KP Quinn et la. Inflamm Bowel Dis 2019; 25: 460-71. This is a terrific review of evaluation and management of pouch disorders.
A Armuzzi et al. Inflamm Bowel Dis 2019; 25: 568-79. This prospective cohort study examined infliximab biosimilar in 810 patients (PROSIT cohort). This included 459 patients naive to anti-TNF therapy (group a) , 196 with previous exposure (group b), and 155 who were switched while on original infliximab (group c). At 12 months, patients without a loss of response were 71%, 64%, and 82% respectively in these three groups.
S Coward et al Gastroenterol 2019; 156: 1345-53. This study from Canada used population-based health administrative data from multiple provinces and then applied autoregressive integrated moving average regression to predict prevalence of IBD in 2030. Key point: “In 2018, 267,983 Canadians were estimated to be living with IBD, which was forecasted to increase to 402,853 by 2030.” This is approximately 1% of the population (981 per 100,000).
F Castiglione et al. Aliment Pharm Ther 2019; 49: 1026-39. This observational longitudinal study with 218 patients with Crohn’s disease who completed 2-years of anti-TNF treatment examined transmural healing via ultrasonography (≤3 mm bowel wall thickness). “Transmural healing was associated with a higher rate of steroid-free clinical remission (95.6%), lower rates of hospitalization (8.8%) and need for surgery 0%).” The authors conclude that transmural healing is associated with better long-term clinical outcomes than mucosal healing.
“Magic Fountain” Barcelona
W El-Matary et al. Inflamm Bowel Dis 2019; 25: 150-5. This retrospective study of 667 children with Crohn’s disease who were prospectively enrolled in an inception study found that 85 (12.7%) had fistulizing perianal disease. The mean infliximab (pre-fourth dose) was 12.7 mcg/mL in responders compared with 5.4 mcg/mL in the active disease group. My take: Higher trough levels are desirable in those with fistulizing disease.
LJT Smits et al. Inflamm Bowel Dis 2019; 25: 172-9. In a prospective cohort with 83 patients with IBD (57 with Crohn’s disease) with at least 2 years of followup, 66% of IBD patients continued CT-P13 after switching from Remicade; two patients developed anti-drug antibodies. The absolute numbers suggest no adverse impact of a single switch to the biosimilar product.
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A Tinsley et al. Inflamm Bowel Dis 2019; 25: 369-76. This study documents the increased risk of influenza and increased influenza complications among IBD patients based on a database cohort of 140,480 patients (with and without IBD). The risk of hospitalization was 5.4% in patients with IBD compared with 1.85% in non-IBD patients.
Related blog post: Almost Everybody Needs Flu Shot -IBD Patients at Higher Risk
YY Xu et al. Inflamm Bowel Dis 2019; 25: 261-9. This meta-analysis included 18 nonrandomized controlled trial studies with 1407 patients who received preoperative infliximab and 4589 patients. The authors showed that preoperative infliximab was not associated with any statistically significant differences for the 2 groups for any complications, reoperation, readmission or mortality.
CN Bernstein et al. Inflamm Bowel Dis 2019; 25: 360-8. This study, using population-based administrative health data (Manitoba) found increased burden of psychiatric disorders in IBD: compared with controls the incidence rate ratio for depression was 1.58, for anxiety 1.39, for bipolar disorder 1.82, and for schizophrenia 1.64.
Related blog post: #NASPGHAN17 Psychosocial Problems in Adolescents with IBD
View from Ryan Mountain, Joshua Tree National Park
A recent position paper from ESPGHAN/Porto Group:
Full text: Use of Biosimilars in Pediatric Inflammatory Bowel Disease: An Updated Position Statement of the Pediatric IBD Porto Group of ESPGHAN. L de Riddler et al. JPGN 2019; 68: 144-53
- There are sufficient data (by extrapolation from different indications, adult data and limited pediatric data) to state that in children with IBD who are indicated for IFX treatment, CT-P13 is a safe and efficacious alternative to the originator IFX for
induction, and maintenance, of remission. 97% agreement
- A switch from the originator infliximab to CT-P13 may be considered in children with IBD in clinical remission, following at least 3 induction infusions. 84% agreement
- Multiple switches (>1 switch) between biosimilars and reference drug or various biosimilars are not recommended in children with IBD, as data on interchangeability is limited and traceability of the drugs in case of loss of efficacy and/or safety signals may be compromised. 97% agreement
- Physicians/institutions should keep records of brands and batch numbers of all biological medicines (including biosimilars) administered. 89% agreement
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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. 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.
B Feagan et al. Systematic review: efficacy and safety of switching patients between reference and biosimilar infliximab. Alim Pharm Ther 2019 Jan;49(1):31-40. “While available data have not identified significant risks associated with a single switch between reference and biosimilar infliximab, the studies available currently report on only single switches and were mostly observational studies lacking control arms. Additional data are needed to explore potential switching risks in various populations and scenarios.”
