Chen C, Hartzema AG, Xiao H, Wei YJ, Chaudhry N, Ewelukwa O, Glover SC, Zimmermann EM. Real-world Pattern of Biologic Use in Patients With Inflammatory Bowel Disease: Treatment Persistence, Switching, and Importance of Concurrent Immunosuppressive Therapy. Inflamm Bowel Dis. 2019 Jul 17;25(8):1417-1427.  


Abstract
BACKGROUND AND AIMS:
Medication persistence, defined as the time from drug initiation to discontinuation of therapy, has been suggested as a proxy for real-world therapeutic benefit and safety. This study seeks to compare the persistence of biologic drugs among patients with inflammatory bowel disease (IBD).

METHODS:
Patients with newly diagnosed IBD were included in a retrospective study using Truven MarketScan database. Treatment persistence and switching was compared among biologic medications including infliximab, adalimumab, certolizumab, golimumab, and vedolizumab. Predictors for discontinuation and switching were evaluated using time-dependent proportional hazard regression.

RESULTS:
In total, 5612 patients with Crohn's disease (CD) and 3533 patients with ulcerative colitis (UC) were included in this analysis. Less than half of the patients continued using their initial biologic treatment after 1 year (48.48% in CD cohort; 44.78% in UC cohort). In the first year, adalimumab had the highest persistence and lowest switching rates for both CD (median survival time: 1.04 years) and UC (median survival time: 0.84 years). In subsequent years, infliximab users were more likely to persist in the use of biologic. Combination therapy with immunomodulators significantly decreased the risk of discontinuation, especially when immunomodulator therapy was started more than 30 days before the biologic (hazard ratio [HR], 0.22; CI, 0.16, 0.32). The major predictors for noncompliance included infection and hospitalization.

CONCLUSION:
Overall, the persistence profiles of biologics suggest a high rate of dissatisfaction or adverse disease outcomes resulting in discontinuation and switching to a different agent. Early initiation of immunomodulators will substantially increase the persistence of biologic treatment.

Published here:

Therap Adv Gastroenterol. 2019; 12: 1756284819853208.

Abstract
Inflammatory bowel disease (IBD) is a spectrum of immune-mediated inflammatory disorders with a complex multifactorial pathogenesis, where different pathways may predominate in different individuals. This complexity will most likely require a panoply of drugs targeting different pathways if one wants to treat to steroid-free sustained remission and mucosal healing. Presently, the mainstay of medical management of IBD is based on 5-aminosalicylates, corticosteroids, thiopurines, methotrexate, antitumor necrosis factor, anti-alpha4 beta7 (α4β7) integrin and anti-interleukin (IL)-12/IL-23 therapies. The discovery of new pathways involved in the pathogenesis of IBD resulted in new drugs targeting Janus kinase/signal transducers and activators of transcription, IL-6, spingosine-1-phosphate, and phosphodiesterase 4, among others. These new therapies might result in more advantageous safety profiles. Several of these new drugs have already been successfully tested in other inflammatory disorders, such as psoriasis or rheumatoid arthritis. In this review, evidence from phase II and phase III randomized controlled clinical trials in patients with IBD involving new biologicals and small molecules are summarized.

​https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537282/

The following study was published in The Lancet

Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn's disease: an international, randomised, double-blind, phase 3 non-inferiority study

Published: March 28, 2019
​DOI: https://doi.org/10.1016/S0140-6736(18)32196-2

Abstract
Objective Evaluate the cost-effectiveness of laparoscopic ileocaecal resection compared with infliximab in patients with ileocaecal Crohn’s disease failing conventional therapy.

Design A multicentre randomised controlled trial was performed in 29 centres in The Netherlands and the UK. Adult patients with Crohn’s disease of the terminal ileum who failed >3 months of conventional immunomodulators or steroids without signs of critical strictures were randomised to laparoscopic ileocaecal resection or infliximab. Outcome measures included quality-adjusted life-years (QALYs) based on the EuroQol (EQ) 5D-3L Questionnaire and the Inflammatory Bowel Disease Questionnaire (IBDQ). Costs were measured from a societal perspective. Analyses were performed according to the intention-to-treat principle. Missing cost and effect data were imputed using multiple imputation. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated to show uncertainty.

