectiveness of AZA as second-line therapy after failure of 5-aminosalicylates (5-ASAs) in a large cohort of UC patients, with particular emphasis on whether its earlier use alters the natural history of the disease course. Methods All UC patients treated with AZA at our centre were identified from a prospective electronic database. We excluded individuals who had received either infliximab or ciclosporin as a bridge to AZA. The following demographic data were collected: gender, age at diagnosis, age at AZA commencement, concomitant therapy at AZA commencement, and duration of disease prior to AZA commencement. We assessed response to therapy at 4 months and remission at last point of follow-up, using physicians’ global assessment, need for hospitalisation, escalation of therapy to a biologic, or colectomy, and serious adverse events (including infections and malignancies). We examined whether earlier AZA use (within 12 months of diagnosis) reduced need for hospitalisation, biologic therapy, or colectomy. Results In total, 255 patients were included (55% male, mean age at diagnosis 36.4 years). Mean age at commencing AZA was 42.3 years. Mean disease duration prior to AZA commencement was 70 months. Concomitant therapy at AZA commencement was oral 5-ASAs in 87%, topical 5-ASAs in 22%, and oral prednisolone in 77%. At 4 months, 207 (81%) of 255 patients were still on AZA (46 had discontinued due to adverse events and 2 due to non-response), and 163 (64%) had responded to therapy. There were 165 (65%) patients still receiving AZA at last point of follow-up, of whom 153 (60%) were in remission (mean duration of therapy 64.5 months). 26 patients required admission to hospital for an exacerbation during AZA treatment, 20 patients ultimately required biologic therapy, and 21 underwent colectomy. Among 90 patients receiving AZA within 12 months of diagnosis, 21 (23%) patients experienced one of these three endpoints, compared with 29 (19%) of 154 who commenced AZA >12 months after diagnosis (p = 0.40). Serious adverse events included 6 cases of pancreatitis, 6 cases of cancer (3 non-melanoma skin cancers) and 1 case of neutropenic sepsis presenting within 1 month of AZA commencement. Conclusion AZA is a safe and effective therapy for UC patients who fail 5-ASAs, and should continue to be used prior to instituting biologic therapies. However, earlier use does not seem to alter the natural history of the disease. Disclosure of Interest None Declared.

EML4-ALK-Positive Non-Small Cell Lung Cancer in a Patient Treated with Azathioprine for Ulcerative Colitis

EML4-ALK-positive lung cancer is a novel cancer entity associated with light or never smoking, younger age, and adenocarcinoma with acinar or signet-ring cell type histology. Another mutation of ALK with NPM, resulting in NPM-ALK fusion mutation, was described in patients with anaplastic large cell lymphoma (ALCL). It was subsequently reported in organ transplant recipients and patiens undergoing immunosuppressive therapy. We describe a case of lung cancer in a 36-year-old nonsmoking woman with ulcerative colitis treated with azathioprine, who was diagnosed with EML4-ALK-positive, metastatic lung cancer two months postpartum. Crizotinib 300 mg/day has been effective in maintaining response after chemotherapy failed. The resemblance of this case to ALK-positive ALCL in organ transplant recipients suggests that similar mechanisms may be responsible for the development of both ALK-positive lung cancer and ALCL in patients receiving immunosuppressive therapy.

Azathioprine in ulcerative colitis: Why, when, how and how long to use it

AbstractUlcerative colitis (UC) is a lifelong, immune‐mediated inflammatory condition of the colonic mucosa characterized by a relapsing and remitting course. The mainstay of treatment used to be the 5‐aminosalicylates (5‐ASA) and corticosteroids. Nevertheless, some patients are unable to discontinue or reduce the steroid dosage and are exposed to a number of side effects. The efficacy of thiopurines is well proven in inflammatory bowel disease (IBD); azathioprine (AZA) is considered the first‐line immunosuppressant with a steroid‐sparing effect in UC patients with steroid dependence or resistance. Success rates of 70% occur in induction therapy with AZA and 6‐mercaptopurine (MP) in UC with a number‐needed‐to‐treat (NNT) to avoid recurrence (with AZA/MP, as compared with placebo) of 5 and absolute risk of reduction of 23%. Thus, AZA and MP are an effective therapeutic option in inducing and maintaining remission for UC patients who failed to improve or who do not tolerate 5‐ASA or corticosteroids. Drug Dev Res 72:733–738, 2011. © 2011 Wiley Periodicals, Inc.

