Real-world Effectiveness Analysis Research Articles

P708 Multiple Biosimilar Infliximab Switching is Not Associated with Adverse Outcomes in Inflammatory Bowel Disease: A Real-World Effectiveness Analysis in a National U.S. Cohort

Abstract Background Infliximab (IFX) biosimilars are available for inflammatory bowel disease (IBD). Many options of IFX biosimilars exist, however there is a paucity of data on the safety and efficacy of switching between multiple IFX biosimilars. The goal of this study is to evaluate the safety and outcomes in patients who received multiple IFX biosimilars in a National U.S. Cohort of patients with IBD. Methods We conducted a retrospective cohort study of IBD patients on maintenance IFX originator from 2017- 2019 in the national Veterans Affairs (VA) healthcare system. Crohn’s disease (CD) and ulcerative colitis (UC) patients were identified using a previously validated algorithm. Cases, exposures and outcomes were confirmed by chart review. Patents on IFX originator were identified by dispensed medication from the VA Corporate Data Warehouse. Patients were classified as no-switch (NS)- receiving originator but no biosimilar during study period, Single Switch (SS)- switch from originator to one biosimilar, or Double Switch (DS)-switch from IFX originator to two different biosimilars. Primary outcome was IBD flare, defined as escalation of steroid, IBD-related Emergency department visit or hospitalization within 12 months. Secondary outcomes were immunogenicity, serious infection, and infusion reaction. Event rates of the DS group were compared to NS and SS groups using univariate and multivariate (MV) logistic regression models adjusting for patient and non-patient factors. Results 789 patients (487 CD, 298 UC) on maintenance IFX originator were identified. Of these, 410 patients were categorized as NS, 249 as SS, and 130 as DS. Overall, the rate of flare within 12 months was 19.9% (22.2% NS, 15.3% SS, 21.5% DS, p= 0.08), rate of infection was 11.2% (11.5% NS, 8% SS, 16.2% DS, p= 0.056). No statistically significant differences in rates of immunogenicity or infusion reaction were identified between the DS and NS or SS groups. In MV logistic regression including age, race, gender, medication, comorbidity and VA priority status, no significant differences in flares at 12 months was observed between DS (ref) and NS (aOR 1.12, 95% CI 0.68-1.84), or SS groups (aOR 0.64, 95% CI 0.36-1.12). In MV analyses, SS was associated with lower rate of infection compared to DS (aOR 0.41, 95% CI 0.21-0.82). Conclusion In a national U.S. cohort of patients with IBD, multiple IFX biosimilar switching was not associated with flare at 12 months compared to patients continued on IFX originator or with a single IFX biosimilar switch. However, DS was associated with increased odds of infection compared to single switch. These findings provide reassurance that multiple IFX biosimilar switching for IBD is effective but further study on infection risks may be warranted.

Real-world effectiveness analysis of oral versus subcutaneous semaglutide in patients with type 2 diabetes mellitus

