Briefly noted from Twitter:
Also –with regard to Methotrexate:
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.
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.
Related blog posts:
A recent clinical review (X Roblin et al. Inflamm Bowel Dis 2018; 24: 1904-9) examines the utility of proactive drug monitoring of anti-TNF therapy in inflammatory bowel disease.
The authors note that several observational trials suggested that proactive drug monitoring would help optimize the effect of anti-TNF therapy, especially infliximab. However, two randomized controlled clinical trials, TAXIT (n=273) and TAILORIX (n=122), were not able to show long-term benefit from proactive therapeutic monitoring.
At the same time, the authors note that a recent trial (Ungar B et al. Clin Gastroenterol Hepatol 2016; 14: 550-7, e2) has shown that infliximab trough levels >5 mcg/mL and adalimumab levels >7.2 mcg/mL identified mucosal healing with 85% specificity. Higher cutoffs showed only minimal further increase in mucosal healing rates.
My take: To this point, controlled trials have not shown that proactive drug monitoring of anti-TNF therapy is beneficial; this review explains the design and limitations of these studies. My personal view is that more studies are needed to know if proactive drug monitoring is worthwhile. Proactive drug monitoring may be more useful in children/adolescents than adults due to much greater variation in size and dosing.
A recent commentary on therapeutic drug monitoring (from KT Park Twitter Feed): Therapeutic Targets in IBD
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Vitamin D Receptor Signaling in IBD. Inflamm Bowel Dis 2018; 24: 1149-54. This article reviews the ways vitamin D/vitamin D receptor may contribute to the genetic, environmental, immune, and microbial aspects of IBD.
LY Chi et al. Inflamm Bowel Dis 2018; 24: 1344-51. This study with 223 pediatric patients & young adults found that current or prior combination therapy with infliximab, compared to monotherapy resulted in higher infliximab levels and lower antibody formation. Combination agent was mainly methotrexate (n=71) rather than thiopurine (n=13). In those with infliximab dose <10 mg/kg, those currently receiving combination therapy had median level of 11.1 compared with 7.0 for prior combination and 5.86 for monotherapy (never combination).
CM Johnson et al. Clin Gastroenterol Hepatol 2018; 16: 900-7. In this retrospective study with 1466 patients with Crohn’s disease, the subset of patients with granulomas (n=187, 12.8%) were associated with a more aggressive phenotype and a younger age at diagnosis (23.6 years compared with 27.9 years; P= .0005). These patients had higher rates of steroid use, narcotic use, more stricturing and penetrating disease along with increase rates of surgery.
E Theodoraki et al. Inflamm Bowel Dis 2018; 24: 1266-71. This study with 82 infliximab-treated patients with a mean age of 44 years found elevated CK levels (>180 U/L) in 30.5%, compared with 11% of control group (IBD patients not receiving biologic therapy). The median CK value in the IFX group was 123.5 U/L compared with 81 U/L in the control group (P<0.0001). All patients had at least 3 CK measurements. The authors recommend: “Based on our results, we recommend monitoring CK levels and clinical symptoms of muscle pain and weakness in IBD patients on IFX treatment.”
In the associated commentary (pg 1272-3), the authors note that CK is found in mitochondria, mainly in cardiac muscle, brain, skeletal muscle and other visceral tissues. The 2 subunits may create 3 isoenzymes: CK-MB (myocardium), CK-MM (skeletal muscle), and CK-BB (neurons). CK can be elevated in health and disease but “in the absence of symptoms, usually do not require any further investigations.” In a small number of individuals, elevated CK can be due to macro-CK (macrocretin) due to measurement difficulties with macroenzymes.
My take: This study suggests that elevated CK levels are common in adults receiving IFX and to avoid overreaction.
A recent clinical report (E Barfield et al. JPGN 2018; 66: 680-86) will be influential. This guideline is from the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Congratulations to my partner, Chelly Dykes, who is one of the coauthors.
Full text: Assuring Quality for Non-Hospital Based Biologic Infusions in Pediatric Inflammatory Bowel Disease: A Clinical Report from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
For many years, our office has had an office-based infusion center which has provided infusions in a safe and cost-effective manner. Recently, there have been some situations in which home-based infusions have been proposed either to lower costs and/or for convenience. This report succinctly describes the hurdles that need to be addressed before recommending this treatment pathway. As noted below, patient safety encompasses a great deal more than infusion reactions. Delays in infusions (which can increase risk of loss of response) due to reactions and lapses in communication are additional issues.
