Pharmacokinetics and toxicity considerations for antibody-drug conjugates: an overview.

Antibody-drug conjugates (ADCs) is one of the fastest-growing drug-delivery systems. It involves a monoclonal antibody conjugated with payload via a ligand that directly targets the expressive protein of diseased cell. Hence, it reduces systemic exposure and provides site-specific delivery along with reduced toxicity. Because of this advantage, researchers have gained interest in this novel system. ADCs have displayed great promise in drug delivery and biomedical applications. However, a lack of understanding exists on their mechanisms of biodistribution, metabolism and side effects. To gain a better understanding of the therapeutics, careful consideration of the pharmacokinetics and toxicity needs to be undertaken. In this review, different pharmacokinetics parameters including distribution, bioanalysis and heterogeneity are discussed for developing novel therapeutics.

Recent Advances in Targeted Nanocarriers for the Management of Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a life-threatening form of breast cancer which has been found to account for 15% of all the subtypes of breast cancer. Currently available treatments are significantly less effective in TNBC management because of several factors such as poor bioavailability, low specificity, multidrug resistance, poor cellular uptake, and unwanted side effects being the major ones. As a rapidly growing field, nano-therapeutics offers promising alternatives for breast cancer treatment. This platform provides a suitable pathway for crossing biological barriers and allowing sustained systemic circulation time and an improved pharmacokinetic profile of the drug. Apart from this, it also provides an optimized target-specific drug delivery system and improves drug accumulation in tumor cells. This review provides insights into the molecular mechanisms associated with the pathogenesis of TNBC, along with summarizing the conventional therapy and recent advances of different nano-carriers for the management of TNBC.

New observations of the endangered giant freshwater whipray, Urogymnus polylepis, provide further evidence for its distribution and breeding in the north-east coast of India.

The present study reports observations of 13 giant freshwater whipray (Urogymnus polylepis) from commercial fish landings along the north-east coast of India and updates existing records based on field observations and local social media reports. The disc width of the landed specimens ranged from 120 to 223 cm and they weighed 95-300 kg. All 13 specimens observed were mature (nine females and four males) and three females were pregnant, with embryo numbers ranging between 4 and 15. Globally, U. polylepis is listed as 'Endangered', and greater protection measures are needed in India to assist in reversing current population declines.

Transposons: Unexpected players in cancer.

Transposons are repetitive DNA sequences encompassing about half of the human genome. They play a vital role in genome stability maintenance and contribute to genomic diversity and evolution. Their activity is regulated by various mechanisms considering the deleterious effects of these mobile elements. Various genetic risk factors and environmental stress conditions affect the regulatory pathways causing alteration of transposon expression. Our knowledge of the biological role of transposons is limited especially in various types of cancers. Retrotransposons of different types (LTR-retrotransposons, LINEs and SINEs) regulate a plethora of genes that have a role in cell reprogramming, tumor suppression, cell cycle, apoptosis, cell adhesion and migration, and DNA repair. The regulatory mechanisms of transposons, their deregulation and different mechanisms underlying transposon-mediated carcinogenesis in humans focusing on the three most prevalent types, lung, breast and colorectal cancers, were reviewed. The modes of regulation employed include alternative splicing, deletion, insertion, duplication in genes and promoters resulting in upregulation, downregulation or silencing of genes.

Surface engineered nanocarriers for the management of breast cancer.

Breast cancer is commonly known life-threatening malignancy in women after lung cancer. The standard of care (SOC) treatment for breast cancer primarily includes surgery, radiotherapy, hormonal therapy, and chemotherapy. However, the effectiveness of conventional chemotherapy is restricted by several limitations such as poor targeting, drug resistance, poor drug delivery, and high toxicity. Nanoparticulate drug delivery systems have gained a lot of interest in the scientific community because of its unique features and promising potential in breast cancer diagnosis and treatment. The unique physicochemical and biological properties of the nanoparticulate drug delivery systems promotes the drug accumulation, Pharmacokinetic profile towards the tumor site and thereby, reduces the cytotoxicity towards healthy cells. In addition, to improve tumor-specific drug delivery, researchers have focused on surface engineered nanocarrier system with targeting molecules/ligands that are specific to overexpressed receptors present on cancer cells. In this review, we have summarized the different biological ligands and surface-engineered nanoparticles, enlightening the physicochemical characteristics, toxic effects, and regulatory considerations of nanoparticles involved in treatment of breast cancer.