Maintenance Treatment With Azathioprine in Ulcerative Colitis: Outcome and Predictive Factors After Drug Withdrawal

Maintenance Treatment With Azathioprine in Ulcerative Colitis: Outcome and Predictive Factors After Drug Withdrawal

Maintenance Treatment With Azathioprine in Ulcerative Colitis: Outcome and Predictive Factors After Drug Withdrawal

Maintenance Treatment With Azathioprine in Ulcerative Colitis: Outcome and Predictive Factors After Drug Withdrawal

Maintenance Treatment With Azathioprine in Ulcerative Colitis: Outcome and Predictive Factors After Drug Withdrawal

Whether the duration of maintenance treatment with azathioprine (AZA) affects the outcome of ulcerative colitis (UC) is unclear. We investigated clinical outcomes and any predictive factors after withdrawal of AZA in UC. In this multicenter observational retrospective study, 127 Italian UC patients, who were in steroid-free remission at the time of withdrawal of AZA, were followed-up for a median of 55 months or until relapse. The frequency of clinical relapse or colectomy after AZA withdrawal was analyzed according to demographic, clinical, and endoscopic variables. After drug withdrawal, a third of the patients relapsed within 12 months, half within 2 years and two-thirds within 5 years. After multivariable analysis, predictors of relapse after drug withdrawal were lack of sustained remission during AZA maintenance (hazard ratio, HR 2.350, confidence interval, CI 95% 1.434-3.852; P=0.001), extensive colitis (HR 1.793, CI 95% 1.064-3.023, P=0.028 vs. left-sided colitis; HR 2.024, CI 95% 1.103-3.717, P=0.023 vs. distal colitis), and treatment duration, with short treatments (3-6 months) more disadvantaged than >48-month treatments (HR 2.783, CI 95% 1.267-6.114, P=0.008). Concomitant aminosalicylates were the only predictors of sustained remission during AZA therapy (P=0.009). The overall colectomy rate was 10%. Predictors of colectomy were drug-related toxicity as the cause of AZA withdrawal (P=0.041), no post-AZA drug therapy (P=0.031), and treatment duration (P<0.0005). Discontinuation of AZA while UC is in remission is associated with a high relapse rate. Disease extent, lack of sustained remission during AZA, and discontinuation due to toxicity could stratify relapse risk. Concomitant aminosalicylates were advantageous. Prospective randomized controlled trials are needed to confirm whether treatment duration is inversely associated with outcome.

Drug Induced Intracranial Hypertension Associated With Sulphasalazine Treatment

A 25-year-old female patient developed headache and papilledema under sulphasalazine treatment for ulcerative colitis. The patient met the International Headache Society's criteria for idiopathic intracranial hypertension. Sulphasalazine was discontinued and the patient was given azathioprine for ulcerative colitis and acetazolamide for intracranial hypertension. Three weeks later, her examination was normal and lumbar puncture revealed an opening pressure of 180-mm H(2)O. Sulphasalazine is a product of 5 aminosalicylate (5 ASA) and there seems to be a relationship between the administration of sulphasalazine and the onset of intracranial hypertension symptoms. Early diagnosis of intracranial hypertension is important in patients with ulcerative colitis receiving 5 ASA treatment to prevent visual complications.

Merkel Cell Carcinoma Arising after Therapy with Azathioprine for Ulcerative Colitis

Merkel Cell Carcinoma Arising after Therapy with Azathioprine for Ulcerative Colitis

New onset of atrial fibrillation after introduction of azathioprine in ulcerative colitis: case report and review of the literature

We present the case of a 52-year-old man with steroid-dependent ulcerative colitis, needing immunosuppressive therapy with azathioprine. The drug had been started 3 years earlier, but stopped after a few months because the patient reported palpitations, lipothymia, nausea and vomiting. Given the continued steroid-dependent ulcerative colitis and the lack of clinical documentation about a reaction with a dubious relationship to azathioprine, we decided to rechallenge the patient with the drug under clinical monitoring and after informed consent. After starting 50 mg of azathioprine, the patient showed general malaise, nausea and vomiting. An ECG showed atrial fibrillation, and the patient reported that the symptoms were similar to those previously experienced. We have found two other cases of similar onset of atrial fibrillation after azathioprine use, although some confounding elements in these episodes make the possible causal relationship between the drug and this adverse event uncertain.

