Incidence of intestinal & extra-intestinal cancers among individuals with Crohn's disease in northern India.

Background & objectives Crohn's disease (CD) is associated with a higher risk of malignancy, which is attributed to disease behaviour and the usage of immunosuppressants. The burden of malignancy in CD is scarcely reported from Asia. We report real-world data on CD-related malignancy from a northern Indian cohort. Methods This retrospective analysis included individuals with CD who were followed up at the All India Institute of Medical Sciences, New Delhi, from 2005 to 2021. The standardized incidence ratio (SIR) was used to calculate the relative risk of malignancy in CD affected individuals compared to the general population. Results In this study, 952 study participants were included, with a mean age at diagnosis of 36.9±15.11 yr; 61.1 per cent were male. The median follow-up duration was 34 months [IQR (interquartile range): 19-73]. Most study participants received steroids (76.7%), immunomodulators (68.7%), or anti-TNF therapy (10.8%). The overall incidence of malignancy was 1.05 per cent, indicating a 10.45 times higher risk in CD [SIR: 10.45; 95% Confidence interval (CI):4.98-17.96]. Eight out of 826, 1 of 106 and 1 of 25 study participants developed malignancy in the first, second and third decades, respectively. The cumulative risk of malignancy was 2.7, 5.5, and 13.4 per cent in the first, second, and third decades, respectively. Regarding bowel malignancies, one study participant each developed ileocaecal adenocarcinoma, anorectal adenocarcinoma, malignant rectal fibrous histiocytoma, and gastric adenocarcinoma. Extraintestinal malignancies included single cases each of follicular neoplasia of the thyroid, neuroendocrine tumour of the pancreatic tail, breast cancer, hepatocellular cancer, oral cancer, and prostate cancer. No cases of lymphoma or skin malignancy were reported. Interpretation & conclusions At 30 yr, the cumulative risk of malignancy among Indian CD-affected individuals was 13.4 per cent, with a SIR of 10.45 (95% CI: 4.98- 17.96). The risk increased with increasing age at disease onset and duration.

Intravenous albumin infusion does not augment the response rate to a combination of exclusive enteral nutrition and intravenous steroids in acute severe ulcerative colitis: a randomized controlled trial.

INTRODUCTION: 30-40% patients with acute severe ulcerative colitis (ASUC) fail intravenous (IV) steroids requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition (EEN) has been shown to improve steroid response and albumin levels. Albumin infusion due to its anti-inflammatory and anti-oxidant properties might further improve steroid response in ASUC, which was evaluated in present study. METHODS: In this open-label randomized controlled trial, patients with ASUC were randomized in 1:1 ratio to albumin + standard of care (SOC) + EEN vs. SOC + EEN (Jan2021 - Feb2023). Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in albumin arm were administered 5 days of 20% w/v intravenous albumin (100 ml). Primary outcome was 1) steroid failure (need for rescue medical therapy or colectomy) and 2) proportion of patients with adverse events. RESULTS: Sixty-one patients (albumin-30, SOC-31)(mean age-31.6±0.4 years, male-57.4%), were included. Baseline characteristics were comparable. There was no difference in steroid failure between albumin and SOC arm(10/30(33.33 %) vs 13/31(41.94 %), p=0.49). No adverse events were reported with albumin infusions. Colectomy rate(10% vs 9.68%, P=1), response to salvage medical therapy (88.89% vs 76.92%, P=0.62) and median duration of hospitalization (10.5(7-16) vs 10(7-20), P=0.43) were also comparable. Long-term composite outcome of colectomy and re-admission rates was numerically higher in the albumin than SOC arm (37.04% vs 17.86%, p>0.05), although it did not reach statistical significance. CONCLUSION: There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn's Disease.

BACKGROUND: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population. METHODS: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model. RESULTS: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time. CONCLUSIONS: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing. TRIAL REGISTRATION: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .

Combined or High Dose Immunosuppression in Inflammatory Bowel Disease patients who are NUDT15 Homozygous Harbors Risk of Developing Invasive Fungal Infections: A Case Series.

NUDT15 homozygous mutations predispose patients to severe leucopenia, which invites risk of disseminated fungal infections when high doses or a combination of immunosuppressives are administered in this patient population.