Emerging innovations in nano-enabled therapy against age-related macular degeneration: A paradigm shift.

Age-related macular degeneration (AMD), a degenerative eye disease, is the major cause of irreversible loss of vision among individuals aged 50 and older. Both genetic and environmental factors are responsible for the progressive damage to central vision. It is a multifactorial retinal disease with features such as drusen, hypopigmentation and/or hyperpigmentation of the retinal pigment epithelium, and even choroidal neovascularization in certain patients. AMD is of two major forms: exudative (wet) and atrophic (dry) with changes affecting the macula leading to impaired vision. Although the retina remains an accessible portion for delivering drugs, there are no current options to cure or treat AMD. The existing expensive therapeutics are unable to treat the underlying pathology but display several side effects. However, recent innovations in nanotherapeutics provide an optimal alternative of drug delivery to treat the neovascular condition. These new-age technologies in the nanometer scale would enhance bioactivity and improve the bioavailability of drugs at the site of action to treat AMD. The nanomedicine also provides sustained release of the drug with prolonged retention after penetrating across the ocular tissues. In this review, the insights into the cellular and molecular mechanisms associated with the pathophysiology of AMD are provided. It also serves to review the current progress in nanoparticle-based drug delivery systems that offer feasible treatments in AMD.

Bioanalytical methodologies for clinical investigation of endocrine-disrupting chemicals: a comprehensive update.

Endocrine-disrupting chemicals (EDCs) are xenobiotics that disrupt the endocrine system in humans at ecologically significant concentrations. Various substances are exposed to human health via routes including food, water, air and skin that result in disastrous maladies at low doses as well. Therefore EDCs need a meticulous strategy of analysis for dependable and consistent monitoring in humans. The management and risk assessment necessitate advancements in the detection methodologies of EDCs. Hyphenated MS-based chromatograph and other validated laboratory analysis methods are widely available and employed. Besides, in vitro bioassay techniques and biosensors are also used to conduct accurate toxicological tests. This article provides a revision of various bioanalytical detection methods and technologies for the clinical estimation of EDCs.

Fluorescence-based method for sensitive and rapid estimation of chlorin e6 in stealth liposomes for photodynamic therapy against cancer.

Chlorin e6 is a chlorine-based porphyrin containing photosensitizer mainly used for the therapy in cancers like neck and head, early-stage lung cancer, and topical skin cancers. The present study provides a comprehensive account of a highly sensitive, precise, and validated method for the quantification of chlorin e6 in its liposomal formulation. This method is based on the systemic study of the fluorescence action of chlorin e6 in acetonitrile solvent. This experiment follows the analytical method validation parameters as per the International Conference on Harmonization (ICH). Chlorin e6 molecule exhibits strong fluorescence at a wavelength of emission 665 nm, upon excitation at a wavelength of excitation 400 nm in acetonitrile. The linearity of the fluorescence concentration plot was observed over a concentration range of 50 to 1000 ng/mL. The developed and validated method was successfully applied for the estimation of encapsulation efficiency in in-house developed stealth liposomes. Also, stock solution stability and photodegradation study of chlorin e6 were further conducted.

Recent advances in targeted nanomedicine as promising antitumor therapeutics.

A tumor serves as a major avenue in drug development owing to its complexity. Conventional therapies against tumors possess limitations such as suboptimal therapeutic efficacy and extreme side effects. These display poor pharmacokinetics and lack specific targeting, with non-specific distribution resulting in systemic toxicity. Therefore, nanocarriers targeted against cancers are increasingly being explored. Nanomedicine aids in maintaining a balance between efficacy and toxicity by specifically accumulating in tumors. Nanotherapeutics possess advantages such as increased solubility of chemotherapeutics, encapsulation of multiple drugs and improved biodistribution, and can ensure tumor-directed drug delivery and release via the approaches of passive targeting and active targeting. This review aims to offer a general overview of the current advances in tumor-targeting nanocarriers for clinical and diagnostic use.

Liquid chromatography-tandem mass spectrometry based method development and validation of S016-1271 (LR8P), a novel cationic antimicrobial peptide for its application to pharmacokinetic studies.

