Multiple infliximab biosimilar switches appear to be safe and effective in a real-world inflammatory bowel disease cohort.

BACKGROUND: Switching from originator infliximab (IFX) to biosimilar IFX is effective and safe. However, data on multiple switching are scarce. The Edinburgh inflammatory bowel disease (IBD) unit has undertaken three switch programmes: (1) Remicade to CT-P13 (2016), (2) CT-P13 to SB2 (2020), and (3) SB2 to CT-P13 (2021). OBJECTIVE: The primary endpoint of this study was to assess CT-P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety. METHODS: We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT-P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, C-reactive protein (CRP), faecal calprotectin (FC), IFX trough/antibody levels, and drug survival. RESULTS: 297 patients (CD n = 196 [66%], ulcerative colitis/inflammatory bowel disease unclassified n = 101, [34%]) were switched (followed-up: 7.5 months [6.8-8.1]). This was the third, second and first IFX switch for 67/297 (22.5%), 138/297 (46.5%) and 92/297 (31%) of the cohort respectively. 90.6% of patients remained on IFX during follow-up. The number of switches was not independently associated with IFX persistence after adjusting for confounders. Clinical (p = 0.77), biochemical (CRP ≤5 mg/ml; p = 0.75) and faecal biomarker (FC<250 µg/g; p = 0.63) remission were comparable at baseline, week 12 and week 24. CONCLUSION: Multiple successive switches from IFX originator to biosimilars are effective and safe in patients with IBD, irrespective of the number of IFX switches.

Efficacy and safety of a new ranibizumab biosimilar CKD-701 using a pro re nata treatment regimen in neovascular age-related macular degeneration: A phase 3 randomized clinical trial.

PURPOSE: This study aimed to establish the efficacy, safety, and immunogenicity equivalence of the proposed biosimilar CKD-701 with the reference ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: A total of 312 participants with active subfoveal choroidal neovascularization were randomly assigned to either the CKD-701 (n = 156) or reference ranibizumab (n = 156) arms. The initial 3-month loading intraocular injections were followed by pro re nata (PRN) dosing for 9 months. The primary outcome was the proportion of patients with less than 15-letters of corrected visual acuity (BCVA) loss at 3 months visit (one month after last loading injection) compared to the baseline time point. The presence of retinal fluid, and changes in BCVA and central retinal thickness (CRT) were assessed as secondary efficacy outcomes. Immunogenicity and safety were evaluated in both treatment arms. RESULTS: In the CKD-701 arm, 143 (97.95%) patients lost <15 letters in the BCVA at 3 months compared to 143 (98.62%) in the reference arm (P = 0.67). The BCVA improved with a mean improvement of +7.0 (CKD-701) and +6.2 (ranibizumab) letters at 3 months (P = 0.43). The least-squares mean (SE) changes in CRT at 3 months from the baseline were -119.3 (12.0) µm and -124.5 (11.9) µm in the CKD-701 and ranibizumab groups, respectively (P = 0.74). The proportion of participants with subretinal or intraretinal fluid at 3, 6, and 12 months was similar between the study arms. The number (SE) of injections were 8.36 (3.13) in the CKD-701 and 8.26 (2.92) in ranibizumab (P = 0.62). The occurrence of adverse events and antidrug antibody in the study arms were also not statistically different. CONCLUSION: CKD-701 is a biosimilar to the reference ranibizumab in terms of efficacy, safety, and immunogenicity for the treatment of patients with nAMD. Moreover, improvement and maintenance of visual outcome were achieved through PRN regimen.

Adalimumab biosimilars in the therapy of Crohn´s disease and ulcerative colitis: Prospective multicentric clinical monitoring.

OBJECTIVE: The adalimumab biosimilars FKB327 and GP2017 were approved for the therapy of patients with inflammatory bowel disease (IBD). Relatively few prospective studies with biosimilar adalimumab in patients with IBD have been published. The aim of this prospective observational study was to evaluate the effectiveness and safety of the biosimilar adalimumab. MATERIAL AND METHODS: Adalimumab biosimilars FKB327 (Hulio®) and GP2017 (Hyrimoz®) were indicated to 50 naive patients in terms of biological therapy with Crohn's disease (CD) or ulcerative colitis (UC). Effectiveness of therapy was evaluated via the Crohn's Disease Activity Index [CDAI] or the Mayo Scoring System [MSS] in patients with CD or UC, respectively, before and after 12 weeks. Additional goals were to evaluate weight changes, laboratory tests and complications or adverse events of this therapy. RESULTS: In CD patients, remission (CDAI <150) was achieved in 73.5% of cases, partial response (≥70-point decrease in CDAI score from baseline) in 11.8%, no response in 11.8% and 2.9% patients discontinued therapy. In UC patients, remission (total score on partial Mayo index ≤2 points) was achieved only in 18.8% of cases, partial response (≥2-point decrease in partial Mayo score from baseline) in 43.8%, no response in 25.0% and 12.5% patients discontinued therapy. There were statistically significant improvements in CDAI, MSS, haemoglobin, fecal calprotectin, albumin and CRP serum levels after 12 weeks of therapy. Seven adverse events were identified, three of which resulted in therapy being discontinued. CONCLUSIONS: This prospective observational study proved the effectiveness of the adalimumab biosimilars FKB327 and GP2017 in IBD.

