Biosimilar Treatment Research Articles

A Bayesian model to analyse the association of comorbidities with biosimilar treatment retention in a non-medical switch scenario in patients with inflammatory rheumatic musculoskeletal diseases

ObjectivesTo analyse clinical outcomes of a non-medical switch from originator adalimumab (ADA) to its ABP501 biosimilar (ABP) over 6 months in patients with inflammatory rheumatic musculoskeletal diseases (RMD) in relation to comorbidity as a risk factor for therapy discontinuation.MethodsRMD patients switching from originator ADA to ABP were identified from a large routine database from October 2018 onwards. Documented clinical data at the time of non-medical switching (baseline), and at 3 and 6 months were collected. Comorbidities were represented by the Charlson Comorbidity Index (CCI) at baseline and patients were categorized based on CCI > 0. Differences in the ABP retention rate over 6 months between patients with CCI = 0 and patients with CCI > 0 were analysed using Bayesian exponential regression.ResultsA total of 111 patients with axial spondyloarthritis (n = 68), rheumatoid arthritis (n = 23) and psoriatic arthritis (n = 15), were identified, 74.8% of whom had continued treatment with ABP after 6 months, while a smaller proportion had either switched to another ADA biosimilar (10.8%), switched back to originator ADA (7.2%), switched to a different biologic (3.6%), or dropped out (3.6%). At baseline, a CCI > 0 was found in 38% of patients. Cardiovascular comorbidities (40%) were most prevalent followed by diseases of the skin (33%), the gastrointestinal tract (20%) and the eye (20%). ABP treatment was continued after 6 months in 74% of patients with CCI = 0 and in 76% with CCI > 0. Bayesian analysis showed only a small difference (months) in the APB continuation rate between groups (estimate 0.0012, 95% credible interval (CrI) -0.0337 to 0.0361). Adjusting for age, sex, and disease subtype revealed somewhat shorter retention rates for patients with CCI > 0, but the distribution of the difference included 0 (estimate -0.0689, 95% CrI -0.2246 to 0.0234).ConclusionIn a non-medical switch scenario of RMD patients, there was no evidence for a considerable difference in ABP retention rates over 6 months between comorbidity groups.

Potential of the domestic biosimile omalizumab in achievement of control in patients with severe asthma: short communication

BACKGROUND: Severe atopic asthma is a medical and social problem due to its prevalence, the tendency to exacerbations, the impact on the quality of life and on the work ability, and high treatment costs. The appearance biosimilar omalizumab among biologicals makes such therapy more accessible to patients. This article presents the results of an open prospective clinical study of the biosimilar omalizumab in patients with the severe atopic asthma.
 AIM: To evaluate the efficacy and tolerability of the domestically produced biosimilar omalizumab in the real clinical practice.
 MATERIALS AND METHODS: The study involved 15 adult patients (19–66 years) with a reliable history consistent with moderate to severe atopic asthma who hadn`t have asthma control at the time of inclusion in the study. All patients received the Genolar (omalizumab, Generic JSC, Russia) for 52 weeks at the dose calculated according to the instructions. The efficacy was evaluated taking into account changes in symptom severity, improved asthma control using the Asthma Control Questionnaire (ACQ-5), pulmonary function tests, peak flow measurements, assessment the asthma exacerbations number and the healthcare resources use.
 RESULTS: According to our study results, all patients demonstrated a decrease in the night and daytime attacks frequency and the shortness of breath severity due to omalizumab, which made it possible to reduce the basic therapy and refuse systemic glucocorticosteroids using in patients who previously received there. After 6 months we obtained an improvement in the asthma symptoms control: ΔACQ-5=-1.87 (p=0.0002) compared to baseline with a trend towards further improvement in indicators and reached ΔACQ-5=-2.18 (p=0.0001) to the 52nd week. We also obtained a statistically significant improvement in pulmonary function (after a year of treatment, the increase in forced expiratory volume in the first second was +19.85% compared to baseline, p=0.0001). No asthma exacerbation was registered during 12 months omalizumab treatment.
 CONCLUSION: Our study showed that the biosimilar treatment in patients with severe atopic asthma allowed to achieve asthma control, decrease the exacerbations number and reduce the basic therapy volume, including oral-corticosteroid elimination.