S016-1271 (LR8P) is a broad spectrum novel cationic antimicrobial peptide. The objective of the present study was to develop a selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) based bioanalytical method of S016-1271 peptide in mice and human plasma in order to uncover its pharmacokinetic aspects. The chromatographic separation of S016-1271 (FR8P as internal standard) was achieved on a Waters™ X select CSH-C18 column (75 × 3.0 mm, 2.5 µ) using mixture of acetonitrile and triple distilled water (TDW) both containing 0.05% formic acid as mobile phase. A seven minute linear gradient method was designed to separate analytes from ion suppression at a flow rate of 0.3 mL/min. The extraction of analytes from mice and human plasma was performed through solid phase extraction technique using mixed mode weak cation exchange cartridge (Thermo SOLA WCX 10 mg 1CC) with an extraction recovery of analytes about 75%. Mass spectrometric detection of S016-1271 and FR8P was performed with optimized multiple reaction monitoring (MRM) transitions (Q1/Q3) at 658.8 [M+3H] 3+/653.2 [M+3H-NH3] 3+ and 443.4 [M+5H]5+ /434.7 [y12-NH3]4+,respectively in positive electrospray ionization (ESI) mode. The linearity in mice and human plasma was established over a concentration range of 7.81-250 ng/mL with regression coefficient (r2 > 0.99). The currently developed method was validated as per US-FDA guidelines and found to be within the acceptable limits. The method was successfully applied to intravenous (IV) pharmacokinetic study in mice wherein the levels were detected upto 24 h. The peptide demonstrated poor distribution characteristics which were demonstrated through volume of distribution at steady state (202.71 ± 47.02 mL/kg less than total body water of mice; 580 mL/kg). The clearance of the peptide predominantly occurred through central compartment (central clearance is 25 fold greater than peripheral clearance). Also, the in vitro pharmacokinetic studies demonstrated the stability of S016-1271 in plasma and high plasma protein binding in mice and humans.

Pharmacokinetics, metabolism, bioavailability, tissue distribution and excretion studies of 16α-hydroxycleroda-3, 13(14) Z -dien-15, 16-olide-a novel HMG-CoA reductase inhibitor.

The present study was designed to investigate the oral bioavailability, metabolism, tissue disposition and excretion of 16α-hydroxycleroda-3, 13(14) Z -dien-15, 16-olide (4655K-09), a novel HMG-CoA reductase inhibitor in male Sprague Dawley (SD) rats. Tissue distribution, oral bioavailability and excretion studies of 4655K-09 were carried out in male SD rats through oral administration at active dose of 25 mg/kg. In vitro metabolism studies were carried out in different rat tissues S9 fractions to evaluate primary organs responsible for conversion of parent 4655K-09 to its major active metabolite K-9T. The quantification of both parent and metabolite in different biological matrices was performed using LC-MS/MS method. The oral bioavailability of 4655K-09 was found to be 30% in male SD rats. The biodistribution study was illustrated in terms of tissue to plasma area under curve (AUC)0-∞ ratio (Kp) revealed the preferential distribution of 4655K-09 and K-9T to target site, i.e. liver. In vitro tissue S9 fraction stability assay demonstrated the rapid and extensive metabolic conversion of 4655K-09 to K-9T, primarily through liver and kidney. Very low amount of parent and metabolite were excreted unchanged in urine and faeces. The present studies established 4655K-09 bioavailability, tissue disposition, excretion and tissue-specific metabolic conversion to K-9T which could assist in its further development as antihyperlipidemic drug.

Spatio-temporal variability of physico-chemical variables, chlorophyll a, and primary productivity in the northern Arabian Sea along India coast.

The present study attempts to understand the seasonal and spatial variations in the physico-chemical (temperature, pH, salinity, dissolved oxygen, and nutrients) and productivity characteristics of the northern Arabian Sea off the Indian coast. Samples were collected from four different sites off the Veraval coast. The values of the physical and chemical variables were higher during the summer season, whereas nutrient concentrations were high during the winter season due to the maturity of intake nutrients during post-monsoon and winter convective mixing during the northeast monsoon. The dissolved oxygen (DO) concentration was strongly and positively correlated with the net primary productivity (NPP) and chlorophyll a (Chl-a) content to support productivity along the region. Dissimilarity in study variables was observed between the inshore and offshore locations. Principal component analysis revealed a strong relationship between nutrients and productivity variables (Chl-a and NPP). Nutrient levels were high at inshore sites, which can be attributed to the heavy nutrient load from land-based anthropogenic activities and impact due to natural processes like water mixing, sedimentation, and wave activities. Nutrients were strongly and positively correlated with the productivity variables, i.e., Chl-a and NPP. Chl-a positively correlated with NPP (r = 0.90), which indicates that it is a principle productivity pigment in the marine ecosystem.