Coconut Water Induces Clinical Remission in Mild to Moderate Ulcerative Colitis: Double-blind Placebo-controlled Trial.

BACKGROUND & AIMS: Coconut water (CW) is anti-inflammatory, can manipulate the gut microbiome, and is a rich source of potassium. Gut microbiome modulation improves outcomes in ulcerative colitis (UC), and potassium possesses in vitro anti-inflammatory property. We evaluated the effect of CW as an adjunct therapy for patients with mild-moderate UC. METHODS: This single-center, double-blind, placebo-controlled trial randomized patients with mild to moderate (Simple Clinical Colitis Activity Index [SCCAI]: 3-9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity [UCEIS] >1) in 1:1 ratio to CW + standard medical therapy (SMT) vs placebo + SMT. Four hundred mL of CW was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤2), and secondary outcome measures were clinical response (SCCAI decline ≥3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks. RESULTS: Of 121 patients screened, 95 were included for modified intention to treat analysis (CW, n = 49; placebo, n = 46) (mean age, 37.2 ± 11.2 years; males, 54.1%; disease duration, 48 months [interquartile range (IQR), 24-90 months]; pancolitis, 26.1%; SCCAI, 5 [IQR, 4-6]; UCEIS, 4 [IQR, 3-5]). Clinical response (57.1% vs 28.3%; odds ratio [OR], 3.4; 95% confidence interval [CI], 1.4-7.9; P = .01), remission (53.1% vs 28.3%; OR, 2.9; 95% CI, 1.2-6.7; P = .02), and proportion of patients with fecal calprotectin (FCP) <150 µg/g (30.6% vs 6.5%; OR, 6.3; 95% CI, 1.7-23.6; P = .003) were significantly higher in CW. The relative abundance of bacterial taxa that had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP increased at 8 weeks in CW, and this effect was independent of disease activity and dietary fiber. Adverse events were comparable, and no patient developed hyperkalemia. CONCLUSIONS: CW was more effective than placebo for induction of clinical remission in patients with mild to moderate UC. The trial was prospectively registered on Clinical Trials Registry of India (ctri.nic.in, Number: CTRI/2019/03/01827).

Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis.

BACKGROUND AND AIMS: Thiopurines are viable option for the treatment of inflammatory bowel disease [IBD] in resource-limited countries. However, data on the effect of disease duration at thiopurines initiation on long-term effectiveness are limited. METHOD: We performed a propensity matched analysis of a retrospective cohort of patients with ulcerative colitis [UC] and Crohn's disease [CD]. Patients initiated on thiopurines early in the disease course [≤2 years] were compared with those started late [>2 years]. Effectiveness was defined as no requirement for hospitalisation, anti-tumour necrosis factor [TNF] agents, or surgery, and minimum steroid requirement [≤1 steroid course in 2 years] during follow-up. RESULTS: A total of 988 [UC: 720, CD: 268] patients were included (male: 665 [60.8%], median age: 40 [32-51] years, median follow-up: 40 [19-81] months). Overall effectiveness at 5 and 10 years was 79% and 72% in UC, and 69% and 63% in CD, respectively. After propensity score matching, there was no difference in 5- and 10-year effectiveness between early and late thiopurine initiation groups either for UC [81% and 80% vs 82% and 74%; p = 0.92] or CD [76% and 66% vs 72% and 51%, p = 0.32]. Male sex for UC (negative: hazard ratio [HR]: 0.67, 95% confidence interval [CI): 0.45-0.97; p = 0.03), and ileal involvement [positive: HR: 3.03, 95% CI: 1.32-6.71; p = 0.008], steroid-dependent disease [positive: HR: 2.70, 95% CI: 1.26-5.68; p = 0.01] and adverse events [negative: HR: 0.47, 95% CI:0.27-0.80; p = 0.005] for CD were predictors of thiopurine effectiveness. CONCLUSION: Thiopurines have sustained long-term effectiveness in both UC and CD. However, early thiopurine initiation had no better effect on long-term disease outcome compared with late initiation.

"Prevalence, Predictors, and Impact of Hepatic Steatosis in Patients With Ulcerative Colitis: A Prospective Observational Cohort Study".