Rate response to Azathioprine in ulcerative colitis (UC)

Rate response to Azathioprine in ulcerative colitis (UC)

Immunosuppressive therapy for ulcerative colitis: results of a nation‐wide survey among consultant physician members of the British Society of Gastroenterology

The role of immunosuppressive therapy in ulcerative colitis remains controversial. There is little information available on how frequently immunosuppressives are used, the circumstances, dose and duration of use and perceived benefit. A postal survey was sent to consultant gastroenterologist members of the British Society of Gastroenterology. Questionnaires were returned by 81% of the 496 UK consultants approached. Azathioprine use was frequent, with 93% reporting previous use and 86% use within the past year. Although 95% usually prescribed a < or =2 mg/kg dose, only 39% were prepared to prescribe higher doses. There was marked variation in duration of use, with 46% using azathioprine for <2 years and 17% continuing it for 4 years or longer. Consultants with more experience of azathioprine in ulcerative colitis used it at higher maintenance doses for longer periods, and in patients with less extensive disease. Cyclosporin use was reported by 47% of those caring for ulcerative colitis patients, with 36% having used it at least once in the past year. However, 65% of users estimated that fewer than 50% of patients subsequently avoided colectomy. On stopping cyclosporin only 21% always introduced an alternative immunosuppressive, while 23% never did so. Potentially serious side-effects attributable to azathioprine and cyclosporin were reported by 36% and 45% of users of each drug, respectively. This survey reveals considerable variation in the amount and pattern of immunosuppressive use in ulcerative colitis, with serious side-effects commonly seen. There is a pressing need for further randomized controlled trials to provide reliable evidence as to how immunosuppressive therapy should be used in ulcerative colitis.

The role of azathioprine in the management of ulcerative colitis

The use of azathioprine in ulcerative colitis is unclear. The authors present the details and outcome of 47 patients who received azathioprine for either a) severe, resistant disease otherwise requiring surgery (28 patients) or b) patients with steroid dependence who have been followed up for at least 12 months (19 patients). Duration of treatment ranged from one week to 66 months (median, 12 months). Of the patients in Group I, 13 (46 percent) achieved remission, 11 of whom had not relapsed during a median follow-up of 22 months (range, 12 to 58 months), and 15 underwent surgery one week to 12 months (median, five weeks) after commencing azathioprine. In Group II, steroids were withdrawn or reduced in 12 (63 percent) patients and three patients required colectomy. Side effects necessitating withdrawal of azathioprine occurred in 12 patients (hematologic effects, 6 patients; gastrointestinal effects, 4 patients; other effects, 2 patients). Two patients required a reduced dose of azathioprine because of leukopenia. The authors conclude that azathioprine is a valuable therapeutic option in selected patients with ulcerative colitis.

Azathioprine in Ulcerative Colitis: Final Report on Controlled Therapeutic Trial

Eighty patients, all of whom were suffering from a frank clinical attack of ulcerative colitis, were admitted to the trial. The attack was treated with a standard course of corticosteroids and the patients were immediately placed on treatment with either azathioprine in a dose of 2.5 mg/kg body weight or dummy tablets. The trial tablets were continued for one year while the patients were maintained under regular clinical, sigmoidoscopic, histological, haematological, and biochemical surveillance. If a patient relapsed during such maintenance treatment he or she was treated with a further course of corticosteroids without interrupting maintenance treatment.In the treatment of an actual attack of ulcerative colitis the results in the attacks which brought the 80 patients into the trial show that no benefit came from the addition of azathioprine to a standard course of corticosteroid therapy.Patients admitted in their first attack of ulcerative colitis showed no benefit from the one-year maintenance treatment with azathioprine, the benefits of which were confined to patients admitted in a relapse of established disease. Even in these the difference between the treated group and the control group failed to reach statistical significance, but the difference was big enough to suggest that there is a prima facie case for regarding azathioprine as of some benefit in this group of patients.