Long-term follow-up reveals high incidence of colorectal cancer in Indian patients with inflammatory bowel disease.

BACKGROUND: As the magnitude of sporadic colorectal cancer (CRC) in India is low, magnitude of CRC in ulcerative colitis (UC) is also considered low. As a result, screening for CRC in UC although advocated may not be followed everywhere. We report our data of UC-related CRC from a low-incidence area of sporadic CRC. METHODS: A total of 1012 patients with left-sided colitis/pancolitis having more than one full-length colonoscopy performed at least a year after the onset of symptoms were included in retrospective analysis of prospectively maintained case records. In addition, 136 patients with duration of disease >10 years underwent surveillance white-light colonoscopy prospectively during the study period. RESULTS: A total of 1012 individuals were finally included (6542 person-years of follow-up, 68.5% males, disease duration: 6.4 ± 6.8 years). Twenty (1.97%) patients developed CRC. Two (10%) patients developed CRC during the first decade, 10/20 (50%) during the second and 8/20 (40%) after the second decade of disease. The cumulative risk of developing CRC was 1.5%, 7.2% and 23.6% in the first, second and third decade, respectively. Of 136 high-risk UC cases, five (3.6%) had CRC on screening colonoscopy. Disease duration and increasing age of onset were associated with higher risk of CRC. CONCLUSIONS: Cumulative risk of CRC in Indian UC patients is as high as 23.6% at 30 years. The risk of CRC increases with increasing age of onset and increasing duration of disease. A low risk of sporadic CRC does not confer a low risk of UC-related CRC, and regular screening is warranted.

Development and validation of visceral fat quantification as a surrogate marker for differentiation of Crohn's disease and intestinal tuberculosis.

BACKGROUND AND AIM: Crohn's disease (CD) and intestinal tuberculosis (ITB) have close phenotypic resemblance. Mesenteric fat (a component of visceral fat [VF]) hypertrophy and fat wrapping, which is visible radiologically as fibrofatty proliferation, is seen more commonly in CD than in ITB. AIM: The present study was conducted to study the role of VF in differentiating CD and ITB. METHODS: Visceral fat area and subcutaneous (SC) fat area were measured on computed tomography in two cohorts (development and validation). VF/SC ratio was also calculated for all patients. In the development cohort, retrospective data collection was carried out for 75 patients with CD and ITB who were on follow-up from January 2012 to November 2014. In the validation cohort, 82 patients were recruited prospectively from December 2014 to December 2015 and were diagnosed as CD or ITB according to standard diagnostic criteria. RESULTS: Visceral fat area and VF/SC ratio were significantly higher in CD patients (n = 42: development, n = 46: validation) than in ITB patients (n = 33: development, n = 36: validation) in both the development (106.2 ± 63.5 vs 37.3 ± 22, P = <0.001; 1.1 ± 0.57 vs 0.43 ± 0.24, P = <0.001) and validation cohorts (102.2 ± 69.8 vs 55.8 ± 44.9, P = 0.01; 1.2 ± 0.68 vs 0.56 ± 0.33, P = <0.001). A cut-off of 0.63 for VF/SC ratio in the development cohort had a high sensitivity (82%) and specificity (81%) in differentiating CD and ITB. Similar sensitivity (81%) and specificity (78%) were seen when this cut-off was applied in the validation cohort. CONCLUSION: The VF/SC ratio is a simple, cost-effective, non-invasive and single objective parameter with a good sensitivity and specificity to differentiate CD and ITB.

Perfusion CT - Can it resolve the pancreatic carcinoma versus mass forming chronic pancreatitis conundrum?

