Efficacy and safety of the adalimumab biosimilar Exemptia as induction therapy in moderate-to-severe ulcerative colitis

Vandana Midha,Ramit Mahajan,Varun Mehta,Vikram Narang,Arshdeep Singh,Kirandeep Kaur,Ajit Sood 대한장연구학회 2018 Intestinal Research Vol.16 No.1

Background/Aims: Data on the efficacy and safety of the adalimumab biosimilar Exemptia are limited. Methods: Patients with moderate-to-severe active steroid-refractory ulcerative colitis (UC) treated at Dayanand Medical College and Hospital,India were offered cyclosporine A, biologicals or biosimilars, or surgery. A retrospective analysis was conducted on patients who were treated with the adalimumab biosimilar, Exemptia. These patients were administered an induction dosing scheduleof 160 mg Exemptia at week 0, 80 mg at week 2, and then 40 mg every other week from week 4 to 8. The clinical response andremission were assessed at week 8 using Mayo score. Results: A total of 29 patients (62.1% male; mean age, 34.9 ± 9.7 years)with moderate-to-severe steroid-refractory active UC (mean disease duration, 6.3±5.1 years; pancolitis in 9 patients [31.1%];left-sided colitis in 20 patients [68.9%]) were treated with the Exemptia induction dosing schedule. The mean Mayo score at presentation was 8.2±1.4. At week 8, clinical response was observed in 7 patients (24.1%), whereas clinical remission was observed only in 1 patient (3.5%). Among the non-responders (n=21), 4 patients required colectomy, 1 died, 1 was lost to follow-up, 10 were offered fecal microbiota transplant, 3 were administered infliximab, and 2 patients were administered cyclosporineand tacrolimus, respectively. Four patients (13.8%) developed extrapulmonary tuberculosis. Conclusions: The adalimumab biosimilar Exemptia has limited efficacy for the attainment of clinical response and remission in moderate-to-severe steroid-refractory UC, with a significant risk of acquisition or reactivation of tuberculosis in developing countries such as India.

Incidental benefits after fecal microbiota transplant for ulcerative colitis

( Ramit Mahajan ),( Vandana Midha ),( Arshdeep Singh ),( Varun Mehta ),( Yogesh Gupta ),( Kirandeep Kaur ),( Ritu Sudhakar ),( Anmol Singh Pannu ),( Dharmatma Singh ),( Ajit Sood ) 대한장연구학회 2020 Intestinal Research Vol.18 No.3

Gut dysbiosis can result in several diseases, including infections (Clostridium difficile infection and infectious gastroenteritis), autoimmune diseases (inflammatory bowel disease, diabetes, and allergic disorders), behavioral disorders and other conditions like metabolic syndrome and functional gastrointestinal disorders. Amongst various therapies targeting gut microbiome, fecal microbiota transplantation (FMT) is becoming a focus in the public media and peer reviewed literature. We have been using FMT for induction of remission in patients with moderate to severe active ulcerative colitis (UC) and also for subsequent maintenance of remission. Four cases reported incidental benefits while being treated with FMT for UC. These included weight loss (n = 1), improvement in hair loss (n = 1), amelioration of axial arthritis (n = 1) and improvement in allergic rhinitis (n = 1), thereby suggesting potential clinical applications of FMT in treating extraintestinal diseases associated with gut dysbiosis. (Intest Res 2020;18:337-340)

Maintaining infliximab induced clinical remission with azathioprine and 5-aminosalicylates in acute severe steroid-refractory ulcerative colitis has lower cost and high efficacy (MIRACLE): a multicenter study

( Ramit Mahajan ),( Arshdeep Singh ),( Saurabh Kedia ),( Kirandeep Kaur ),( Vandana Midha ),( Pabitra Sahu ),( Varun Mehta ),( Dharmatma Singh ),( Namita Bansal ),( Khushdeep Dharni ),( Sandeep Kausha 대한장연구학회 2022 Intestinal Research Vol.20 No.1

