Background: Crohn's disease (CD) is characterized by granulomatous inflammation of the digestive tract. Diagnosing CD involves assessing clinical symptoms, radiological and endoscopic findings, and histopathological evidence. Although previously considered a disease in developed countries, CD is increasing in developing nations, but challenges exist in diagnosing CD promptly. This study aims to report diagnostic parameters for early and correct CD diagnosis in Pakistan.
Methodology: A retrospective analysis from June 2016 to August 2023 of 22 CD patients was done, by data from medical records, questionnaires completed at diagnosis, and telephonic interviews. Baseline demographic and clinical characteristics were assessed, and patients were categorized using the Montreal classification.
Results: CD was diagnosed in 22 patients, with a 1:1 male-to-female ratio with a mean age of 33 years (range 15-55 years). Symptoms at presentation included abdominal pain (95.5%), watery diarrhea (86.4%), fever (31.8%), rectal bleeding (54.5%), and weight loss (81.8%) with 68% having symptoms for over 12 months before diagnosis. Disease characteristics were diverse, with various patterns of involvement and histopathological findings.
Conclusions: In resource-limited countries like Pakistan, the timely diagnosis of CD presents a significant healthcare challenge. Therefore, it is necessary to tackle these complex problems by enhancing diagnostic capabilities, raising medical awareness, and improving access to healthcare resources.
Background: Fecal calprotectin (FC) is a reliable predictor of active bowel inflammation in postoperative Crohn's disease (CD), but cutoffs vary between studies. Recent guidelines recommend a cutoff of <50 ug/g to avoid routine endoscopy in patients at low pretest probability for CD recurrence. We evaluated the performance of this threshold in a real-world CD cohort after ileocolic resection (ICR).
Methods: In this retrospective study, patients with CD post-ICR between 2009 to 2020 with FC > 60 days but < 1 year of surgery were included from a multicenter database. Established risk factors and/or biologic prophylaxis (biologic within 90 days of surgery) defined pretest probability. Those without postoperative colonoscopy were excluded. Rates of endoscopic recurrence, defined as Rutgeerts score ≥ i2b at any time after surgery, were compared between FC < 50 versus ≥ 50 ug/g. Student's t-test and Fisher's exact test were utilized for statistical analysis. All postoperative FCs were matched to closest colonoscopy within 1 year to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
Results: Thirty-seven patients categorized as either low-risk or high-risk and received biologic prophylaxis and had postoperative colonoscopy were included. Median time to first FC was 217 days (IQR 131-288). 15 (41%) patients had initial FC < 50 ug/g versus 22 (59%) ≥50 ug/g. Median time to first colonoscopy was 234 days (IQR 189-369). Compared to initial FC ≥ 50 ug/g, FC < 50ug/g experienced less endoscopic recurrence (0% vs. 36%, P = .005). Median time to first endoscopic recurrence in FC ≥ 50 ug/g was 145 days. There were 39 matched pairs of FC and colonoscopy. At an FC cutoff of 50 ug/g, calculated sensitivity was 90% and NPV was 93%, whereas specificity and PPV were 48% and 38%, respectively.
Conclusions: In this real-world cohort, FC < 50 ug/g is a useful cutoff to exclude endoscopic recurrence in a post-ICR CD population that is at low pretest probability of recurrence.
Background: Cytomegalovirus (CMV) can be reactivated in ulcerative colitis (UC), but its role in progression of inflammation is unclear. Risk factors include severe colitis and treatment with immunosuppressive medications, particularly corticosteroids and immunomodulators.
Methods: We report a case of cytomegalovirus colitis in a pediatric patient with pancolitis who had been refractory to aminosalicylate, infliximab, and ustekinumab and was in clinical remission and with transmural response on upadacitinib.
Results: This is a case of a 13-year-old male with UC refractory to multiple therapies who were in clinical remission on upadacitinib 30 mg daily. He developed an acute increase in symptoms and did not respond to therapy escalation with increased upadacitinib 45 mg daily for 2 weeks and prednisone for 1 week. He was diagnosed with cytomegalovirus colitis on flexible sigmoidoscopy biopsy. He was treated with intravenous ganciclovir with tapering of immunosuppressive regimen. Despite initial response, he underwent subtotal colectomy and subsequent restorative proctocolectomy with ileal pouch anal-anastomosis.
Conclusions: Despite our patient having multiple risk factors for developing CMV colitis, upadacitinib may have played a role when considering its known impact on the herpes family of viruses. CMV colitis should be evaluated for in any patient who presents with worsening symptoms without evidence of other infection or response to increase in therapy.
Background: Vedolizumab has since 2021 been available as a subcutaneous formulation. We aimed to assess 18-month drug persistence and possible predictive factors associated with discontinuation, safety, serum drug profile, drug dosing, and disease activity in a real-world cohort of patients with inflammatory bowel disease switched from intravenous to subcutaneous vedolizumab maintenance treatment.
Methods: Eligible patients were switched to subcutaneous vedolizumab and followed for 18 months or until discontinuation of subcutaneous treatment. Data on preferred route of administration, adverse events, drug dosing, serum-vedolizumab, disease activity, fecal calprotectin, and C-reactive protein were collected. Persistence was described using Kaplan-Meier analysis. The impact of clinical and biochemical variables on persistence was analyzed with Cox proportional hazard models.