OBJECTIVES: To evaluate the utility of perfusion CT (PCT) in differentiating pancreatic adenocarcinoma from mass forming chronic pancreatitis (MFCP). METHODS: In this ethically approved study, PCT was performed in 122 patients with pancreatic masses of which 42 patients had pancreatic adenocarcinoma and 13 had MFCP on histopathology. Perfusion parameters studied included blood flow (BF), blood volume (BV), permeability surface area product (PS), time to peak (TTP), peak enhancement intensity (PEI) and mean transit time (MTT). Twenty five controls with no pancreatic pathology were also studied. RESULTS: Amongst the perfusion parameters BF and BV were found to be the most reliable for differentiating between adenocarcinoma and mass forming pancreatitis. Although they were reduced in both pancreatic adenocarcinoma (BF- 16.6 ± 13.1 ml/100 ml/min and BV- 5 ± 3.5 ml/100 ml) and MFCP (BF- 30.4 ± 8.7 ml/100 ml/min and BV- 8.9 ± 3.1 ml/100 ml) as compared to normal controls (BF- 94.1 ± 24 ml/100 ml/min and BV- 36 ± 10.7 ml/100 ml) but the extent of reduction was greater in pancreatic adenocarcinoma than in MFCP. Based on ROC analysis cut off values of 19.1 ml/100 ml/min for BF and 5 ml/100 ml for BV yielded optimal sensitivity and specificity for differentiating pancreatic adenocarcinoma from MFCP. CONCLUSIONS: PCT may serve as an additional paradigm for differentiating pancreatic adenocarcinoma from mass forming chronic pancreatitis and a useful tool for detecting masses which are isodense on conventional CT.

Role of random biopsies in surveillance of dysplasia in ulcerative colitis patients with high risk of colorectal cancer.

BACKGROUND/AIMS: Recent data suggest that the incidence of ulcerative colitis (UC) related colorectal cancer (CRC) in India is similar to that of West. The optimum method for surveillance is still a debate. Surveillance with random biopsies has been the standard of care, but is a tedious process. We therefore undertook this study to assess the yield of random biopsy in dysplasia surveillance. METHODS: Between March 2014 and July 2015, patients of UC attending the Inflammatory Bowel Disease clinic at the All India Institute of Medical Sciences with high risk factors for CRC like duration of disease >15 years and pancolitis, family history of CRC, primary sclerosing cholangitis underwent surveillance colonoscopy for dysplasia. Four quadrant random biopsies at 10 cm intervals were taken (33 biopsies). Two pathologists examined specimens for dysplasia, and the yield of dysplasia was calculated. RESULTS: Twenty-eight patients were included. Twenty-six of these had pancolitis with a duration of disease greater than 15 years, and two patients had associated primary sclerosing cholangis. No patient had a family history of CRC. The mean age at onset of disease was 28.89±8.73 years and the duration of disease was 19.00±8.78 years. Eighteen patients (64.28%) were males. A total of 924 biopsies were taken. None of the biopsies revealed any evidence of dysplasia, and 7/924 (0.7%) were indefinite for dysplasia. CONCLUSIONS: Random biopsy for surveillance in longstanding extensive colitis has a low yield for dysplasia and does not suffice for screening. Newer techniques such as chromoendoscopy-guided biopsies need greater adoption.

Frequency, natural course and clinical significance of symptomatic terminal ileitis.

OBJECTIVE: Treatment guidelines for managing symptomatic terminal ileitis (TI) are lacking. We followed up a cohort of symptomatic TI patients to conduct an algorithm for their management. METHODS: Consecutive patients with symptomatic TI from July 2007 to October 2013 were included. Symptomatic TI was defined as isolated terminal ileum ulceration (superficial or deep) and/or nodularity with abdominal symptoms. Patients were diagnosed either with intestinal tuberculosis (ITB) or Crohn's disease (CD) using standard criteria or received only symptomatic treatment according to their clinical manifestations, endoscopic, imaging and histological (specific to ITB/CD vs non-specific) features. Based upon above findings, an algorithm was conducted to differentiate non-specific TI from those with specific etiology (ITB/CD). RESULTS: In all, 63/898 (7.0%) patients with ulcero-constrictive intestinal disease had TI, of which 45 (26 males and 19 females) were included. Fever, diarrhea, weight loss, deep ulcers, and ileal thickening were more frequently observed in patients with ITB or CD having specific treatments compared with those receiving symptomatic treatments. All patients with deep ulcers and those with superficial ulcer and specific histology had ITB/CD. In patients with superficial ulcers and/or nodularity and non-specific inflammation (n = 31), the absence of fever, diarrhea, GI bleeding or weight loss had a negative predictive value of 92% in excluding ITB/CD. CONCLUSIONS: In symptomatic TI patients with superficial ulcers and a non-specific histology, the absence of fever, diarrhea, GI bleeding or weight loss rules out the possibility of significant diagnoses like ITB/CD.