Recommendation 1: Home- or office-based infusions should ensure safe administration of the biologic infusion, provide reliable execution of infusion-related orders (eg, laboratories for therapeutic drug monitoring, dose optimization protocols, etc), and be equipped to recognize and respond to potential complications.
Recommendation 2: Pediatric home- or office-based infusions, particularly for patients 12 years and younger, should be staffed by a pediatric nurse professional with Pediatric Advanced Life Support (PALS) certification and clinical experience with pediatric patients.
Recommendation 3: Evidence-based standard of care for biologic therapy maximizing effectiveness and treatment sustainability should be established before initiating home or office-based infusions.
Recommendation 4: Home- or office-based infusion pathways that decrease opportunity loss for patients and families and deliver high-quality, patient-centered care should be supported and reproduced.
Recommendation 5: Pediatric gastroenterologists should ensure appropriate shared liability with IHSAs to deliver high-quality care in home-based infusions for children by executing pragmatic steps as outlined below:
Recommendation 6: A more equitable division of labor should be established to offset increased administrative burden placed on the pediatric gastroenterologist and medical team to effectively facilitate and maintain home- or office-based infusions, especially when driven by payer-mandated policies.
Recommendation 7: …Among patients receiving home- or office-based infusions, unreliable follow-up care with the provider as scheduled is grounds for discontinuation of home- or office-based biologic therapy.
Recommendation 8: A proper appeals process should be in place to prevent cost transference from payer to patient in payer-mandated decisions for home- or office-based infusions.
Our office practice:
My take: In my experience, office-based infusions can be provided safely and in a cost-effective manner. While the convenience of home-based infusion is desirable, before implementing broadly, issues regarding communication, safety protocols, and documentation to allow modifications in therapy need to be proactively addressed. Families may not realize some of the complexities involved in managing infusions and how these issues could affect their child’s long-term response to biologic therapy.
Related blog posts:
The following image relates to another convenience-related health trend:
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.
A recent study (G Fiorino et al. IBD 2018; 24: 601-6, editorial by KH Katsanos et al 465-6) provides more data on “full interchangeability” in regards to infliximab (IFX) and biosimilars CT-P13 and SB2. Full abstract below.
Key finding in study:
Points from the editorial:
Background: Infliximab (IFX) biosimilars CT-P13 and SB2 have comparable efficacy, safety, and immunogenicity to the originator Remicade (RMC). However, concerns about cross-switching patients between the 3 brands were raised in the absence of cross reactivity data between them. We aimed to determine whether antibodies to infliximab (ATI) in inflammatory bowel disease (IBD) patients cross-react with RMC, CT-P13, and SB2.
Methods: Based on previous ATI status, samples from 34 patients participating in the BIOSIM01 study (13 RMC, 9 CT-P13, and 12 switchers) were selected. Patients were treated with either RMC only, or CT-P13 only, or with RMC switched to CT-P13. Additionally, 28 IFX-naïve patients were assayed as controls. In total, 180 samples were analyzed. ATI trough levels were measured in parallel with 3 different bridging Enzyme Linked Immunosorbent Assays constructed using the 3 drugs. Spearman’s coefficient and percentages of agreement were used to study the correlation between each assay.
Results: In total, 76 samples out of 152 IFX-treated patient samples were ATI-positive (30 RMC, 14 CT-P13, and 32 switchers). All resulted ATI-positive when either CT-P13 or SB2 bridging assays were used. The overall percentage of agreement was 100% when compared either with CT-P13 or SB2 assays. No significant differences were found among ATI levels and coefficients (Spearman’s 0.98 to 1.0, P < 0.0001).
Conclusions: ATI of RMC-treated, CT-P13-treated or RMC to CT-P13 switched patients show full cross-reactivity with CT-P13 and SB2. Findings suggest that immunodominant epitopes in the reference and CT-P13 drugs are equally present in SB2. Data support full interchangeability between biosimilars in regard to immunogenicity.
My take: In patients doing well with IFX, switching to a biosimilar is not currently recommended. In patients naive to IFX, use of IFX or biosimilar is expected to have similar efficacy.
Related study: B Kang et al. IBD 2018; 24: 607-16. This prospective study of 36 pediatric patients did not identify any significant differences in efficacy…or immunogenicity after switching from IFX to CT-P13.
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