Tag Archives: subcutaneous

SC Infliximab versus Vedolizumab for Crohn’s Disease and for Ulcerative Colitis

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Peyrin‐Biroulet, L., Arkkila, P., Armuzzi, A. et al. BMC Gastroenterol 24, 121 (2024). https://doi.org/10.1186/s12876-024-03163-5. Open Access! Comparative efficacy and safety of subcutaneous infliximab and vedolizumab in patients with Crohn’s disease and ulcerative colitis included in randomised controlled trials. 

Methods: Studies included in the current analysis were parallel-group, randomised controlled trials (RCTs) that evaluated treatment with IFX SC, following induction therapy with IFX IV, or treatment with VDZ (either with VDZ IV or with VDZ SC [following IV induction therapy]). The authors identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ.

Key findings:

Crohn’s disease: Intravenous induction therapy with IFX demonstrated better efficacy compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year.

Comparison of IFX SC versus VDZ for key efficacy outcomes in patients with Crohn’s disease

Ulcerative colitis: Efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year.

Comparison of IFX SC1 versus VDZ for key efficacy outcomes in patients with ulcerative colitis

Safety: In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year.

Discussion Points:

  • The authors discuss some limitations of their study. “The GEMINI I, GEMINI II, and VISIBLE 1 trials were rated as being at high risk of bias for the category ‘other’ bias, because only patients who achieved a clinical response during induction went on to participate in the maintenance phase, which could potentially lead to a higher estimate of efficacy during the maintenance phase than if patients who did not achieve a clinical response were also included.”
  • The vedolizumab studies notably included a high proportion of patients who failed to respond to anti-TNFs. “All VDZ studies permitted enrolment of patients with prior TNFi failure, accounting for 47.5% of VDZ-treated patients overall.” Thus, in a true head-to-head study with patients unexposed to biologics, VDZ may achieve better results.

My take: This study indicates that SC infliximab (like IV infliximab) appears to be more effective than vedolizumab for patients with Crohn’s disease and similarly effective for ulcerative colitis, keeping in mind the aforementioned discussion points. While not evident in this study, vedolizumab has a superior safety profile.

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Vedolizumab and Infliximab: Expected Dosing When Switching From IV to SC Routes

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Z Wang et al. Clin Gastroenterol Hepatol 2023; 3188-3190. Therapeutic Drug Monitoring Can Guide the Intravenous-to-Subcutaneous Switch of Infliximab and Vedolizumab: A Simulation Study

The authors performed population pharmacokinetic (popPK) simulations to determine optimal dosing recommendations.

Key points:

  • Infliximab: “The Q2W SC dosing regimen of infliximab has been selected with the purpose of exceeding a C,trough,ss of 5 mg/L.” This tends to align with 5 mg/kg Q8W IV dosing.
  • Infliximab: “Patients on Q6W or Q8W IV infliximab can safely switch to Q2W SC infliximab…only patients on Q4W IV infliximab need Q1W SC dosing”
  • Vedolizumab: “Only patients on Q4W IV vedolizumab should switch to Q1W SC dosing”
  • Both agents: “Switching 4 instead of 8 weeks after the last IV dose can hit SS[steady state] faster, thereby avoiding the risk of temporary underexposure.”

My take: It is still important to see how switching from IV to SC route affects clinical outcomes in real-world cohorts. This study, though, does provide a good starting point when trying to provide the right dose frequency to achieve good therapeutic troughs.

Related blog posts:

Japanese Maple tree

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

IBD Updates: SC Vedolizumab, PRODUCE study: Specific Carbohydrate Diet, Racial Epidemiology of IBD, and Microbiome in UC

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Briefly noted –all of these articles are open access:

A Volkers et al. AP&T 2022; https://doi.org/10.1111/apt.17153 Open access: Real-world experience of switching from intravenous to subcutaneous vedolizumab maintenance treatment for inflammatory bowel disease. In this prospective cohort study, patients (n=135) with IBD who had ≥4 months IV vedolizumab were switched to SC vedolizumab. 

Key findings:

  • 4 patients with Crohn’s disease had loss of response.
  • 9% of patients were switched back to IV vedolizumab due to adverse events or fear of needles.
  • Median clinical and biochemical disease activity remained stable after the switch. Median vedolizumab serum concentrations increased from 19 μg/ml at the time of the switch to 31 μg/ml 12 weeks after the switch (p < 0.005).

Related blog posts:

HC Kaplan et al. Am J Gastroenterol 2022 Jun 1;117(6):902-917. Open access: Personalized Research on Diet in Ulcerative Colitis and Crohn’s Disease: A Series of N-of-1 Diet Trials. In this study, 21 patients (completed trial) were randomized to 1 of 2 sequences of 4 alternating 8-week SCD (specific carbohydrate diet) and MSCD (modified specific carbohydrate diet) periods.

Key findings: “SCD and MSCD did not consistently improve symptoms or inflammation.” “Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not.” The authors note that it took 18 months to recruit 54 patients for this study across 19 research sites.

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EL Barnes et al. Inflamm Bowel Dis 2022; 28: 983-987. Open access: Racial and Ethnic Distribution of Inflammatory Bowel Disease in the United States The authors electronic health records from 337 centers from January 2013 to December 2018 with nearly 40 million patients in U.S.

