This was a systematic review and meta-analysis that included 46 studies.
Key findings: In 9,447 subjects who were completely vaccinated, the pooled seroconversion relative risk was 0.96 (95%CI, 0.94-0.97), and was higher for mRNA vaccines (0.97, 95%CI 0.96-0.98) than for adeno-associated vaccines (0.87, 95%CI: 0.78-0.93)
The pooled seroconversion rates were similar regardless of IBD therapy, and ranged from 0.93 to 0.99.
The pooled relative risk of breakthrough COVID-19 infections in vaccinated patients with IBD was not significantly different from that of vaccinated controls. However, a decay in antibody titers after 4 weeks from vaccination appeared to be accelerated in those on anti-TNF agents, immunomodulators or their combination.
My take: IBD patients benefit from complete COVID-19 vaccination similar to healthy controls.
Using a case-control design, the authors found that complete (2 dose) vaccination during pregnancy —Key findings:
The effectiveness of maternal vaccination against hospitalization for Covid-19 among infants < 6 months was 52% overall, 80% during the delta period, and 38% during the omicron period.
My take: Vaccination protects mother and infant. “Maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than 6 months of age.”
For the issue of fatigue and IBD, besides active IBD and anemia, the authors recommend considering medication side effects (especially from immunomodulators/corticosteroids and cannabis), mental health, sleep disorders, and nutritional concerns (?role for thiamine supplementation). Even when all these issues are addressed, many times fatigue persists.
Here is the proposed algorithm from July 24, 2020.
#MondayNightIBD has a lot of topics that they have covered including functional medicine, COVID, sexual health, utilizing social medicine, grief and pharmacology.
Data pooled from 27 studies showed the prevalence of NAFLD among IBD patients was 32% (substantial heterogeneity); this is “statistically significantly higher than the prevalence of NAFLD in the general population (25.2%; P < 0.001)”
A total of 93 studies were identified, comprising 16,064 IBD patients with co-occurring IMIDs and 3,451,414 IBD patients without IMIDs. IMIDs included the following:
Unspecified autoimmune disease
Diabetes type 1
Primary Sclerosing Cholangitis
Giant cell arteritis
Primary biliary cholangitis
Key findings: Patients with IBD and co-occurring IMIDs were at increased risk of having extensive colitis or pancolitis (risk ratio, 1.38; 95% Cl, 1.25–1.52; P < 0.01, I2 = 86%) and receiving IBD-related surgeries (risk ratio, 1.17; 95% Cl, 1.01–1.36; P = 0.03; I2 = 85%) compared with patients without IMIDs
In a prospective study with 171 adults with IBD in remission, the authors combined
measures of psychological comorbidities and quality of life (QoL)
microbial analysis with 16S rRNA high-throughput sequencing
Microbiomes of patients with higher perceived stress had significantly lower alpha diversity
Anxiety and depressive symptoms were significantly associated with beta diversity
My take: This study adds another dimension to the idea of bidirectionality between psychological well-being and course of inflammatory bowel disease. The microbiome may directly influence both psychological well-being and IBD activity.
Eight PIBD children had COVID-19 globally, all with mild infection without needing hospitalization despite treatment with immunomodulators and/or biologics. ..
Preliminary data for PIBD patients during COVID-19 outbreak are reassuring. Standard IBD treatments including biologics should continue at present through the pandemic, especially in children who generally have more severe IBD course on one hand, and milder SARS-CoV-2 infection on the other.
A recent study (G D’Haens, O Kelly, R Battat et al. Gastroenterol 2020; 158: 515-26,editorial 463) describes the development and validation of a blood test panel to assess Crohn’s disease (CD) endoscopic activity level. The authors evaluated a blood test which measured 13 proteins in the blood using samples from 278 patients. Then there were two validation cohorts:
116 biologic-naive CD patients -cohort 1
195 biologic-exposed CD patients -cohort 2
The blood tests were used to develop an endoscopic healing index (EHI) score (0-100). Higher scores indicate greater disease activity.
EHI values below 20 identified remission with a sensitivity of 97.1% and 83.2% in cohorts 1 & 2 respectively; specificity was 69% and 37% respectively.
EHI values below 50 points identified patients with highest specificity of 100% and 88% in cohorts 1 and 2 respectively.
EHI AUROC (area under the receiver operating characteristic curve) did not differ significantly from that of fecal calprotectin and were higher than measurement of serum CRP (in cohort 1 but not cohort 2).
The editorial notes that the EHI performed much better in younger, biologically-naive patients and that the EHI could potentially be incorporated into a treat-to-target strategy which would potentially entail followup endoscopy in those with EHI >50.
My take: While the stool calprotectin has some logistical barriers in many patients, the EHI is likely a much more expensive test and needs further validation. For now, the combination of CRP and calprotectin are the best noninvasive biomarkers to assess CD activity.
Briefly noted: Vedolizumab-Induced Pulmonary Toxicity -Case report of a patient with ulcerative colitis who developed interstitial lung disease (Gastroenterol 2020; 158: 478-9).
A recent single-center study (AW Fondell et al. Inflamm Bowel Dis 2020; 26: 635-40, editorial by Joel Rosh, 641-2) examined the first-year costs of children with inflammatory bowel disease (IBD) in 2016. There were 67 patients (43 with Crohn’s disease (CD), and 24 with ulcerative colitis (UC)).