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

First Real-World Effectiveness Analysis of Preschool Peanut Oral Immunotherapy

To examine the effectiveness and safety of peanut oral immunotherapy (POIT) after 1 year of maintenance in preschool-aged children.In the study, researchers included 161 patients aged 9 to 70 months who successfully completed 1 year of maintenance POIT and were eligible for follow-up oral food challenge (OFC). The inclusion criteria were having a history of objective reaction to peanut and a positive test result (either a skin-prick test [SPT] or peanut-specific immunoglobulin E [ps-IgE]) or at least 1 objective reaction with dosing during build-up, along with a predetermined ps-IgE level and SPT wheal size.Preschoolers enrolled in the study were given gradually increasing peanut protein doses over 16–22 weeks at clinic visits, building up to a maintenance dose of 300 mg. The children then ingested 300 mg of peanut protein daily for a year. After ∼12 months, the participants were invited to participate in a follow-up peanut OFC. SPT and/or ps-IgE were obtained at baseline and selectively throughout the maintenance and follow-up OFC visits. Symptoms of allergic reactions occurring were recorded and graded 1 to 5.Of the patients who received a year of maintenance therapy and underwent follow-up OFC (n = 117), 92 (78.6%) tolerated a cumulative dose of 4000 mg peanut protein without any symptoms, and 115 (98.3%) tolerated at least 1000 mg. The dose tolerated had increased on average by 3969 mg in those with a negative follow-up OFC and by 3376 mg in those with a positive follow-up OFC. SPT wheal size was also significantly decreased after a year regardless of follow-up OFC result; however, the decrease in ps-IgE was not statistically significant. Those with reactions at the follow-up OFC had either grade 1 (14.5% of all who underwent OFC), grade 2 (6%), or grade 3 (0.85%). No one had a grade 4 or 5 reaction. Of the 124 patients with safety outcomes analyzed during maintenance therapy, 111 (89.5%) were symptom-free during POIT dosing, 10 (8.1%) had grade 1 reactions, 3 (2.4%) had grade 2 reactions, and only 2 (1.6%) required epinephrine for POIT dosing reactions.POIT is effective for preschoolers, protecting against at least 1000 mg peanut protein exposure after one year of maintenance therapy in 98.3% of children and allowing consumption of up to 4000 mg in 78.6%. It is also safe during maintenance, with nearly 90% of children symptom-free during maintenance dosing.POIT has emerged as a patient-preference–sensitive option to increase tolerance to peanut protein and protect against accidental exposure. Previous studies have revealed that increasing the peanut threshold to 1000 mg provides 99% protection from accidental exposures, and commercial POIT product is now approved in children 4 to 17 years old. This is the first real-world study revealing that the majority of preschoolers (98.3%) are able to tolerate 1000 mg after a year of POIT maintenance therapy. Mounting evidence suggests POIT may be safer and more effective when initiated at younger ages, likely because of a milder allergic phenotype, less patient aversion, and opportunity for better adherence from close parental supervision. Preschool POIT is a promising disease-modifying intervention that, in the context of shared decision-making with an experienced pediatric allergist, is likely to dramatically improve health and economic outcomes for patients and families.

Pangenotypic direct-acting antiviral agents for mixed genotype hepatitis C infection: A real-world effectiveness analysis.

Pangenotypic direct-acting antiviral agents (DAAs) glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL) are effective against all hepatitis C virus (HCV) genotype infections. However, data on pangenotypic DAA treatment for mixed genotype HCV infection are sparse. This is a retrospective, single site cohort study analyzing all patients with mixed HCV genotype infections treated with GLE/PIB or SOF/VEL from August 2018 to August 2020 in Chiayi Chang Gung Memorial Hospital, Taiwan. The primary study endpoint was sustained virologic response (SVR) 12weeks after treatment cessation. We also reported adverse events (AEs). A total of 108 patients with mixed infections of any two or three genotypes of 1a, 1b, 2, 3, and 6 received pangenotypic DAAs during the study period. A total of 67 patients received GLE/PIB and 41 received SOF/VEL. The evaluable population analysis revealed SVR rates of 94% (63/67) and 95.1% (39/41) for GLE/PIB and SOF/VEL therapy, respectively, and the per-protocol analysis revealed an SVR of 100% for both regimens. Four patients in the GLE/PIB group and two patients in the SOF/VEL were lost to follow-up. The most common AEs for GLE/PIB versus SOF/VEL therapy included pruritus (14.9% vs 2.4%), fatigue (6.0% vs 7.3%), abdominal discomfort (4.5% vs 7.3%), and acid reflux (3.0% vs 4.9%). DAA-related significant laboratory abnormalities occurred in three patients with >1.5×elevated bilirubin level in the GLE/PIB group. None of the above AEs resulted in DAA discontinuation. Pangenotypic DAAs are well tolerated by and yield high SVR rates in patients with mixed genotype HCV infection.

Real-World Effectiveness Analysis of Switching From Liraglutide or Dulaglutide to Semaglutide in Patients With Type2 Diabetes Mellitus: The Retrospective REALISE-DM Study.