Background and Aims: There are no prospective studies evaluating effect of non-alcoholic fatty liver disease (NAFLD) in patients with ulcerative colitis (UC). This prospective observational study assessed the prevalence of NAFLD, its predictors, and its effect on long-term outcomes in UC. Methods: Consecutive UC patients underwent transient elastography, body composition analysis, bone densitometry, anthropometry, and baseline demographic and subjective global assessment. NAFLD was diagnosed by controlled attenuation parameter of >260 dB/m. To evaluate predictors and outcomes, patients of UC with NAFLD (n = 29) were compared with age- and sex-matched patients of UC without NAFLD (n = 27). Results: Among 107 patients of UC (mean age-29 ± 10.6 years; males = 56%, median disease duration-48 [interquartile range: 24-84] months, left sided/pancolitis = 84%), 27% (n = 29) had NAFLD. Patients with body mass index (BMI) > 23 kg/m2 had higher proportion of NAFLD than with normal or low BMI (54.7% [23/42] vs 10% [5/50] vs 6.7% [1/15]). Patients with NAFLD had high BMI (P < 0.001), waist circumference, and fat mass (P < 0.001) but similar fat-free mass (P = 0.798) compared to patients without NAFLD. There was no difference in immunosuppressant and cumulative steroid exposure between two groups. Dietary parameters including daily energy, protein, fat, and carbohydrate intake were similar between the two groups. On multivariate analysis, high BMI was found to be predictive and low socioeconomic status as a protective factor of NAFLD. On long-term follow-up of three years, there was no difference in steroid, or biologic requirement, disease-related hospitalization, or composite of all three outcomes between two groups. Conclusion: The prevalence of NAFLD was found in nearly a quarter of patients of UC and was affected by metabolic parameters rather than disease activity.

Low prevalence of Clostridioides difficile infection in acute severe ulcerative colitis: A retrospective cohort study from northern India.

BACKGROUND: The incidence of Clostridioides difficile infection (CDI) is high in ulcerative colitis and is associated with disease flares and adverse outcomes. However, the data on the dynamics of CDI in patients with acute severe ulcerative colitis (ASUC) is rather scarce. We evaluated the prevalence of CDI in patients with ASUC. METHODS: This retrospective analysis of a prospectively maintained cohort admitted to the All India Institute of Medical Sciences, India, from May 2016 to December 2021, included patients with ASUC (as per Truelove and Witts criteria) who were tested for CDI. CDI testing was performed using enzyme-linked immunoassay for toxins A and B. Risk factors for developing CDI were analyzed along with short-term outcomes of ASUC. Steroid failure was defined as the need for medical rescue therapy or colectomy. RESULTS: Total 153 patients with ASUC were included (mean age 34.92 ± 12.24 years; males 56.2%; disease duration 36 (IQR: 16-55.5) months, pancolitis 67.3%). Ninety-eight (63.4%), 72 (47%) and 10 (6.5%) patients, respectively, had received steroids, azathioprine and biologics in the past. Forty patients (26.14%) had a prior history of ASUC. Among risk factors for CDI, 14% of the patients had prior admission within 30 days, 22.2% had a recent history of antibiotics and 3.9% had long-term non-steroidal anti-inflammatory drug intake. Only one sample was positive for Clostridioides difficile toxin assay. Tissue Cytomegalovirus DNA-PCR positivity was noted in 57 patients (37.3%). Fifty-seven patients (37.3%) had steroid failure, 35 required medical rescue therapy and 30 (19.6%) required colectomy (eight after medical rescue therapy failure). CONCLUSION: Despite antecedent risk factors for CDI, the overall prevalence of CDI in ASUC was low and the outcomes were determined by underlying disease severity.

Revised Algorithmic Approach to Differentiate Between Nonspecific and Specific Etiologies of Chronic Terminal Ileitis.