Background/Aims: Infliximab (IFX) has been used to induce and maintain remission in patients with severe steroid-refractory ulcerative colitis (UC). Long-term use of biologics in developing countries is limited by high cost and frequent side effects. An optimal maintenance strategy in these patients needs to be established. Methods: A retrospective analysis of maintenance of clinical remission with combination of azathioprine (AZA) and 5-aminosalicylates (5-ASA) in patients with severe steroid-refractory UC where IFX (5 mg/kg intravenously at weeks 0, 2, 6) had been used only as an induction therapy was done at 2 centers in India. Primary outcome was the proportion of patients maintaining corticosteroid-free sustained clinical remission (SCR) at the end of study period. Rates of relapse and cost of therapy were also analyzed. Results: Of the 137 patients who received rescue IFX induction therapy, 77 (56.2%) achieved clinical remission (mean age 34.81±13.32 years, 68.83% males, median follow-up 4 years, range 3 months to 6 years) and were included. Cumulative corticosteroid-free SCR was maintained in 68%, 59%, 42%, and 35% patients at 1, 2, 4, and 6 years respectively. Sixty-seven relapses were observed in 33 patients. Majority of the relapses (45/67, 67.16%) occurred within first 2 years of follow-up. Two relapses were managed with re-induction with IFX, one required colectomy, whereas all other responded to repeat course(s) of corticosteroids. Annual per capita maintenance therapy with 5-ASA and AZA was cheaper by US$ 4,526 compared to maintaining remission with IFX. Conclusions: Clinical remission achieved with IFX induction therapy in severe steroid-refractory UC can be sustained over long time with a combination of AZA and 5-ASA. (Intest Res 2022;20:64-71)

Clinical spectrum of elderly-onset inflammatory bowel disease in India

Yogesh Kumar Gupta,Arshdeep Singh,Vikram Narang,Vandana Midha,Ramit Mahajan,Varun Mehta,Dharmatma Singh,Namita Bansal,Madeline Vithya Barnaba Durairaj,Amit Kumar Dutta,Ajit Sood 대한장연구학회 2023 Intestinal Research Vol.21 No.2

Background/Aims: Inflammatory bowel disease (IBD) is increasingly being recognized in elderly patients. Data on clinical spectrum of elderly-onset IBD patients is lacking from India. Methods: A cross-sectional retrospective analysis of a prospectively maintained database of patients diagnosed with IBD was conducted at 2 centers in India. The clinical spectrum of elderly-onset IBD including demographic profile (age and sex), clinical presentation, disease characteristics (disease behavior and severity, extent of disease), and treatment were recorded and compared with adult-onset IBD. Results: During the study period, 3,922 (3,172 ulcerative colitis [UC] and 750 Crohn’s disease [CD]) patients with IBD were recorded in the database. A total of 186 patients (4.74%; 116 males [62.36%]) had elderly-onset IBD (69.35% UC and 30.64% CD). Diarrhea, blood in stools, nocturnal frequency and pain abdomen were the commonest presentations for UC, whereas pain abdomen, weight loss and diarrhea were the most frequent symptoms in CD. For both elderly onset UC and CD, majority of the patients had moderately severe disease. Left-sided colitis was the commonest disease location in UC. Isolated ileal disease and inflammatory behavior were the most common disease location and behavior, respectively in CD. 5-Aminosalicylates were the commonest prescribed drug for both elderly onset UC and CD. Thiopurines and biologics were used infrequently. Prevalence of colorectal cancer was higher in elderly onset IBD. Conclusions: Elderly onset IBD is not uncommon in India. Both the elderly onset UC and CD were milder, with no significant differences in disease characteristics (disease extent, location and behavior) when compared to adult-onset IBD. Colorectal cancer was more common in elderly onset IBD.

Exclusive enteral nutrition for induction of remission in anti-tumor necrosis factor refractory adult Crohn’s disease: the Indian experience

( Ajit Sood ),( Arshdeep Singh ),( Ritu Sudhakar ),( Vandana Midha ),( Ramit Mahajan ),( Varun Mehta ),( Yogesh Kumar Gupta ),( Kirandeep Kaur ) 대한장연구학회 2020 Intestinal Research Vol.18 No.2