IntroductionInjectable semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that was previously shown to be superior to liraglutide and dulaglutide in head-to-head comparisons in GLP-1 RA-naïve individuals. It is hypothesized that semaglutide will cause further reductions in glycated hemoglobin A1c (HbA1c) and weight in type 2 diabetes mellitus (T2DM) patients previously treated with liraglutide or dulaglutide. The REALISE-DM study provides the first real-world evidence of the effectiveness and tolerability of semaglutide in patients switching from another GLP-1 RA.MethodsThis retrospective real-world effectiveness analysis included T2DM adults who were on a stable dose of liraglutide or dulaglutide prior to switching to semaglutide. The primary outcome was change in HbA1c. Secondary outcomes were the changes in weight and body mass index (BMI), the occurrence of gastrointestinal side effects (GSEs), and discontinuations. Linear mixed models were used to estimate changes in HbA1c, weight, and BMI, and logistic regression was employed to analyze GSEs and discontinuations.ResultsSix months after the 164 patients in this study had switched to semaglutide, their mean HbA1c had decreased by 0.65% (7.1 mmol/mol) (95% prediction interval [PI]: 0.48, 0.81% [5.2, 8.9 mmol/mol]) from a baseline of 7.9% (interquartile range [IQR]: 7.3, 8.8) (62.8 mmol/mol [IQR: 56.3, 72.7]), while their weight and BMI had reduced by 1.69 kg (95% PI: 1.01, 2.37) and 0.59 kg/m2 (95% PI: 0.34, 0.84), respectively. Nineteen patients (11.6%) developed GSEs after switching.ConclusionsThis study supports switching T2DM patients on liraglutide or dulaglutide to injectable semaglutide to achieve further reductions in HbA1c and weight. Although a small number of GSEs occurred, semaglutide was well tolerated by the majority of the patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-020-00984-x.

First Real-World Effectiveness Analysis of Preschool Peanut Oral Immunotherapy

We previously described safety of preschool peanut oral immunotherapy (P-OIT) in a real-world setting; 0.4% of patients experienced a severe reaction, and 4.1% received epinephrine, during build-up. To determine the effectiveness of preschool P-OIT after 1 year of maintenance. Preschoolers (9-70 months) with at least 1 objective reaction to peanut (during baseline oral food challenge (OFC) or P-OIT build-up) received a follow-up OFC to cumulative 4000 mg protein after 1 year on 300 mg peanut daily maintenance. Effectiveness of desensitization was defined as proportion of patients with a negative follow-up OFC. Symptoms and treatment at follow-up OFC were recorded. Of the 117 patients who successfully completed 1 year of P-OIT and subsequently underwent a cumulative 4000-mg follow-up OFC, 92 (78.6%) had a negative OFC and 115 (98.3%) tolerated a cumulative dose of greater than or equal to 1000 mg. For the 25 (21.4%) who reacted, their threshold increased by 3376 mg (95% CI, 2884-3868) from baseline to follow-up; 17 (14.5%) patients experienced grade 1 reactions, 7 (6.00%) grade 2, and 1 (0.85%) grade 3. Two patients (1.71%) received epinephrine associated with P-OIT, and 1 (0.85%) went to the emergency department. Our data demonstrate that real-world preschool P-OIT is effective after 1 year of maintenance for those who received a follow-up OFC. For those who reacted, their threshold increased sufficiently to protect against accidental exposures. P-OIT should be considered for preschoolers as an alternative to current recommendations to avoid peanut.

First Real-World Effectiveness Analysis of Preschool Peanut Oral Immunotherapy

We previously described safety for 270 preschoolers receiving peanut oral immunotherapy (P-OIT) in a real-world setting; 0.4% of patients experienced a severe reaction, and 4.1% received epinephrine, during build-up. This study describes effectiveness of P-OIT. Preschoolers (9-71 months) with a baseline reaction to peanut (during baseline oral food challenge (OFC) or build-up), received an OFC to 4,000mg protein after ∼1 year of ingesting ∼300mg peanut protein daily maintenance. Effectiveness was defined as percentage of patients with a baseline reaction who passed the 1-year OFC. For those who reacted at the 1-year OFC, median cumulative dose (CD) for baseline reaction, 1-year OFC, and change from baseline to 1-year OFC, were calculated. Between 2017 -2019, 87 patients had a baseline reaction and a 1-year OFC, of which 68 passed the 1-year OFC (effectiveness=78.1%). For the 19 (21.9%) who reacted at the 1-year OFC, median CD for the baseline reaction was 12mg (Interquartile range, IQR: 10, 75); 4,000mg (IQR: 4000, 4000) for the 1-year OFC, and 3988mg (IQR: 3920, 3995) for the change from baseline to 1-year. Our data demonstrate that real-world preschool P-OIT is highly effective after 1 year of maintenance. For the minority who reacted at the 1-year OFC, their threshold increased dramatically. A limitation of our data is more children reached 1-year maintenance than the number offered a 1-year OFC. Our data suggest that P-OIT has a higher effectiveness in preschoolers compared to reported efficacy in older children. We predict greater effectiveness in preschoolers with longer duration of maintenance.