A randomized pharmacokinetic/pharmacodynamic study comparing the bioequivalence of potential biosimilar candidate P044 with reference medicine in healthy volunteers.

BACKGROUND: P044 is a proposed biosimilar candidate of Teriparatide for reference medicine, Forsteo®. This study was designed to evaluate the Pharmacokinetic/Pharmacodynamic (PK/PD) bioequivalence between P044 and Forsteo®. METHODS: In this randomized, open-label, single-dose, crossover study, 66 healthy female subjects were randomized to receive P044 and Forsteo®. The primary PK endpoints of the study were the area under the concentration versus time from zero to infinity (AUC0-inf) and maximum plasma concentration (Cmax). Secondary endpoints included area under the concentration versus time from zero to the last quantifiable concentration (AUC0-last) and Cmax for PD parameter, additional PK parameters and safety. RESULTS: Sixty-six subjects were enrolled in the study and baseline demographics were similar between the two treatments. The two treatments presented similar PK/PD parameters and the 90% confidence interval for primary and secondary endpoints were within the bioequivalence acceptance range (80.00-125.00%) for all parameters. None of the subjects experienced serious adverse event, and all of the reported adverse events were mild and similar between two treatments. CONCLUSIONS: This study demonstrated the PK/PD similarity of P044 to reference medicine, Forsteo® and safety profiles were comparable between treatments. TRIAL REGISTRATION: EudraCT Number: 2019-004477-82.

Primary Prophylaxis With Biosimilar Filgrastim for Patients at Intermediate Risk for Febrile Neutropenia: A Cost-Effectiveness Analysis.

PURPOSE: Temporary COVID-19 guideline recommendations have recently been issued to expand the use of colony-stimulating factors in patients with cancer with intermediate to high risk for febrile neutropenia (FN). We evaluated the cost-effectiveness of primary prophylaxis (PP) with biosimilar filgrastim-sndz in patients with intermediate risk of FN compared with secondary prophylaxis (SP) over three different cancer types. METHODS: A Markov decision analytic model was constructed from the US payer perspective over a lifetime horizon to evaluate PP versus SP in patients with breast cancer, non-small-cell lung cancer (NSCLC), and non-Hodgkin lymphoma (NHL). Cost-effectiveness was evaluated over a range of willingness-to-pay thresholds for incremental cost per FN avoided, life year gained, and quality-adjusted life year (QALY) gained. Sensitivity analyses evaluated uncertainty. RESULTS: Compared with SP, PP provided an additional 0.102-0.144 LYs and 0.065-0.130 QALYs. The incremental cost-effectiveness ranged from $5,660 in US dollars (USD) to $20,806 USD per FN event avoided, $5,123 to $31,077 USD per life year gained, and $7,213 to $35,563 USD per QALY gained. Over 1,000 iterations, there were 73.6%, 99.4%, and 91.8% probabilities that PP was cost-effective at a willingness to pay of $50,000 USD per QALY gained for breast cancer, NSCLC, and NHL, respectively. CONCLUSION: PP with a biosimilar filgrastim (specifically filgrastim-sndz) is cost-effective in patients with intermediate risk for FN receiving curative chemotherapy regimens for breast cancer, NSCLC, and NHL. Expanding the use of colony-stimulating factors for patients may be valuable in reducing unnecessary health care visits for patients with cancer at risk of complications because of COVID-19 and should be considered for the indefinite future.

Network meta-analysis of infliximab biosimilars for the treatment of rheumatoid arthritis.

PURPOSE: This article assesses the relative efficacy and safety of infliximab biosimilars in treatment of patients with rheumatoid arthritis (RA). METHODS: A frequentist, random-effects network meta-analysis was performed to evaluate evidence from randomized controlled trials that examined the use of infliximab biosimilars for treatment of patients with RA. PubMed/MEDLINE and other sources were searched for reports evaluating rates of response to treatment with the reference product (infliximab) vs an infliximab biosimilar. The primary efficacy outcome of interest was the rate of attainment of ACR20 (ie, 20% improvement in American College of Rheumatology core measures). The primary safety outcome was the rate of treatment-related serious adverse events (SAEs). Data were extracted by the primary author, and an assessment for risks of methodological bias was performed for each evaluated study. RESULTS: Five studies that enrolled a total of 2,499 patients were included. Overall comparisons using odds ratios and 95% confidence intervals (CIs) did not indicate statistically significant differences in response to treatment with biosimilar agents relative to each other or the infliximab reference product. ORs for ACR20 response for biosimilars vs infliximab were as follows: 1.475 (95% CI, 0.940-2.315) for infliximab-axxq, 1.259 (95% CI, 0.854-1.855) for infliximab-dyyb, 0.865 (95% CI, 0.5511.358) for infliximab-qbtx, and 0.832 (95% CI, 0.506-1.367) for infliximab-abda. Similar findings were observed in reported SAE rates among patients treated with the various biosimilars. CONCLUSION: ACR20 response appears to be comparable and nonsignificantly different between infliximab biosimilars. In the absence of any meaningful differences in safety or efficacy, biosimilar cost may be the deciding factor in choosing a treatment or agent for formulary inclusion.