To the Editor; A Commentary on "Switching From Originator to Biosimilar Human Growth Hormone Using a Dialogue Teamwork: Single-Center Experience From Sweden".
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ABSTRACT:
SUBMITTER: Ekelund M
PROVIDER: S-EPMC4254870 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAs the patents of originator biologics are expiring, biosimilar versions are becoming available for the treatment of inflammatory bowel disease (IBD). However, published switch studies of the first infliximab biosimilar, CT-P13, have delivered ambiguous results that could be interpreted as showing a trend towards inferior effectiveness in Crohn's disease (CD) compared with ulcerative colitis (UC). The aim of this study was to investigate the effectiveness and safety of switching IBD patients from treatment with Remicade to CT-P13.MethodsIn this prospective observational cohort study, all adult IBD patients on Remicade treatment, at four hospitals, were switched to CT-P13. The primary endpoint was change in clinical disease activity at 2, 6, and 12 months after the switch. Secondary endpoints were subgroup analyses of patients with and without concomitant immunomodulators; changes in biomarkers, quality of life, drug trough levels and anti-drug antibodies (ADAbs); and adverse events.ResultsA total of 313 IBD patients were switched (195 CD; 118 UC). There were no significant changes in clinical disease activity, quality of life, biomarkers (except a small but significant increase in albumin in CD) including F-calprotectin, drug trough levels, or proportion of patients in remission. Disease worsening rates were 14.0% for CD and 13.8% for UC; and 2.7% developed ADAbs and 2.2% developed serious adverse events.ConclusionsThis is the largest study of switched IBD patients published to date, and it demonstrates that switching from Remicade to CT-P13 may be done with preserved therapeutic effectiveness and safety in both CD and UC.
| S-EPMC6187418 | biostudies-literature
Project description:BackgroundCurrent literature still lacks studies evaluating the effectiveness and safety of switching from Infliximab originator to SB2 biosimilar in Inflammatory Bowel Diseases (IBDs). We aimed to verify the ability of SB2 to maintain the clinical and biochemical response induced by originator after switching. As secondary outcome, we aimed to verify safety, tolerability and immunogenicity of SB2 biosimilar compared with its IFX originator.MethodsWe prospectively enrolled all patients who switched from originator to SB2 at three Italian IBD Units from August 2018 to April 2020. We collected clinical and biochemical data at the time of switch (T0), and at the first (T1) and the second (T2) visits after switching (mean time from switching: 135 and 329 days, respectively). In addition, data regarding therapeutic drug monitoring at T0 and T1 were recorded.ResultsEighty-five IBD patients (28 with Ulcerative Colitis and 57 with Crohn's Disease) were included in the study. At T1, we observed statistically significant modifications in clinical activity of disease (70 patients were in clinical remission at baseline and 60 at T1 p = 0.02), but not at T2 (p = 0.3). Fecal calprotectin values were not different both at T1 and T2 (both p = 0.9) as well as the rate of concomitant treatment with steroids (p = 0.2 and p = 0.1) or immunosuppressants (p = 0.1 and p = 1.0). Moreover, the need for therapeutic optimization from T0 to T1 and from T1 to T2 was found significant (both p = 0.01). No anti-drug antibodies were identified at T1, and no serious adverse events were recorded.ConclusionsOverall, our data show that most of the patients switching from Infliximab originator to SB2 maintain the clinical and biochemical remission for at least 1 year. Further data are necessary to understand the clinical implications of these findings in the long term.
| S-EPMC8239954 | biostudies-literature
Project description:IntroductionTo save costs to the healthcare system, forced non-medical switch (NMS) policies that cut drug coverage for originator biologics and fund only less expensive biosimilars are being implemented. However, costs related to the impact of NMS on healthcare resource utilization (HCRU) must also be considered. This study aims to summarize the evidence on the economic impact of an originator-to-biosimilar NMS.MethodsA systematic literature review (SLR) was conducted. Publications reporting on HCRU or costs associated with originator-to-biosimilar NMS in the real-world setting were searched in MEDLINE and EMBASE from January 2008 to February 2020. In addition to hand searching the reference lists of relevant publications and SLRs, key conference websites, PubMed, and various government sites were also searched for the 2 years preceding the search (2018-2020).ResultsA total of 1845 citations were identified, of which 49 were retained for data extraction. Most studies reporting on the HCRU associated with NMS reported on post-NMS HCRU alone without a comparison pre-NMS. However, four studies described a difference in HCRU (i.e., investigations pre- vs post-switch or between non-switchers vs switchers), all of which reported a relative increase in HCRU, including laboratory testing, imaging, medical visits, and hospitalizations, amongst patients who underwent an originator-to-biosimilar NMS. Most studies reporting on the costs associated with NMS reported significant savings following NMS on the basis of drug costs alone. However, four studies specifically reporting on the difference of costs following originator-to-biosimilar NMS all demonstrated an increase in HCRU-related costs associated with NMS (increase in HCRU-related costs of 4-37% or 148-2234 2020 Canadian dollars).ConclusionAmongst the studies that reported on the difference in HCRU pre- vs post-switch or between non-switchers and switchers, all showed an increase in HCRU and related costs associated with NMS, suggesting that the expected overall savings due to less costly drug prices may be reduced as a result of an increase in HCRU and its associated costs post-switch. Nevertheless, more real-world studies that include NMS-related healthcare costs in addition to drug costs are needed.