Results In total, 143 patients were randomised. Mean Crohn’s disease total direct healthcare costs per patient at 1 year were lower in the resection group compared with the infliximab group (mean difference €−8931; 95% CI €−12 087 to €−5097). Total societal costs in the resection group were lower than in the infliximab group, however not statistically significant (mean difference €−5729, 95% CI €−10 606 to €172). The probability of resection being cost-effective compared with infliximab was 0.96 at a willingness to pay (WTP) of €0 per QALY gained and per point improvement in IBDQ Score. This probability increased to 0.98 at a WTP of €20 000/QALY gained and 0.99 at a WTP of €500/point of improvement in IBDQ Score.

Conclusion Laparoscopic ileocaecal resection is a cost-effective treatment option compared with infliximab.


de Groof EJ, Stevens TW, Eshuis EJ, et al Cost-effectiveness of laparoscopic ileocaecal resection versus infliximab treatment of terminal ileitis in Crohn’s disease: the LIR!C Trial Gut Published Online First: 01 February 2019. doi: 10.1136/gutjnl-2018-317539

BACKGROUND & AIMS:
There is evidence that it is safe and effective for patients with inflammatory bowel diseases (IBD) to switch from maintenance therapy with an original infliximab drug to a biosimilar, but little is known about outcomes of reverse switches and/or multiple switches. We aimed to evaluate the effects of a reverse switch (from a biosimilar to Remicade) in a real-life cohort.

METHODS:
We performed a prospective observational study of 174 unselected and consecutive patients with IBD (136 with Crohn's disease [CD] and 38 with ulcerative colitis [UC]) who received maintenance therapy with the biosimilar in Hungary. In September 2017, patients were switched from the biosimilar (CT-P13) to Remicade, due to reimbursement policies. In our cohort, 8% (n=14) patients had been previously exposed to the originator Remicade. We collected clinical and biochemical information from patients at baseline (time of the switch) and 16 and 24 weeks thereafter. Clinical remission was defined as a Crohn's disease activity index <150 points or no fistula drainage, or a partial Mayo score <3 points for patients with UC. Serum drug trough levels and anti-drug antibodies were measured at baseline and week 16.

RESULTS:
There was no significant difference in the proportion of patients in clinical remission at week 8 before the switch (82.5% with CD and 82.9% with UC), at baseline (80.6% with CD and 81.6% with UC), at week 16 (77.5% with CD and 83.7% with UC), or at week 24 (CD 76.3% with CD and 84.9% with UC) (P=.60 among groups for patients with CD and P=.98 among groups for patients with UC). For all patients, mean serum trough levels of infliximab were 5.33±4.70 μg/ml at baseline and 5.69±4.94 μg/ml at week 16 (P=.71); we did not find significant differences in prevalence of anti-drug antibody at baseline (16.2%) compared with week 16 (16.9%) (P=.87). Four infusion reactions occurred, until week 24 of follow up. There was no difference in outcomes or trough or antidrug antibody levels between patients with or without previous exposure to Remicade.

CONCLUSIONS:
We collected data from a real-life cohort of patients with CD or UC who were switched from maintenance therapy with a biosimilar to Remicade or were treated with only Remicade. No significant changes were observed in remission, trough levels, or antidrug antibodies in patients switched from the biosimilar to Remicade. No new safety signals were detected.


Ilias A, Szanto K, Gonczi L, Kurti Z, Golovics PA, Farkas K, Schafer E, Szepes Z, Szalay B, Vincze A, Szamosi T, Molnar T, Lakatos PL. Outcomes of Patients With Inflammatory Bowel Diseases Switched from Maintenance Therapy with a Biosimilar to Remicade. Clin Gastroenterol Hepatol. 2019 Jan 7.
​

Studies of microbial signatures have improved our understanding of the role of dysbiosis in gut microbiota for the pathogenesis of inflammatory bowel disease (IBD). New technological advances such as next-generation sequencing facilitate investigations on large patient cohorts, but require methodological considerations regarding study design, sample processing, data analysis, and integration. Here, we summarize recent study approaches in microbial ecology with respect to IBD research and discuss crucial process steps for the production and integration of adequate data sets.