INTRODUCTION: Chronic isolated terminal ileitis (TI) may be seen in Crohn's disease (CD) and intestinal tuberculosis (ITB) in addition to other etiologies that may be managed symptomatically. We developed a revised algorithm to distinguish patients with a specific etiology from a nonspecific etiology. METHODS: Patients with chronic isolated TI followed up from 2007 to 2022 were retrospectively reviewed. A specific (ITB or CD) diagnosis was made based on standardized criteria, and other relevant data were collected. Using this cohort, validation of a previously suggested algorithm was conducted. Furthermore, based on the results of a univariate analysis, a multivariate analysis with bootstrap validation was used to develop a revised algorithm. RESULTS: We included 153 patients (mean age 36.9 ± 14.6 years, males-70%, median duration-1.5 years, range: 0-20 years) with chronic isolated TI of whom 109 (71.2%) received a specific diagnosis (CD-69, ITB-40). On multivariate regression and validation statistics with a combination of clinical, laboratory, radiological, and colonoscopic findings, an optimism corrected c-statistic of 0.975 and 0.958 was obtained with and without histopathological findings, respectively. Revised algorithm, based on these, showed sensitivity, specificity, positive and negative predictive values, and overall accuracy of 98.2% (95% CI: 93.5-99.8), 75.0% (95% CI: 59.7-86.8), 90.7% (95% CI: 85.4-94.2), 94.3% (95% CI: 80.5-98.5) and 91.5%(95% CI:85.9-95.4), respectively. This was more sensitive and specific than the previous algorithm (accuracy 83.9%, sensitivity 95.5%, and specificity 54.6%). DISCUSSION: We developed a revised algorithm and a multimodality approach to stratify patients with chronic isolated TI into specific and nonspecific etiologies with an excellent diagnostic accuracy, which could potentially avoid missed diagnosis and unnecessary side effects of treatment.

Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring.

BACKGROUND/AIMS: Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Inflammatory bowel disease patients treated with anti-TNF agents (January 2005-October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. RESULTS: One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28-100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03-0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15-0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03-0.39; P=0.001) on multivariate analysis respectively. CONCLUSIONS: Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.

Recanalized Paraumbilical Vein Leading to Hepatic Myelopathy Causing Spastic Paraparesis in a Patient with Chronic Liver Disease.

A 34-year-old male visited our hospital with complaints of recurrent episodes of altered behavior since past 6 months along with difficulty in walking since past 3 months. He was diagnosed of chronic liver disease in the past. Examination revealed spasticity and brisk deep tendon reflexes in both the lower limbs. His blood investigations and spinal cord imaging was normal. Based on his clinical features, a possibility of portosystemic shunting leading to portosystemic encephalopathy (PSE) and shunt myelopathy was suspected. A computed tomography portography showed a recanalized paraumblical vein draining portal blood into external iliac veins. Patient underwent shunt occlusion (Figure- 2). One month after the procedure, while there was no recurrence of symptoms of PSE, those of myelopathy remained unchanged. Shunt myelopathy is a rare complication of spontaneous or iatrogenic portosystemic shunts. Unlike PSE, the management of shunt myelopathy is uncertain due to limited evidence. Limited evidence suggests reversal of myelopathy after early shunt occlusion, highlighting the irreversible changes that may set in spinal cord due to delayed diagnosis. Our case highlights an important but a rare complication of portosystemic shunting in chronic liver disease which should be kept in mind if these patients develop symptoms attributable to spinal cord disease.

High seroprevalence against SARS-CoV-2 in non-vaccinated patients with inflammatory bowel disease from Northern India.