| S-EPMC8799532 | biostudies-literature
Project description:AimsMedical and non-medical switching strategies have been adopted in Europe in the last few years. We aimed to investigate persistence on treatment with a SB5 Adalimumab (SB5) biosimilar after switching from Adalimumab (ADA) originator among patients with inflammatory rheumatic musculoskeletal diseases (iRMD), identifying possible predictors of drug interruption and describing adverse events.MethodiRMD patients previously switched to SB5 after at least 6 months of ADA were enrolled. Data on concomitant medications, disease flares, and persistence on SB5 up to the last available follow up were collected retrospectively. Kaplan-Meier and Cox regression models were used.ResultA total of 172 patients (106 females, ADA duration 5.8 ± 3.8 years) were enrolled, including 34 rheumatoid arthritis, 59 psoriatic arthritis, and 61 axial spondyloarthritis patients. In a 10 ± 3 months follow up, 65 (37.8%) patients presented with adverse events, with 46 (26.7%) showing a clinically defined disease flare (no disease activity and patient reported outcomes assessment were available); 24 patients interrupted SB5 permanently (among them, 11 back-switched to ADA and 8 were prescribed a different biological therapy). Probability of persistence on SB5 was 94.7% at 6 months and 85.1% at 12 months. Baseline corticosteroid [hazard ratio (HR) 3.209, 95% confidence interval (CI) 1.193-8.635, p = 0.021] and therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) (HR 2.876, 95% CI 1.229-6.727, p = 0.015), as well as the baseline corticosteroid dose (HR 1.200, 95%CI 1.026-1.403, p = 0.022) were predictors of drug interruption.ConclusionOur data on persistence of treatment and adverse events are in line with previous reports. Further large cohort studies may confirm baseline corticosteroid and NSAIDs use as predictors of SB5 interruption, helping to identify patients at higher risk of failure after switching.
| S-EPMC8804457 | biostudies-literature
Project description:BackgroundIn 2019, British Columbia's public drug plan, PharmaCare, was the first in Canada to implement a nonmedical switching policy from originator infliximab to its biosimilar, for patients with inflammatory arthritis or psoriasis. We aimed to detect signals of impact on health services utilization during the first year of policy implementation and to provide early data to policy-makers.MethodsWe constructed cohorts of users of originator infliximab: 3 historical cohorts (2016-2018) and 1 policy cohort (2019). We extracted data from BC Ministry of Health databases from 2015 to 2020, as we followed each cohort for 365 days from May 27 of each cohort's respective year. We excluded patients with gastrointestinal conditions and those not covered by PharmaCare. We examined the cumulative incidence of infliximab prescription refills, switching to other biologic drugs and use of additional health services. A log-likelihood ratio of 1.96 compared with the null hypothesis was used as the threshold for differences between the policy cohort and the historical cohorts.ResultsThe study included a total of 572 unique patients: 520 in the 2016 historical cohort, 461 in the 2017 historical cohort, 423 in the 2018 historical cohort and 377 in the policy cohort (with some patients included in multiple cohorts; 335 [58.6%] were included in all 4 cohorts). During months 8 and 9 of follow-up, a transient signal was observed in infliximab refills (7.2% decrease in refilling infliximab for the fourth time for the policy cohort, log-likelihood ratio > 1.96). An anticipated increase in visits to specialists was observed from month 4 forward (15.0%, log-likelihood ratio > 1.96). No signal was observed for increased use of other health services (log-likelihood ratio < 1.96).InterpretationEarly monitoring did not detect signals of negative impacts on health services use during the first year of the policy. Detailed, longer-term cohort studies and hypothesis-testing methods could provide additional assurance about the safety of the policy.