Key findings:

  • Black adult patients were significantly less likely than White patients to have a diagnosis of CD (odds ratio [OR], 0.53) or UC (OR, 0.41). Pediatric Black patients were also less likely to have a diagnosis of CD (OR, 0.41) or UC (OR, 0.38)
  • Adult Hispanic patients were less likely to have a diagnosis of CD (OR, 0.33) or UC (OR, 0.45) compared with non-Hispanic patients. Similarly, pediatric Hispanic patients were less likely to have a diagnosis of CD (OR, 0.34) or UC (OR, 0.50).
  • Thus, these data suggest that CD and UC are modestly less prevalent among patients of non-White races and Hispanic ethnicity

M Frioirksmork et al. Inflamm Bowel Dis 2022; 28: 1081-1089. Open access: Similar Gut Bacterial Composition Between Patients With Ulcerative Colitis and Healthy Controls in a High Incidence Population: A Cross-sectional Study of the Faroe Islands IBD Cohort. This cross-sectional study from the Faroe Islands (which has very high incidence of IBD) consisted of 41 patients with established ulcerative colitis and 144 age- and sex-matched healthy controls.

Key findings: There was a similarity in bacterial community composition and absence of the beneficial Akkermansia genus in both groups.

Pipeline Medications for Ulcerative Colitis (Part 1) & Face Mask Shortages

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Before getting to today’s post, I wanted to provide a link on why we are desperately short of face masks in the midst of this crisis: NY Times: How the World’s Richest Country Ran Out of a 75-Cent Face Mask

An excerpt:

The answer to why we’re running out of protective gear involves a very American set of capitalist pathologies — the rise and inevitable lure of low-cost overseas manufacturing, and a strategic failure, at the national level and in the health care industry, to consider seriously the cascading vulnerabilities that flowed from the incentives to reduce costs…

Given the vast global need for masks — in the United States alone, fighting the coronavirus will consume 3.5 billion face masks, according to an estimate by the Department of Health and Human Services — corporate generosity will fall short. People in the mask business say it will take a few months, at a minimum, to significantly expand production…

Hospitals began to run out of masks for the same reason that supermarkets ran out of toilet paper — because their “just-in-time” supply chains, which call for holding as little inventory as possible to meet demand, are built to optimize efficiency, not resiliency.

My take: Conserve, conserve, conserve PPE -supply chains meeting the need is NOT imminent.

—————

Several articles from Gastroenterology highlight emerging medications for ulcerative colitis (UC).

Two of the studies:

  • WJ Sandborn et al. Gastroenterol 2020; 158: 550-61.
  • WJ Sandborn et al. Gastroenterol 2020; 158: 562-72.

The first study was a phase 2 randomized trial of etrasimod which is an oral selective sphingosine 1-phosphate receptor modulator.  A total of 156 patients were randomized into 3 groups: placebo, 1 mg etrasimod, and 2 mg etrasimod.

Key findings (graphical abstract):

In the second phase 3, double-blind, double-dummy study, Sandborn et al show that, after the initial 2 intravenous doses,  among patients with an initial response subcutaneous vedolizumab (108 mg every 2 weeks) had similar effectiveness to intravenous vedolizumab (300 mg every 8 weeks); both SC and IV vedolizumab resulted in higher clinical remission rates compared to placebo at 52 weeks in the 216 patients: 46.2%, 42.6%, and 14.3% respectively.

Full text link: Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis

Methotrexate Abstract: Subcutaneous vs. Oral Administration

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A recent abstract (Link: Gut doi:10.1136/gutjnl-2014-307964) indicates that there may be some advantages with subcutaneous methotrexate compared with oral administration, especially at the onset of treatment.

Here’s the abstract (thanks to KT Park for sharing this abstract on his twitter feed):

Efficacy of oral methotrexate in paediatric Crohn’s disease: a multicentre propensity score study

Background Oral methotrexate (MTX) administration avoids weekly injections, reduces costs and may improve quality of life of patients with Crohn’s disease (CD), especially children. Routes of administration have never been systematically compared in CD. We aimed to compare effectiveness and safety of orally (PO) versus subcutaneously (SC) administered MTX in paediatric CD.

Methods 226 children with CD treated with oral or subcutaneous MTX were included in a multicentre, retrospective 1-year cohort study (62% boys, mean age 13.8±2.8 years, 88% previous thiopurines). 38 (17%) were initially commenced on oral, 98 (43%) started subcutaneous and switched to oral and 90 (40%) were treated with subcutaneous only. Matching and ‘doubly robust’ weighted regression models were based on the propensity score method, controlling for confounding-by-indication bias. 11/23 pretreatment variables were different between the groups, but the propensity score modelling successfully balanced the treatment groups.

Results 76 children (34%) had sustained steroid-free remission with a difference that did not reach significance between the PO and the SC groups (weighted OR=1.72 (95% CI 0.5 to 5.9); p=0.52). There were no differences in need for treatment escalation (p=0.24), elevated liver enzymes (p=0.59) or nausea (p=0.85). Height velocity was lower in the PO group (p=0.006) and time to remission was delayed in the PO group (p=0.036; Fleming (0, 1) test).

Conclusions In this largest paediatric CD cohort to date, SC administered MTX was superior to PO, but only in some of the outcomes and with a modest effect size. Therefore, it may be reasonable to consider switching children in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth.

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