“The overall incidence of MC in Olmsted County, MN, increased from 1985 to 2001, stabilized between 2002 and 2010, and continues to show a plateau between 2011 and 2019.”
Medications associated with a risk of microscopic colitis (MC) include statins, SSRIs, PPIs, aspirin, other NSAIDs, and histamine H2-receptor antagonists within 3 months of diagnosis. “A recent US multicenter cohort study found an inverse association with PPIs and histamine H2-receptor antagonists when compared with controls with chronic diarrhea; only NSAID use was associated with MC. 31 It is plausible these medications do not cause MC, but instead aggravate diarrhea and bring the diagnosis to clinical attention.”
Methods: Ulcerative colitis patients who failed anti-TNF treatment and initiated vedolizumab (n=83) or tofacitinib (n=65) treatment, were identified in the ICC Registry in the Netherlands.
Key findings:
Tofacitinib treated patients were more likely to achieve corticosteroid-free clinical remission and biochemical remission at week 12, 24 and 52 compared to vedolizumab treated patients (OR: 6.33, OR: 3.02, and OR 1.86 and OR: 3.27, OR: 1.87, and OR:1.81, respectively).
There was no difference in infection rate or severe adverse events.
My take: The response rates with tofacitinib were significantly better than vedolizumab at all time points; however, by 52 weeks, the differences were less pronounced. Nevertheless, the safety profile of vedolizumab is much more favorable than tofacitinib and this is a very important consideration.
– Third approved indication for SKYRIZI (risankizumab-rzaa) is supported by safety and efficacy data from two induction and one maintenance clinical trials evaluating SKYRIZI in moderately to severely active Crohn’s disease, ADVANCE, MOTIVATE and FORTIFY1-4
– As early as week 4 in the induction studies, clinical response and clinical remission were achieved by significantly more subjects treated with SKYRIZI versus placebo, as were co-primary endpoints of endoscopic response and clinical remission at week 12 and week 521-4
About SKYRIZI® (risankizumab-rzaa) SKYRIZI is an interleukin-23 (IL-23) inhibitor that selectively blocks IL-23 by binding to its p19 subunit.9,10 IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases, including Crohn’s disease.10 The approved dose to treat adults with moderately to severely active Crohn’s disease is 600 mg administered by intravenous infusion over at least one hour at week 0, week 4, and week 8, followed by 360 mg administered by subcutaneous injection at week 12, and every 8 weeks thereafter.4 SKYRIZI is also approved in the U.S. to treat moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, as well as to treat active psoriatic arthritis in adults, and the recommended dosage is 150 mg administered by subcutaneous injection at week 0, week 4, and every 12 weeks thereafter.4 Phase 3 trials of SKYRIZI in psoriasis, Crohn’s disease, ulcerative colitis and psoriatic arthritis are ongoing
Many times, treatment decisions are like on “Let’s Make a Deal.” That is, should I stick with what I’ve got or should I try for something better & sometimes wind up with a goat. In this referenced article, patients were under maintenance therapy with adalimumab (ADA) monotherapy (40 mg every 14 days) and had experienced a secondary loss of response (LOR) despite trough levels > 4.9 μg/mL. In this nonrandomized prospective study, patients were either swapped to vedolizumab (VDZ) or optimized on adalimumab (ADA) treatment.
Key findings:
At 24 months, 11 out of 70 patients (16%) in the swap group discontinued treatment compared with 36 out of 61 (59%) patients in the optimization group (P < 0.001)
In the optimization group, treatment discontinuation was positively associated with baseline fecal calprotectin >500 μg/g (HR, 3.5)
In patients selected for optimization, 56% (34/61) remained on ADA at 1 year and 41% (25/61) at 2 years
In their discussion, the authors state “current guidelines recommend switching to another class of biologics in case of LOR to ADA with therapeutic drug levels.” However, the authors note that their therapeutic level cut-off of >4.9 mcg/mL is lower than the latest recommendations. In addition, in their conclusion, they note that due to limited biologic options, “ADA optimization strategy might be considered” in a subgroup.