Mean cost was $45,753; $43,095 for CD, $50,516 for UC
Severe CD (n=11) was $71,176 and severe UC (n=5) was $134,178; it is notable that only one patient with CD had surgery and only one patient with UC had surgery.
69% of CD patients and 33% of UC patients received biologics
21% (n=9) of CD patients and 45% (n=11) of UC patients were hospitalized
Private payer reimbursement was a mean of $51,269 compared to $24,610 mean for Medicaid.
In any cost analysis, many assumptions are needed. For medications, for example, the author used pharmaceutical retail prices. The actual costs are near-impossible to calculate as every insurance policy and every hospital system has a multitude of charges based on proprietary negotiations.
While this data comes from a referral center, all of the patients in the study were from Connecticut.
Due to the expense of care, Dr. Rosh points out that many insurers have often mandated the use of “standard dosing” of biologic therapy, “ignoring that robust data” indicate that this dosing is “the exception rather than the rule in pediatric IBD patients.” These type of short-sighted interventions could affect long-term medical outcomes.
My take: There clearly are areas where costs can be reduced (eg. lower infusion costs, lower endoscopy costs, biosimilars). However, no amount of cost cutting will change the conclusion that good care for IBD is expensive.
Briefly noted: TS Kafil et al. Inflamm Bowel Dis 2020; 26: 502-9. This study examined evidence for cannabis effectiveness in IBD. After performing a literature search, the authors could only identify five randomized controlled trials (n=185). Each study used different doses, formulations and routes of administration. No studies evaluated maintenance treatment and relapse in CD or UC. Findings: “no firm conclusions can be made regarding the safety and effectiveness of cannabis and cannabionoids in adults with CD and UC.”
Two articles describe both increasing and decreasing trends in the prevalence of inflammatory bowel disease (IBD).
Y Ye et al. Inflamm Bowel Dis 2020; 26: 619-25, editorial 626-27
M Torabi et al. Inflamm Bowel Dis 2020; 26: 581-90, editorial 591-92
The first study by Ye et al provides the familiar message that IBD prevalence has been increasing in pediatrics and adults. This study examined 2 large claims databases. The Optum database covered ~18 million annually during the study period (total ~57 million from 2007-2017) and Truven covered ~44 million annually (total ~240 million since 1995)
Pediatric IBD prevalence increased by 133% from 2007 to 2016: from 33 per 100,000 to 77 per 100,000. Crohn’s disease (CD) was twice as prevalent as ulcerative colitis (UC) in the pediatric population (46 vs 22)
Adult IBD prevalence increased by 123% from 2007 to 2016: from 215 per 100,000 to 478 per 100,000. The prevalence rates of CD and UC were similar in adults: 198 vs 181)
The Northeast region had the highest prevalence of IBD, followed by Midwest, South and then West.
Based on these prevalence data, there are an estimated 58,000 children (2-17) and 1.2 million adults with IBD in U.S. Or, 1 in 1299 children and 1 in 209 adults.
Diagnosis and data derived from claims database
Cases can vary significantly based on how sensitive the definition for IBD is in a given study. In this study, the authors indicate in supplementary material, that the prevalence rates could be doubled in adults if they chose a more sensitive/less specific case definitions.
The second study by Torabi et al, which utilized the Manitoba Epidemiology Database (n=1.2 million) showed a decrease in IBD incidence. The authors examined 296 small geographic areas (SGAs) and found that many had persistently high IBD incidence rates.
The incidence of IBD decreased from 1990 when it was 23.6 per 100,000 to 16.2 per 100,000 in 2012.
In the study period (1990-2012), there were 3114 cases of CD and 3499 cases of UC diagnosed in Manitoba
In the discussion, the authors speculate on the reasons for the decline in IBD incidence in an area with high rates of IBD. Some of the change may be related to changes in the population mix –more immigrants from areas with lower rates of IBD. In the editorial, it is noted that a recent systematic review (Lancet 2018; 390: 2769-78) indicated that the “incidence of IBD is stabilizing in Western countries.”
My take: There are a lot kids and adults with IBD. The preponderance of epidemiology studies point to increasing incidence and prevalence.
A recent study (AKN Pedersen et al. JPEN https://doi.org/10.1002/jpen.1593) shows the utility of obtaining urine spot sodiums in patients with an ileostomy. Thanks to Kipp Ellsworth for sharing this reference.
Background: Sodium deficiency in patients with an ileostomy is associated with chronic dehydration and may be difficult to detect. We aimed to investigate if the sodium concentration in a single spot urine sample may be used as a proxy for 24‐hour urine sodium excretion.
Design: In this prospective, observational study, we included 16 adult individuals: 8 stable patients with an ileostomy and 8 healthy volunteers with intact intestines
There was a high and statistically significant correlation between 24‐hour natriuresis and urine sodium concentrations in both morning spot samples (n = 8, Spearman’s rho [ρ] = 0.78, P = 0.03) and midday spot samples (n = 8, ρ = 0.82, P = 0.02) in the patients with an ileostomy.
My take: In patients with ileostomy (and also short bowel syndrome), periodic urine sodium values (from morning or mid-day) will help detect subclinical sodium depletion.