Results: We included 108 patients, and the estimated 18-month drug persistence was 73.6% (95% CI [64.2-80.1]). Patients in clinical remission at switch were less likely to discontinue SC treatment (HR = 0.34, 95% CI [0.16-0.73], P = .006), and patients favoring intravenous treatment at switch were almost 3 times more likely to discontinue (HR = 2.78, 95% CI [1.31-5.90], P = .008). Four patients discontinued subcutaneous vedolizumab due to injection site reactions. At 18 months, 88% of patients administered subcutaneous vedolizumab with an interval of ≥ 14 days, and serum-vedolizumab was 39.1 mg/L. Disease activity was stable during follow-up.
Conclusions: Three of the four patients remained on subcutaneous vedolizumab after 18 months, a large proportion received treatment at standard dosing intervals, and disease activity remained stable. This indicates that switching from intravenous to subcutaneous vedolizumab treatment is convenient and safe.
Background: Partial enteral nutrition (PEN) is a well-established treatment for children with Crohn's disease (CD). However, its efficacy in adults with CD remains uncertain. We aimed to assess the effectiveness of PEN as an add-on to escalated biological therapy in adults with CD who have lost response to biologics.
Methods: We conducted a retrospective observational study including patients who had lost response to biologics and received PEN in combination with escalated treatment, compared to those treated only with escalated therapy. The primary endpoint was steroid-free clinical remission (CR) at 24 weeks. Secondary endpoints included transmural healing (TH) and response (TR) rates along with selected clinical outcomes.
Results: Forty-two patients were screened; 12 (28.6%) were excluded for complicated disease and 30 (71.4%) were included in the final analysis. Fourteen (46.7%) patients completed PEN treatment at 8 weeks, while 16 patients (53.3%) discontinued treatment due to intolerance and continued with escalation of biologic (BT group). At 24 weeks, 9 patients (64.3%) in the PEN group achieved CR, compared to 4 patients (25%) in the BT group (P = .03). The TR rate was 64.9% in the PEN group and 25% in the BT group (P = .03). Patients receiving PEN exhibited an increase in albumin levels compared to those in the BT group (Δ = 0.5; P = .02). A higher rate of therapy changes (68.7%) was observed in the BT group compared to 14.2% in the PEN group (P = .004). Prior failure to 2 lines of biological therapy was associated with adherence to PEN (OR = 1.583; CI = 1.06-2.36; P = .01).
Conclusions: In patients who had lost response to biologics, PEN in combination with escalated biologics was associated with CR and TR and improved nutritional status. Hence, the addition of PEN should be considered for patients with difficult-to-treat CD.
Background: Ulcerative colitis (UC) causes long-lasting inflammation and ulcers in the gut. Limited observational data are available linking dietary magnesium intake and UC. In the present study, we aimed to investigate the association between dietary magnesium intake and UC in adults.
Methods: The current population-based case-control study was performed on 109 UC patients and 218 age (±2 years) and sex-matched controls. The diagnosis of UC was made according to the standard criteria by a gastroenterology specialist. Dietary intakes were assessed using a validated self-administrated 106-item dish-based Food Frequency Questionnaire (FFQ). We also used a pretested questionnaire to collect data on potential confounders.
Results: Individuals in the top tertile of magnesium intake were less likely to have UC compared with those in the bottom tertile. A significant inverse relationship was found between dietary magnesium intake and UC (odds ratio [OR]: 0.32, 95% confidence interval [CI]: 0.18-0.59) in the crude model. This relationship was also observed when we took several potential confounding into account (OR: 0.30, 95% CI: 0.14-0.68).
Conclusions: Adherence to a magnesium-rich diet may have a role in preventing UC. However, further studies are needed to confirm our findings.
Background: Prior authorizations are generally required by insurers for gastroenterologists to prescribe biologics and small-molecule drugs to treat inflammatory bowel disease (IBD). Authorization denials occur in a wide variety of clinical scenarios, including denials of standard and nonstandard medication dosing.
Methods: We performed a national cross-sectional survey on a broad variety of specific clinical scenarios to assess experience and opinions on whether or not insurance authorization denials are in accordance with clinical expertise.
Results: Eighty-four gastroenterologists completed the survey. Denial experience was common for infliximab dose modifications, vedolizumab dose modifications, ustekinumab first-time therapy, and maintenance dosing. The bulk of disagreement with authorization denials involved scenarios of dose escalation and re-induction guided by both loss of clinical response and/or therapeutic drug monitoring, denial of re-authorizations of stable dosing, and use of non-anti-TNFs in specific patient populations including the elderly and patients with multiple comorbidities. Respondents unanimously agreed that insurance companies do not play an adequate role in helping patients obtain PA. Furthermore, most of the respondents agree that to decrease the burden of the PA process, peer-peer processes should be between other IBD-trained providers who understand these complex treatment strategies.
Conclusions: Our cross-sectional survey highlights the degree of discordance in clinical decision-making between insurers and gastroenterologists. Further engagement between gastroenterologists and insurers is needed to foster common understanding on these discordant authorization denials in these real-world clinical IBD scenarios.