Which Should be Pursued, Cumulative Dose or Dose Intensity: A Real-World Effectiveness Analysis of Bortezomib-Based First Line Treatment for Untreated Multiple Myeloma Patients

Background: The higher cumulative dose of bortezomib associated with better OS was demonstrated by some prospective studies of bortezomib continuing therapy. A cutoff of cumulative bortezomib dose of 39mg/m2 was found in the treatment of multiple myeloma (MM) with VISTA trial recently. However, dose reduction due to adverse events was common. Moreover, many Chinese patients accepted bortezomib injections at a fixed dose of 1.75mg, the half volume of a vial because of economic problems. To clarify if a reasonable cumulative bortezomib dose achieved by prolonged treatment duration with reduced dose intensity can do the same work, we conducted a multicenter retrospective analysis in previously untreated MM patients with the initial treatment of bortezomib-based regimens.Method: From March 2005 to December 2014, 579 previously untreated MM patients received the bortezomib-based chemotherapy with informed consents in three hematologic centers of Beijing. Median age at the diagnosis was 59 years (range: 27~89). Initial chemotherapeutic regimens included BD, PAD, BCD and VMP. After median of 4 cycles (range: 0.25~13.00) of treatment, the median cumulative dose of bortezomib was 28mg (range: 1.75~124.80). The median follow-up of surviving patients was 26.0 months (2.0-123.0). Seventy nine patients recieved autologous hematopoietic cell transplantation (ASCT) according to the eligibility and patients' desire.Results: To overcome confounding effects of early discontinuations/deaths on the cumulative dose, a landmark analysis was conducted at 6 months, eliminating patients who died before this time from the analysis. Among the patients survived the initial 6-month treatment, 450 treated with chemotherapy alone and 78 received ASCT.ROC analysis showed the cumulative bortezomib dose predicted survival in chemotherapy group with the AUC of 0.617 (95%CI: 0.565~0.670, P<0.001). A cutoff value of cumulative bortezomib dose was 20.75mg with optimal sensitivity and specificity of 0.831 and 0.373, respectively. The patients' characteristics of both low (<20.75mg) and high (≥20.75mg) cumulative bortezomib dose groups were comparative. The high cumulative dose group had superior OS than the low cumulative dose group (median OS: 51.0 months (95%CI: 44.66-57.34) vs. 42.0 months (95%CI: 33.24-50.76), P=0.015). However, PFS was not significantly different between the two groups (P=0.994). Two hundred and forty eight (65.3%) patients initiated treatment of bortezomib with the fixed dose of 1.75mg, and 202 (34.7%) patients had the standard dose of 1.3 mg/m2. Bortezomib dose reduction occured in 50 patients. Twenty nine (11.7%) patients of the standard dose intensity group and 2(1.0%) of the fixed dose intensity group had the dose reduction due to adverse events. And the other 19 patients reduced bortezomib dose for other reasons. PFS and OS of the patients with reduced dose intensity were not significantly different from the patients with the standard dose intensity of 1.3 mg/m2 (P=0.183 and 0.482, respectively). However, in the patients with the cumulative bortezomib dose of ≥20.75mg and the standard dose intensity of 1.3mg/m2 was associated with superior survival (P=0.05). Median OS of these patients was 57.0 months (95%CI: 50.62-63.38), while median OS of other patients treated with the cumulative bortezomib dose of <20.75mg or reduced dose intensity was 45.0 months (95%CI: 41.45-48.55). In the ASCT group, we could not find any association between bortezomib dose and the survival.Conclusion: For previously untreated MM patients intend to be treated with chemotherapy alone, we suppose cumulative bortezomib dose ≥20.75mg in the first line treatment should be administered for better OS. Despite reasonable cumulative bortezomib dose, any reduction of the dose intensity from 1.3mg/m2 is associated with inferior OS. For patients treated with ASCT, the association between the bortezomib dose and the survival needs to be elucidated with a long term follow-up. DisclosuresNo relevant conflicts of interest to declare.