| S-EPMC9259384 | biostudies-literature
Project description:Background: This study investigated the effectiveness and safety of switching from Basalin® to Lantus® in Chinese patients with diabetes mellitus (DM). Methods: A retrospective chart review conducted using the electronic medical records of patients hospitalized at the Qingdao Endocrine and Diabetes Hospital from 2005 to 2016. All patients were diagnosed with DM and underwent switching of insulin from Basalin to Lantus during hospitalization. Data collected included fasting (FBG), pre- and post-prandial whole blood glucose, insulin dose, reasons for insulin switching and hypoglycemia. Four study time points were defined as: hospital admission, Basalin initiation, insulin switching (date of final dose of Basalin), and hospital discharge. Blood glucose measurements were imputed as the values recorded closest to the dates of these four time points for each patient. Results: Data from 73 patients (70 patients with type 2 diabetes, 2 with type 1, and 1 undisclosed) were analyzed. At admission, mean glycated hemoglobin (HbA1c) and FBG were 8.9% (SD=1.75) and 9.98 (3.22) mmol/L, respectively. Between Basalin initiation and insulin switch, mean FBG decreased from 9.68 mmol/L to 8.03 mmol/L (p<0.0001), over a mean 10.8 (SD=6.85) days of Basalin treatment, and reduced further to 7.30 mmol/L at discharge (p=0.0116) following a mean 6.6 (7.36) days of Lantus. The final doses of Basalin and Lantus were similar (0.23 vs. 0.24 IU/kg/day; p=0.2409). Furthermore, reductions in pre- and post-prandial blood glucose were also observed between Basalin initiation, insulin switch and hospital discharge. The incidence of confirmed hypoglycemia was low during Basalin (2 [2.4%]) and Lantus (1 [1.2%]) treatment, with no cases of severe hypoglycemia. Conclusion: In this study population, switching from Basalin to Lantus was associated with further reductions in blood glucose, although the dose of insulin glargine did not increase. Further studies are required to verify these findings and determine the reason for this phenomenon.
| S-EPMC5941245 | biostudies-literature
Project description:IntroductionReal-world data on the comparative effectiveness and safety of switching among different epoetins (including originators and biosimilars) are limited. In light of current debate about interchangeability, prescribers, some patient groups and decision makers are calling for additional post-marketing evidence on the clinical effects of switching between originator and biosimilar epoetins in chronic kidney disease (CKD) patients.ObjectiveThe objective of this study was to evaluate the effectiveness and safety of switching versus non-switching and of switching from originator/biosimilar epoetin alpha (ESA ?) to any other epoetin in CKD patients.MethodsAn observational, record-linkage, multi-database, retrospective cohort study was carried out in four Italian geographical areas. All subjects with at least one ESA ? dispensing between 1 January 2009 and 31 December 2015 were retrieved. Switching was defined as any transition between originator/biosimilar ESA ? to any other epoetin in a series of two consecutive prescriptions up to 2 years. Switchers were matched 1:1 with non-switchers by baseline propensity score and by duration of ESA ? treatment. Switchers and non-switchers were followed up from switching date to a maximum of 1 year. Lack of effectiveness and safety of switching versus non-switching were evaluated through Cox regression models (hazard ratio [HR], 95% confidence interval [CI]). A direct comparison between the two switcher categories (switchers from originator/biosimilar ESA ? to any other epoetin) was also performed.ResultsOverall, 14,400 incident users of ESA ? for anaemia due to CKD (61.4% originator, 38.6% biosimilar) were available for analysis. During the follow-up, we found no differences on effectiveness (HR 1.02, 95% CI 0.79-1.31 originators; HR 1.16, 95% CI 0.75-1.79 biosimilars) and safety outcomes (HR 1.08, 95% CI 0.77-1.50 originators; HR 1.20, 95% CI 0.66-2.21 biosimilars) between switchers and non-switchers of ESA ?. Cumulative probabilities of recording an adverse event, either in terms of lack of effectiveness or safety issue, were the same for two switching categories CONCLUSIONS: In this large-scale Italian observational multi-database study, switching versus non-switching as well as switching from biosimilar/originator ESA ? to any other epoetin in CKD patients is not associated with any effectiveness and safety outcomes.
| S-EPMC6858470 | biostudies-literature
Project description:Background and objectivesThe 52-week, randomized, double-blind, noninferiority, government-funded NOR-SWITCH trial demonstrated that switching from infliximab originator to less expensive biosimilar CT-P13 was not inferior to continued treatment with infliximab originator. The NOR-SWITCH extension trial aimed to assess efficacy, safety and immunogenicity in patients on CT-P13 throughout the 78-week study period (maintenance group) versus patients switched to CT-P13 at week 52 (switch group). The primary outcome was disease worsening during follow-up based on disease-specific composite measures.MethodsPatients were recruited from 24 Norwegian hospitals, 380 of 438 patients who completed the main study: 197 in the maintenance group and 183 in the switch group. In the full analysis set, 127 (33%) had Crohn's disease, 80 (21%) ulcerative colitis, 67 (18%) spondyloarthritis, 55 (15%) rheumatoid arthritis, 20 (5%) psoriatic arthritis and 31 (8%) chronic plaque psoriasis.ResultsBaseline characteristics were similar in the two groups at the time of switching (week 52). Disease worsening occurred in 32 (16.8%) patients in the maintenance group vs. 20 (11.6%) in the switch group (per-protocol set). Adjusted risk difference was 5.9% (95% CI -1.1 to 12.9). Frequency of adverse events, anti-drug antibodies, changes in generic disease variables and disease-specific composite measures were comparable between arms. The study was inadequately powered to detect noninferiority within individual diseases.ConclusionThe NOR-SWITCH extension showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious.