Learn more about microbial signatures in this article titled, "Microbial Signatures as a Predictive Tool in IBD—Pearls and Pitfalls."

Since 1999, the Crohn’s Therapy, Resource, Evaluation, and Assessment Tool (TREAT™; ClinicalTrials.gov NCT00553176) Registry has been evaluating the long-term safety outcomes of infliximab and standard-of-care treatment regimens used in the management of Crohn’s disease.  This observational registry was discontinued in May 2012 and data collection continued until final database closure in September 2012.

Lichtenstein GR, Feagan BG, Cohen RD, Salzberg BA, Safdi M, Popp JW Jr, Langholff W, Sandborn WJ. Infliximab for Crohn's Disease: More Than 13 Years of Real-world Experience. Inflamm Bowel Dis. 2018 Feb 15;24(3):490-501. doi: 10.1093/ibd/izx072. PubMed PMID: 29462395.

A new tool called "IBD&me" is now available online, thanks to researchers at Cedars-Sinai Medical Center, a leading IBD research center. The tool explains IBD and biologics and utilizes a decision tree to show different medication profiles. 

Visit: https://ibdandme.org
​

The American Medical Association, American Hospital Association, America's Health Insurance Plans, American Pharmacists Association, Blue Cross Blue Shield Association, and Medical Group Management Association recently issued a consensus statement on improving the prior authorization process.

You can read that statement here:
https://www.ama-assn.org/sites/default/files/media-browser/public/arc-public/prior-authorization-consensus-statement.pdf

Piester T, Frymoyer A, Christofferson M, Yu H, Bass D, Park KT. A Mobile Infliximab Dosing Calculator for Therapy Optimization in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2018 Jan 18;24(2):227-234. doi: 10.1093/ibd/izx037. 
PubMed PMID: 29361094.

BACKGROUND:
Inadequate infliximab (IFX) drug exposure remains a clinical challenge and leads to high loss of response rates and therapy failure in inflammatory bowel disease (IBD). We aimed to determine the feasibility and pilot effectiveness of a novel, web-based, mobile IFX dosing calculator (mIDC) for therapy optimization.

METHODS:
We developed an mIDC leveraging the known clinical variables of C-reative protein (CRP), albumin, patient's weight, disease activity indices, calprotectin, drug trough levels, and antibodies to IFX that significantly affect pharmacokinetics and/or outcomes. A prospective observational cohort study in pediatric and young adult IBD patients receiving maintenance IFX was performed. System-wide practice adoption of mIDC was achieved through a quality improvement (QI) initiative within a hospital-based infusion unit.

RESULTS:
Forty-nine patients (median age: 16.0 years; 55% female; 65% Crohn's disease) were followed over 9 months. mIDC recommendations for dose optimization were followed by the treating physicians in 198 (89%) out of 222 infusions. Twenty-eight (13%) of 222 mIDC recommendations were to escalate IFX dosing; 15 (54%) of 28 escalation recommendations were declined, and these patients were more likely to already be receiving IFX dose intensification compared with those in whom escalation recommendations were followed (P < 0.05). From mIDC initiation to end of follow-up, mean albumin levels remained unchanged at 3.8 g/dL. Median CRP remained unchanged at 2 g/L. Median calprotectin levels showed a downward trend from 30 to 27 μg/g (n = 9, P < 0.05). The percentage of patients undergoing therapeutic drug monitoring in clinical care increased from 34% to 86% with the QI initiative. The target median IFX trough goal of >5 μg/mL was achieved with 81% probability throughout the QI initiative, an increase of 12% compared with pre-QI values.

CONCLUSIONS:
The use of a novel mIDC is feasible and potentially effective, facilitating both standardization and individualization of therapy in clinical care. mIDC appears to be a practical IFX dosing tool for point-of-care use, leveraging individual pharmacokinetic considerations.