Background/Aims: Exclusive enteral nutrition (EEN) is recommended for induction of remission in pediatric Crohn’s disease (CD). However, it is not currently recommended for inducing remission in adults. This report describes the use of 12-week EEN for induction of remission in anti-tumor necrosis factor (anti-TNF) refractory adult CD. Methods: This is a retrospective analysis of adults with moderate to severe active (Crohn’s Disease Activity Index [CDAI] >220) anti-TNF refractory CD, who received EEN for 12 weeks between April 2018 and March 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Primary outcomes included achievement of clinical remission and fistula healing at 12 weeks. Improvement in inflammatory markers and nutritional status were the secondary end points. Results: Out of 23 patients who received anti-TNF agents, 7 (30.4%) were refractory and were offered EEN as a salvage therapy. Six patients (66.7% females, mean age 25.6±6.5 years) consented. Four patients (66.6%) achieved clinical remission (CDAI <150). Mean CDAI of patients decreased significantly after 12 weeks of EEN (388.8±74.8 vs. 160.0±25.2, P< 0.001). Perianal fistulas showed clinical response (drainage decreased by >50%), though none achieved remission. Entero-enteric fistulae showed complete healing. Mean body mass index improved from 15.6±3.1 to 18.9±1.9 kg/m2 at week 12 (P=0.003). Hemoglobin and serum albumin also improved from 8.2±1.1 g/dL and 2.8±0.3 g/dL at baseline to 12.6±0.6 g/dL and 3.6±0.5 g/dL post-EEN respectively (P<0.001 and P=0.006 respectively). Conclusions: EEN appears to be an effective and well tolerated therapy for induction of remission in anti-TNF refractory adult CD. More data from prospective trials with larger number of patients is required. (Intest Res 2020;18:184-191)

Endoscopy for assessment of mucosal healing in ulcerative colitis: time bound or response guided?

Ajit Sood,Ramit Mahajan,Arshdeep Singh,Vandana Midha,Varun Mehta 대한장연구학회 2022 Intestinal Research Vol.20 No.3

The timing of colonoscopy in patients with active ulcerative colitis (UC) lacks coherence. The published guidelines and recommendations advocate time-bound colonoscopy in patients with active UC to assess for mucosal healing. However, the practice of performing colonoscopies at fixed time frames lacks reasoning. The time to achieve mucosal healing in UC is not uniform across the patient populations and is influenced by the disease severity and efficacy and time to therapeutic response of the drugs being used. Additionally, with the availability of sensitive noninvasive inflammatory biomarkers such as fecal calprotectin, that parallel the disease activity and correlate with mucosal healing, the notion of performing colonoscopy at fixed intervals sounds unjustifiable. The authors express their view that a response-guided colonoscopy (driven by normalization of clinical symptoms and inflammatory biomarkers), rather than a time-bound colonoscopy, would be more logical, apart from being cost-effective and patient-friendly.

Trends of inflammatory bowel disease at a tertiary care center in northern India

( Ajit Sood ),( Kirandeep Kaur ),( Arshdeep Singh ),( Vandana Midha ),( Ramit Mahajan ),( Namita Bansal ),( Varun Mehta ),( Dharmatma Singh ) 대한장연구학회 2021 Intestinal Research Vol.19 No.3

Background/Aims: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is increasingly being reported from India and other Asian countries. This study looks into the changing trends of IBD at a tertiary care center in north India over last two decades. Methods: Retrospective analysis of a prospectively maintained database of patients diagnosed with IBD between January 1991 and December 2015 was conducted. The study period was divided into five times cohorts (1991-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015). Results: During the study period, 2,467 patients (UC [n=2,137, 86.6%], CD [n=330, 13.3%], mean age 38.5±13.3 years; 55.9% males) were registered. The proportion of patients with CD increased (ratio of UC to CD declined from 15.7:1 to 4:1). The mean age at diagnosis decreased for UC (45.7±12.1 years in 1991-1995 vs. 37.6±13.0 years in 2011-2015; P=0.001) and remained consistent for CD (41.3±13.6 years in 1996-2000 vs. 41.3±16.9 years in 2011-2015, P=0.86). Patients with proctitis in UC and isolated ileal disease in CD increased over the study period (P=0.001 and P=0.007, respectively). Inflammatory CD increased (P=0.009) whereas stricturing CD decreased (P=0.01) across all cohorts. There was a trend towards less severe presentation of both UC and CD. The use of thiopurines (P=0.02) and biologics increased (P=0.001) with no significant change in trends for requirements of surgery (P=0.9). Conclusions: Increasing prevalence of CD, younger age at diagnosis, diagnosis at an earlier and milder stage, greater use of thiopurines and biologics were observed. (Intest Res 2021;19:282-290)

Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis

( Ajit Sood ),( Ramit Mahajan ),( Garima Juyal ),( Vandana Midha ),( Charanpreet Singh Grewal ),( Varun Mehta ),( Arshdeep Singh ),( Mohan C Joshi ),( Vikram Narang ),( Kirandeep Kaur ),( Hasrat Sidhu 대한장연구학회 2019 Intestinal Research Vol.17 No.1

Background/Aims: Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC. Methods: This was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT. Results: Of 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation. Conclusions: A multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal. (Intest Res 2019;17:78-86)

A simple phenotypic classification for celiac disease

( Ajit Sood ),( Vandana Midha ),( Govind Makharia ),( B. K. Thelma ),( Shivalingappa S Halli ),( Varun Mehta ),( Ramit Mahajan ),( Vikram Narang ),( Kriti Sood ),( Kirandeep Kaur ) 대한장연구학회 2018 Intestinal Research Vol.16 No.2

Background/Aims: Celiac disease is a global health problem. The presentation of celiac disease has unfolded over years and it is now known that it can manifest at different ages, has varied presentations, and is prone to develop complications, if not managed properly. Although the Oslo definitions provide consensus on the various terminologies used in literature, there is no phenotypic classification providing a composite diagnosis for the disease. Methods: Various variables identified for phenotypic classification included age at diagnosis, age at onset of symptoms, clinical presentation, family history and complications. These were applied to the existing registry of 1,664 patients at Dayanand Medical College and Hospital, Ludhiana, India. In addition, age was evaluated as below 15 and below 18 years. Cross tabulations were used for the verification of the classification using the existing data. Expert opinion was sought from both international and national experts of varying fields. Results: After empirical verification, age at diagnosis was considered appropriate in between A1 (<18) and A2 (≥18). The disease presentation has been classified into 3 types-P1 (classical), P2 (non-classical) and P3 (asymptomatic). Complications were considered as absent (C0) or present (C1). A single phenotypic classification based on these 3 characteristics, namely age at the diagnosis, clinical presentation, and intestinal complications (APC classification) was derived. Conclusions: APC classification (age at diagnosis, presentation, complications) is a simple disease explanatory classification for patients with celiac disease aimed at providing a composite diagnosis. (Intest Res 2018;16:288-292)

Clinical profile and outcomes of opioid abuse gastroenteropathy: an underdiagnosed disease entity

( Ramit Mahajan ),( Yogesh Gupta ),( Arshdeep Singh ),( Pulkit Dhiman ),( Vandana Midha ),( Chandan Kakkar ),( Vikram Narang ),( Varun Mehta ),( Kavita Saggar ),( Ajit Sood ) 대한장연구학회 2020 Intestinal Research Vol.18 No.2

Background/Aims: Opioid-induced bowel dysfunction includes nausea, vomiting, constipation and abdominal distension. We describe patients presenting with gastrointestinal (GI) ulcers and ulcerated strictures secondary to opioid abuse, an entity not well described in literature. Methods: This retrospective observational study included patients with opioid abuse gastroenteropathy presenting to Dayanand Medical College and Hospital, Ludhiana, India between January 2013 and December 2018. Opioid abuse gastroenteropathy was defined as gastric or small bowel ulcers and ulcerated strictures in patients abusing opioids, where all other possible etiologies of GI ulcers/strictures were excluded. Clinical, biochemical, endoscopic, radiological and histological parameters as well as response to treatment were assessed. Results: During the study period, 20 patients (mean age, 38.5±14.2 years; 100% males) were diagnosed to have opioid induced GI ulcers and/or ulcerated strictures. The mean duration of opioid consumption was 6.2±3.4 years. The mean duration of symptoms at presentation was 222.1±392.3 days. Thirteen patients (65%) had gastroduodenal involvement, 6 (30%) had a jejunoileal disease and 1 (5%) had an ileocecal stricture. Two patients (10%) presented with upper GI bleeding, 11 (55%) had features of gastric outlet obstruction and 7 (35%) presented with small bowel obstruction. Abdominal pain and iron deficiency anemia were the most common presentations. Only 1 patient (5%) responded to proton pump inhibitors, 3 (15%) had a lasting response to endoscopic balloon dilatation, while all other (80%) required surgical intervention. Conclusions: Opioid abuse gastroenteropathy presents as ulcers and ulcerated strictures which respond poorly to medical management and endoscopic balloon dilatation. A majority of these cases need surgical intervention. (Intest Res 2020;18:238-244)