BACKGROUND: The information on seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients with inflammatory bowel disease (IBD) and its comparison to healthy controls is sparse. We compared the seroprevalence rates in patients with IBD and healthy controls (HCs). METHODS: Patients with IBD and HCs (contact of patients) underwent SARS-CoV-2 antibody testing (chemiluminescent immunoassay: Siemens kit IgG against antigen-S1RBD) between July 2020 and April 2021. Information on demography, disease characteristics, drug history and past history of SARS-CoV-2 infection were noted. Patients on 5-aminosalicylic acid or no treatment were considered not on immunosuppressants and those who had received steroids, thiopurines or methotrexate within six months of inclusion were considered being on immunosuppressants. RESULTS: A total of 235 patients (51.9%, males; mean age, 38.7 ± 12.4 years; median disease duration, 60 months [interquartile range, IQR: 36-120]) (ulcerative colitis [UC]: 69.4%, Crohn's disease [CD]: 28.9%, IBD unclassified [IBDU]: 1.7%) and 73 HCs (mean age, 39.6 ± 10.9 years, 80% males) were enrolled. Of the 235 patients, 128 (54.5%) patients were on immunosuppressants and 107 (45.5%) were not on immunosuppressants. Seventy-four (31.5%) patients were seropositive, of which two (0.9%) had previous history of SARS-CoV-2 infection and none received coronavirus disease-19 (COVID-19) vaccine. Seroprevalence between IBD patients and HCs (32% vs. 27%, p > 0.05) and between patients with and without immunosuppressants (28.1% vs. 36%, p > 0.05) was similar. Age, gender, disease type, duration and activity in the last six months; and medication use were similar between patients with positive and negative serology. There was a progressive increase in seroprevalence from July 2020 to April 2021. CONCLUSION: Up to 1/3rd of patients with IBD were seropositive for immunoglobulin G (IgG) SARS-Cov-2 antibody indicating high seroprevalence in patients with IBD from Northern India.

Efficacy and safety of biosimilar versus originator infliximab in patients with inflammatory bowel disease: A real-world cohort analysis.

BACKGROUND: Anti-tumor necrosis factor (anti-TNF) monoclonal antibody, infliximab, is the primary therapeutic modality for patients with Crohn's disease (CD) and ulcerative colitis (UC), refractory to conventional therapy. Biosimilars of infliximab have been shown to have equivalent efficacy to originator infliximab. We compared the safety and efficacy of infliximab biosimilar with the originator in Indian patients with inflammatory bowel disease (IBD). METHODS: Patients with IBD treated with either originator or biosimilar infliximab from January 2005 to October 2020 were included in this retrospective analysis. The safety and efficacy of originator or biosimilar infliximab in inducing and maintaining clinical remission at weeks 14 and 52 for CD and UC were evaluated. Disease activity was estimated at baseline, after induction therapy, after 1 year of treatment, and during 12 months of follow-up. RESULTS: In all, 137 patients (82 CD; 55 UC) were included, of whom 102 were on originator, and 35 patients received biosimilar. In biosimilar group, clinical response and remission rates at weeks 14 and 52 were 84.2%, 58% and 68.4%, 52.6% in CD and 81.2%, 56.2% and 68.7%, 62.5% in UC patients, respectively. Among patients who were on originator, clinical response and remission rates at weeks 14 and 52 were 79.4%, 46% and 57.1%, 43% in CD and 72%, 64.1% and 66.7%, 56.4% in UC patients, respectively. Thirty-three (24.1%) patients experienced adverse events; eighteen developed tuberculosis (TB), of whom 17 received originator and one patient received biosimilar. CONCLUSIONS: Infliximab biosimilar is comparable to originator infliximab in terms of safety profile and its efficacy in inducing and maintaining remission in patients with IBD.

Relapse rates after withdrawal of thiopurines in patients with inflammatory bowel disease.

PURPOSE: Withdrawal of thiopurines after remission is associated with an increased risk of relapse in patients with inflammatory bowel disease (IBD). However, long-term data on thiopurine withdrawal is limited, especially from developing countries where the cost of long-term therapy poses a significant burden on patients. METHODS: Patients with IBD on thiopurine monotherapy for ≥ 4 months, who stopped thiopurines while in clinical remission and were not on any other immunomodulator or biologics at the time of withdrawal, were included in this retrospective analysis. RESULTS: Among 1093 patients with IBD on thiopurine monotherapy, 461 patients stopped thiopurine due to various reasons. Among these, 218 (ulcerative colitis (UC) = 179; Crohn's disease (CD) = 39) patients were in clinical remission and were continued on mesalamine. Overall, 36.7% (n = 80) relapsed after a median duration of 20 months (IQR: 9-49). Relapse rate was higher in UC than CD (39.7% vs 23%, p = 0.055). Cumulative probabilities of relapse were 17%, 34%, and 44% at the end of 1, 3, and 5 years, respectively. The relapse rate at 5 years was significantly lower in patients who had stopped azathioprine after 4 years of therapy (31% vs 54%, p = 0.007). On multi-variate cox regression analysis, male sex [HR: 1.6(1.0-2.6), p = 0.02] and short duration of therapy with thiopurines [HR: 1.02 (1.01-1.02), p = 0.004] before withdrawal were associated with increased risk of relapse. CONCLUSION: Approximately 50% patients with IBD in remission would relapse after 5 years of thiopurine withdrawal. Male sex and shorter treatment duration predict relapse. Treatment should be continued in patients who tolerate and maintain remission on long-term thiopurine.