My take: Despite better results in the patients that swapped to VDZ in this study, I think it is important to assure adequate drug levels before choosing a new drug class. For ADA, expert recommendations have suggested a level of 8-12 as therapeutic and to avoid discontinuation if ADA level is less than 10. In this study, more than 40% remained on ADA two years after LOR in those with dosing optimization.
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Research has shown that IUS has the potential to be a valuable additional point-of-care tool to guide treatment choice and to monitor and predict treatment response, although evidence of its accuracy and value in clinical practice is still limited
The utility may be operator-dependent as well
My take: Due to low upfront costs, IUS would be appealing adjunct to current monitoring. However, one could envision IUS leading to more downstream studies (& costs), especially if its sensitivity and specificity are not very high.
In this internet-based cohort of 9-17 yr olds (n=159, 96% white), the authors found no association between baseline PROMIS Pediatric anxiety score and subsequent sCDAI (change in sCDAI for 3-point change in PROMIS Pediatric −0.89; 95% CI −4.81 to 3.03). This study is in contrast to studies in adults which have shown a bidirectional relationship between anxiety/depression and IBD activity.
My take: It is difficult to know with certainty whether anxiety/depression may trigger IBD activity; more studies are needed. Treatment of mental health is important regardless of its effects on IBD activity.
This lengthy article describes the emerging therapy of virtual reality to help with chronic pain. Some of the article focuses on chronic abdominal pain.
Here are some excerpts:
Brennan Spiegel, a gastroenterologist and researcher at Cedars-Sinai .. runs one of the largest academic medical initiatives studying virtual reality as a health therapy…
As Daniel Clauw, who runs the Chronic Pain and Fatigue Research Center at the University of Michigan, put it in a 2019 lecture, there isn’t “any drug in any chronic-pain state that works in better than one out of three people.” He went on to say that nonpharmacological therapy should instead be “front and center in managing chronic pain — rather than opioids, or for that matter, any of our drugs…”
[In one] virtual environment … built specifically for patients with chronic gastrointestinal symptoms…[the patient] used hand controls. Inside a virtual clinic, a robot named Maia — short for “mixed-reality artificial-intelligence assistant” — guided her to a young blond woman, who expressed frustration with abdominal symptoms. [The patient] examined the [virtual] patient with her virtual hands, placing a stethoscope on her stomach to listen to the sounds of digestion. Maia explained how the brain and the gut work together. As she spoke, an image of a brain popped up, connected to intestines by a yellow flashing line. When the brain became stressed, it turned fuchsia in color, and the yellow line to the gut metamorphosed into a stream of fire...
Scientists knew that the brain has some control over pain, but that insight was mostly confined to the situations described by Patrick Wall’s and Ronald Melzack’s gate-control theory, which helps explain why, say, a person running from a house on fire may not realize that she sprained her ankle until she is a safe distance away. The brain, so intent on escaping the fire, shuts the gate, blocking pain signals coming up the spinal cord from the ankle. “You could close the gate,” says Clifford Woolf, a neurobiology professor at Harvard Medical School who worked in Wall’s lab, but “essentially there was nothing about the opposite possibility — which is that the brain, independent of the periphery, could be a generator of pain.”
“Woolf was conducting his own experiment in Wall’s lab, applying painful stimuli to rats’ hind legs. The animals developed large “fields” of pain that could easily be activated months later with a light tap or gentle warmth, even in spots that weren’t being touched directly. “I was changing the function of the nervous system, such that its properties were altered,” Woolf says. “Pain was not simply a measure of some peripheral pathology,” he concluded; it “could also be the consequence of abnormal amplification within the nervous system — this was the phenomenon of central sensitization.”
V.R.’s “unique ability to convey a sense of just ‘being there,’ wherever there happens to be,” as he [Spiegel] puts it in his book “VRx: How Virtual Therapeutics Will Revolutionize Medicine.” “All of its revolutionary potential tumbles out of its ability to compel a person’s brain and body to react to a different reality.”