Serum human trefoil factor 3 is a biomarker for mucosal healing in ulcerative colitis patients with minimal disease activity.

BACKGROUND: The goals of treating ulcerative colitis (UC) have shifted from clinical remission to mucosal healing. Non-invasive biomarkers are required to assess mucosal healing as endoscopic assessment is inconvenient for patients. Enhanced expression of trefoil factor 3 (TFF3, a mucin-associated peptide) is observed after injury of the gastrointestinal tract. The present study was designed to evaluate TFF3 as a biomarker of mucosal healing in patients with UC. METHODS: This cross-sectional study included consecutive patients with UC (18-65 years old, disease duration >3 months, either left-sided colitis or pancolitis) who had a Simple Clinical Colitis Activity Index (SCCAI) <6. Colonoscopy was done to assess the presence or absence of mucosal healing (defined using the Baron score) in all patients. Serum level of TFF3 was assessed in all patients and 20 healthy controls. RESULTS: Seventy-four patients were included [mean age 37.2±10.9 years, 47 males, median disease duration 4.8 years (IQR 3-8.3), median SCCAI = 0] in the study. Forty-three patients had mucosal healing (Baron score 0 or 1) and 31 did not (Baron score 2 or 3). Median TFF3 level in patients without mucosal healing was significantly higher than that in patients with mucosal healing [1.5 (IQR 1.2-1.9) vs 1.1 (IQR 0.8-1.3) ng/ml, p = 0.01] and healthy controls [0.85 (IQR 0.7-1.2) ng/ml, p < 0.001]. A serum TFF3 level of <1.27 ng/ml (as determined by the receiver operating characteristic curve; area under the curve 0.73) had sensitivity, specificity, positive predictive value and negative predictive value of 70, 68, 75 and 62%, respectively, for identifying patients with mucosal healing. CONCLUSION: Serum TFF3 can potentially be used as a biomarker to assess mucosal healing in UC patients.

Extraintestinal manifestations of inflammatory bowel disease and intestinal tuberculosis: Frequency and relation with disease phenotype.

BACKGROUND: Extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD), as well as intestinal tuberculosis (ITB) from Asia, are underreported. We, therefore, describe the prevalence of EIMs in Indian IBD and ITB patients and study their relationship with disease extent and severity in IBD. METHODS: This retrospective single-center study included all IBD and ITB patients evaluated from January 2005 to July 2012. Disease profile and frequencies of arthropathies (peripheral and central) and ocular (episcleritis, iritis/uveitis), oral (aphthous stomatitis), skin (erythema nodosum, pyoderma gangrenosum, psoriasis), hepatobiliary (primary sclerosing cholangitis), and thromboembolic manifestations were analyzed. RESULTS: Of 1,652 patients (1146 UC, 303 CD, 203 ITB), frequency of any EIM was 33.2 %, 38.3 %, and 14.3 % in UC, CD, and ITB patients, respectively. Thromboembolism was more common among UC patients with pancolitis than proctitis (p < 0.001) and left-sided colitis (p = 0.02). Primary sclerosing cholangitis was seen in 0.4 % UC patients. Steroid-dependent UC patients had higher frequency of any EIM, peripheral arthropathy, or thromboembolism than patients with no or infrequent steroid requirement (p < 0.05). Peripheral arthropathy (p = 0.02), erythema nodosum (p = 0.01), and aphthous stomatitis (p = 0.004) were more common with CD than with UC patients. Patients with colonic CD had higher frequency of peripheral arthropathy, any EIM, and multiple EIMs than ileal or ileocolonic disease (p < 0.05). Relative to ITB, CD patients had higher frequencies of peripheral arthropathy (p < 0.001), aphthous stomatitis (p = 0.01), any EIM (p < 0.001), and multiple EIMs (p < 0.001). CONCLUSIONS: In Indian IBD and ITB patients, EIMs appear to be related to disease severity in UC and disease location in CD and are significantly more common in CD than in ITB. Overall prevalence of EIMs in these patients is similar to that of the West.