| S-EPMC6850326 | biostudies-literature
Project description:Over time, clinicians have become increasingly comfortable embracing the prescription of biosimilars-highly similar versions of innovator or reference biological agents-for their patients with inflammatory diseases. Although a switch from a reference product to a licensed biosimilar version (or vice versa) is a medical decision robustly supported by the stepwise accumulation of clinical trial evidence concerning comparable safety, immunogenicity, and efficacy between these products, a switch from one biosimilar to another biosimilar of the same reference product, or a cross-switch, is not. Similarity among biosimilars of a reference product is not a regulatory agency concern and therefore is unlikely to be investigated in randomized controlled trials in the foreseeable future. Yet in clinical practice, across a diverse range of patients, the option to cross-switch from one biosimilar to another can and does arise for valid reasons such as convenience or tolerability issues, or driven by third parties (e.g., payers). In the absence of clinical trial data, clinicians must attempt to objectively evaluate the emerging real-world cross-switching evidence within the context of what is known about the science underpinning a designation of biosimilar. That knowledge then needs to be integrated with what clinicians know about their patients and their disease on a case-by-case basis. This review aims to consolidate relevant emerging real-world data and other key information about biosimilar-to-biosimilar cross-switching for prescribing clinicians. In the absence of clear clinical guidelines addressing this topic at present, this review may serve to facilitate discretionary and educated treatment decision making.
| S-EPMC8578069 | biostudies-literature
Project description:BackgroundRegulatory approval for a biosimilar product is provided on the basis of its comparability to an originator product. A thorough physicochemical and functional comparability exercise is a key element in demonstrating biosimilarity. Here we report the characterization of a proposed biosimilar rituximab (GP2013) and originator rituximab.ObjectiveTo compare GP2013 with originator rituximab using an extensive array of routine analytical and extended characterization methods.MethodsPrimary and higher order protein structures were analyzed using a variety of methods that included high-performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS), peptide mapping with UV and MS detection, circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy, hydrogen deuterium exchange (HDX) MS, 1D (1)H nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography and differential scanning calorimetry (DSC). Charge and amino acid modifications were assessed using cation exchange chromatography (CEX) and peptide mapping using reversed-phase (RP) HPLC. Boronate affinity chromatography was used to determine the relative amount of glycation. Glycans were identified and quantified after 2-aminobenzamide (2-AB) labeling and separation using normal phase HPLC with fluorescence and MS detection, respectively. Glycan site occupancy was determined using reducing capillary electrophoresis with sodium dodecyl sulfate (CE-SDS). Size heterogeneity was determined using reducing and non-reducing CE-SDS, size exclusion chromatography (SEC) and asymmetric flow field flow fractionation (AF4). Biological characterization included a series of bioassays (in vitro target binding, antibody-dependent cell-mediated cytotoxicity [ADCC], complement-dependent cytotoxicity [CDC] and apoptosis) and surface plasmon resonance (SPR) Fc receptor binding assays.ResultsIntact mass analysis of GP2013 and the heavy and light chains using RP HPLC-ESI-MS revealed the expected molecular mass of rituximab. The amino acid sequence was shown to be identical between GP2013 and the originator rituximab. Further sequence confirmation using RP-HPLC-UV/MS peptide mapping showed non-distinguishable chromatograms for Lys-C digested GP2013 and originator rituximab. The higher order structure of GP2013 was shown to be indistinguishable from originator rituximab using a large panel of redundant and orthogonal methods. GP2013 and originator rituximab were comparable with regard to charge variants, specific amino acid modifications and the glycan pattern. GP2013 was also shown to have similar purity, aggregate and particle levels when compared with the originator. Functionally, and by using a comprehensive set of bioassays and binding assays covering a broad range of rituximab's functional activities, GP2013 could not be distinguished from originator rituximab.ConclusionGP2013 was shown to be physicochemically highly similar to originator rituximab at the level of primary and higher order structure, post-translational modifications and size variants. An extensive functional characterization package indicated that GP2013 has the same biological properties as originator rituximab.
| S-EPMC3775154 | biostudies-literature