RelieVRx also has modules that prompt patients to redirect their attention through game play or by allowing scenes — waves washing onto a sunny coast, say — to soothe their nervous systems. The average session lasts seven minutes, and patients are directed to do just one a day for eight weeks…
A recently published study by researchers affiliated with the company [AppliedVR], for which they recruited subjects during the pandemic through Facebook ads and pain organizations, reported an average drop in chronic back pain by nearly 43 percent for the RelieVRx group compared with 25 percent for the control group. For those who used RelieVRx, pain also interfered less with their activity and sleep. Three months after the last V.R. session, these gains were mostly found to endure…
In chronic pain, the body part that hurts may be undamaged and even seem healthy; what’s altered is the area of the brain that corresponds to its anatomical location...
If doctors do start prescribing V.R., there’s another hurdle to clear: Who will pay for it?
My take: I am looking forward to the pediatric studies which will be needed before this technology can be promoted. I would think pediatric patients with chronic pain may respond even more favorably than adults. If this technology were in our clinic, I am certain that are “no show” rate would be lower.
A 50 year old with a history of abdominal distention for a week and chronic constipation had a CT with intravenous contrast. Ultimately he had a disimpaction under general anesthesia and a flexible sigmoidoscopy.
My view: A complete examination with digital rectal exam (if feasible) or an AXR would have been sufficient for diagnosis.
Biosimilar utilization initiation increased from a baseline of 1% in June 2019 to 96% by February 2021 among eligible patients; 20% of all patients (n-98) had insurance which preferred originator product
Estimated cost savings over the project duration were nearly $381,000 (average sales price) over the 20 month study
My take: The introduction of biosimilars have resulted in huge cost savings. In addition, for infliximab, the originator product price has also dropped substantially (more than 60% in some locations)
Methods: This was a prospective multicenter cohort study of adult IBD patients (n=176) who underwent 2 switches from the originator IFX to CT-P13 to SB2 (group 1), 1 switch from CT-P13 to SB2 (group 2), and 1 switch from the originator IFX to CT-P13 (group 3).
Key findings:
At 12 months after the most recent switch 76.9% (40 of 52, group 1), 65.7% (46 of 70, group 2) and 76.9% (20 of 26, group 3) of patients were in clinical remission. Treatment persistence at 12 months was 85.0%, 87.0%, and 70.1%, respectively.
There were no significant differences in the rate of clinical, CRP, FC remission, or treatment persistence at 12 months between the 3 groups.
My take: This study did not identify detrimental effects from multiple successive switching and switching between biosimilars of IFX. Longer followup and more clinical experience will be needed to confirm these findings.
Background: Guselkumab, a selective p19 interleukin-23 antagonist, is approved for the treatment of plaque psoriasis and psoriatic arthritis.
Methods: GALAXI-1, a phase 2, double-blind, placebo-controlled study, randomized patients with moderate to severe Crohn’s disease 1:1:1:1:1 to intravenous guselkumab 200 mg, 600 mg, or 1200 mg at weeks 0, 4, and 8; intravenous ustekinumab approximately 6 mg/kg at week 0 and 90 mg subcutaneously at week 8; or placebo. n=309 with ~50% having disease refractory to prior biologics
Key findings:
At week 12, significantly greater reductions in Crohn’s Disease Activity Index from baseline (least squares means: 200 mg: –160.4, 600 mg: –138.9, and 1200 mg: –144.9 vs placebo: –36.2; all, P < .05) and significantly greater proportions of patients achieved clinical remission in each guselkumab group vs placebo
Improvement compared to placebo was evident as early as week 4
Safety event rates were generally similar across treatment groups
My take: This is an exciting time for practitioners taking care of patients as there are an increasing number of pharmacologic and dietary treatments for inflammatory bowel disease. With guselkumab, there may be an overlapping mechanism with ustekinumab which targets IL-12/23.
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