MP Pauly et al. Incidence of Hepatitis B Virus Reactivation and Hepatotoxicity in Patients Receiving Long-term Treatment with Tumor Necrosis Factor Antagonists. Clin Gastroenterol Hepatol 2018; 16: 1964-73. Using data from 8887 adults, this retrospective review found “HBV reactivation iin 39% of patients who were HBsAg+ before therapy, but not in any patients who were HBsAg-negative and anti-HBc+ before therapy.”
D Lauritzen et al. Pediatric Inflammatory Bowel Diseases: Should We Be Looking for Kidney Abnormalities? Inflamm Bowel Dis 2018; 24: 2599-2605. In a cross-sectional cohort of 56 children with IBD, the authors found 25% “had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease.” The authors note that plasma cystatin C is a useful biomarker for glomerular filtration as it less dependent on nutritional status; it is increased in the setteing of a decline in GFR.
L Pouillon et al. Mucosal Healing and Long-term Outcomes of Patients with Inflammatory Bowel Diseases Receiving Clinic-Based vs Trouhg Concentration-Based Dosing of Infliximab. Clin Gastroenterol Hepatol 2018; 16: 1276-83. This retrospective study with patients who completed TAXIT maintenance phase found that patients who received trough-based infliximab dosing had a lower discontinuation rate of infliximab compared with clinic-based dosing (2 of 21 [10%] vs. 10 of 27 [37%]). However, both groups had >75% of patients able to continue infliximab for more than 3 years after the trial.
N Ouldali et al. Early Arthritis Is Associated With Failure of Immunosuppressive Drugs and Severe Pediatric Crohn’s Disease Evolution. Inflamm Bowel Dis 2018; 24: 2423-30. In this retrospective study with 272 patients with Crohn’s disease, 23.9% (n=65) developed arthritis and this was associated with failure of immunosuppressive drugs with OR of 6.9 after 2 years. In this study, immunosuppressive drugs refers to thiopurines and methotrexate. By the completion of study, a much greater proportion of those with arthritis required biologic treatment (76% vs 32%, OR 4.3)
October 31, 2018: FDA Approves Sandoz’s Biosimilar Adalimumab, Hyrimoz
The FDA has approved Sandoz’s biosimilar adalimumab, Hyrimoz (adalimumab-adaz).
The drug has been approved to treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn disease, ulcerative colitis, and plaque psoriasis…
Despite today’s approval, US patients will have to continue to wait for access to Hyrimoz, as the biosimilar will not enter the US market until 2023. Earlier this month, Sandoz announced a global settlement of patent disputes with AbbVie over the drug. While the settlement allowed Sandoz to launch Hyrimoz in the European Union on October 16, 2018, it forestalled US market entry until September 30, 2023.
My take: Why will this biosimilar be allowed in Europe but not U.$?
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Briefly noted: A Meyer et al. Ann Intern Med. 2018. DOI: 10.7326/M18-1512
Abstract link: Effectiveness and Safety of Reference Infliximab and Biosimilar in Crohn Disease: A French Equivalence Study
In this study with 5050 patients, based on review of an administration database, the authors found the following:
- In multivariable analysis of the primary outcome, CT-P13 (biosimilar) was equivalent to infliximab reference product (RP) (HR, 0.92 [95% CI, 0.85 to 0.99]). 1147 patients in the RP group and 952 patients in the CT-P13 group met the composite end point (including 838 and 719 hospitalizations, respectively).
- No differences in safety outcomes were observed between the 2 groups: serious infections (HR, 0.82 [CI, 0.61 to 1.11]), tuberculosis (HR, 1.10 [CI, 0.36 to 3.34]), and solid or hematologic cancer (HR, 0.66 [CI, 0.33 to 1.32]).
The authors conclude that “real-world data indicates that the effectiveness of CT-P13 is equivalent to that of RP for infliximab-naive patients with CD.”
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Briefly noted: N Chanchlani et al. JPGN 2018; 67: 513-9. The authors report on the use of infliximab biosimilar (IFX-B), n=82, compared to infliximab originator (IFX-O) in 175.
- While the authors did not find a difference with the biosimilar in terms of efficacy and adverse effects, this finding is quite limited; only 28 in IFX-O and 19 in IFX-B had a physician global assessment data which was used to determine efficacy.
- The authors noted that less than 20% of their patients had a baseline and 3-month followup PCDAI recorded.
- In addition, of those with available data, less than half (44%) had screening for hepatitis B and tuberculosis.
- The authors estimate that 875,000 pounds would have been saved for a 1-year period with universal adoption of biosimilars
My take: This study, due to incomplete data, does not add much to our knowledge about biosimilars. It does indicate that better screening prior to infusions for HBV and tuberculosis is needed along with more well-documented experience.
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