Minimal risk of lymphoma and non-melanoma skin cancer despite long-term use of thiopurines in patients with inflammatory bowel disease: A longitudinal cohort analysis from northern India.

BACKGROUND AND AIM: Thiopurines are widely used to maintain remission in both ulcerative colitis (UC) and Crohn's disease (CD). Reported effectiveness and tolerability rates have been variable across studies. There are only sparse data in Asian population regarding the long-term efficacy and safety of thiopurines. METHODS: Records of 5351 patients followed up at inflammatory bowel disease (IBD) clinic, All India Institute of Medical Sciences, New Delhi from 2004 to 2020 were evaluated retrospectively. Safety was evaluated in terms of long-term adverse events and development of malignancy. RESULTS: Of 5351 patients with IBD, 1093 who received thiopurine for > 3 months (UC = 788 [proctitis-1.9%, left-sided colitis-44.9%, & pancolitis-53.1%] & CD = 305 [inflammatory-42.6%, stricturing-46.9%, & fistulizing-10.5%]) were included (60.8%-male patients). Follow up and treatment duration on thiopurine were 7 (4-12) years and 39.4 ± 40.3 months, respectively, with 254 (23.2%) patients receiving thiopurines for more than 5 and 68 (6.2%) receiving for more than 10 years. Three hundred and fifty-nine (UC: 249 [31.6%]; CD: 110 [36.1%]; P = 0.1) patients developed adverse events; commonest was myelosuppression (23.4%) followed by gastrointestinal intolerance (3%), flu-like illness (1.7%), and arthralgia/myalgia (1.4%). Myelosuppression was the commonest cause of thiopurine withdrawal. No patient (including 254 patients on thiopurine for ≥ 5 years) developed lymphoma or non-melanoma skin cancer. The cumulative probability of staying free from adverse events in overall IBD cohort at 1, 2, and 5 years was 78.6%, 71.9%, and 68.4%, respectively, and this was comparable between UC and CD (P = 0.09). CONCLUSION: Long-term follow up of patients with IBD from northern India on thiopurine monotherapy demonstrated minimal risk of development of lymphoma as well as non-melanoma skin cancer.

Stringent screening strategy significantly reduces reactivation rates of tuberculosis in patients with inflammatory bowel disease on anti-TNF therapy in tuberculosis endemic region.

BACKGROUND: Anti-tumor necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to an increased risk of tuberculosis (TB) reactivation despite latent tuberculosis (LTB) screening, especially in TB endemic regions. AIM: We evaluated the effect of stringent screening strategy and LTB prophylaxis on TB reactivation. METHODS: We performed an ambispective comparison between patients who received anti-TNF therapy after January 2019 (late cohort) and between Jan 2005 and Jan 2019 (early cohort). Late cohort patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, chest X-ray, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy. RESULTS: One hundred seventy-one patients (63: ulcerative colitis/108: Crohn's disease, mean age diagnosis: 28.5 ± 13.4 years, 60% males, median follow-up duration after anti-TNF: 33 months [interquartile range: 23-57 months]) were included. Among the 112 in the early cohort, 29 (26%) underwent complete TB screening, 22 (19.6%) had LTB, 10 (9%) received chemoprophylaxis, and 19 (17%) developed TB. In comparison, in the late cohort, 100% of patients underwent complete TB screening, 26 (44%) had LTB, 23 (39%) received chemoprophylaxis, and only 1(1.7%) developed TB (p < 0.01). On survival analysis, patients in early cohort had a higher probability of TB reactivation compared with the late cohort (HR: 14.52 (95% CI: 1.90-110.61 [p = 0.01]) after adjusting for gender, age at anti-TNF initiation, concomitant immunosuppression, anti-TNF doses, and therapy escalation. CONCLUSION: The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.