Treatment Patterns, Effectiveness, and Safety of Originator Insulin Glargine versus Insulin Glargine-yfgn within the Veterans Health Administration

We described insulin glargine (originator) and insulin glargine-yfgn (biosimilar) treatment patterns, assessed effectiveness and safety outcomes, and identified reasons for switching back to the originator product from the biosimilar. This retrospective study included 328,463 Veterans 18 years of age and older who received one or more outpatient prescriptions for insulin glargine and/or insulin glargine-yfgn between 1 June 2021 and 31 December 2022. Patients were assigned to subgroups based on the initial prescription during the study period, prevalent versus incident use for originator insulin glargine, and prior versus no prior use of the originator before the biosimilar (i.e., prevalent originator non-switcher (n = 189,734), originator switch to biosimilar (n = 81,010), incident originator non-switcher (n = 49,401), and incident biosimilar (n = 8318)). There were no differences in the outcome of mean HbA1c (7.9% for all subgroups). There were also no differences in the unadjusted rates of hospitalization and/or emergency room visits for hyper- and hypoglycemia between the prevalent originator non-switcher and originator switched to biosimilar subgroups (p = 0.09 and 0.38, respectively) or the incident originator non-switcher and incident biosimilar subgroups (p = 0.054 and 0.61, respectively). Finally, none of the HbA1c or hyperglycemia outcomes adjusted for baseline characteristics were statistically different. Adjusted analyses for rates of hospitalization and/or emergency room visits for hypoglycemia could not be performed due to the low number of events. Overall, patients who received insulin glargine-yfgn had similar effectiveness and safety outcomes as patients who received the originator.

A contrast-enhanced ultrasound-based nomogram for the prediction of therapeutic efficiency of anti-PD-1 plus anti-VEGF agents in advanced hepatocellular carcinoma patients.

There is no study focusing on noninvasive predictors for the efficacy of sintilimab (anti-PD-1) plus IBI305 (a bevacizumab biosimilar) treatment in advanced hepatocellular carcinoma (HCC). A total of 33 patients with advanced HCC were prospectively enrolled and received sintilimab plus IBI305 treatment from November 2018 to October 2019. Baseline characteristics including clinical data, laboratory data, and tumor features based on pretreatment CT/MR were collected. Meanwhile, pretreatment contrast-enhanced ultrasound (CEUS) for target tumor was performed and quantitative parameters were derived from time-intensity curves (TICs). A nomogram was developed based on the variables identified by the univariable and multivariable logistic regression analysis. The discrimination, calibration, and clinical utility of the nomogram were evaluated. Tumor embolus and grad ratio were significant variables related to the efficacy of sintilimab plus IBI305 strategy. The nomogram based on these two variables achieved an excellent predictive performance with an area under curve (AUC) of 0.909 (95% CI, 0.813-1). A bootstrapping for 500 repetitions was performed to validate this model and the AUC of the bootstrap model was 0.91 (95% CI, 0.8-0.98). The calibration curve and decision curve analysis (DCA) showed that the nomogram had a good consistency and clinical utility. This study has established and validated a nomogram by incorporating the quantitative parameters of pretreatment CEUS and baseline clinical characteristics to predict the anti-PD-1 plus anti-VEGF treatment efficacy in advanced HCC patients.

An online survey among US patients with immune-mediated conditions: Attitudes about biosimilars.

BACKGROUND: Few surveys about biosimilars have been conducted among US patients. OBJECTIVE: To evaluate attitudes about biosimilars among patients with rheumatoid arthritis (RA), psoriasis and/or psoriatic arthritis (PsO/A), and/or inflammatory bowel disease (IBD). METHODS: WebMD, LLC fielded a 16-item online survey to members of the US Dynata consumer panel meeting these criteria: aged 18 years or older; self-reported specialist diagnosis of RA, PsO/A, or IBD of at least 1 year; and not currently receiving an infliximab biosimilar. A quota of 500 was set, stratified by region and condition. The survey was exempt by the institutional review board, exploratory, and not registered. RESULTS: Overall, 44% (n = 221) of patients were on a biologic; 56% (n = 279) were not on a biologic (40% [n = 199] were biologic naive and 16% [n = 80] used biologics in the past). Among all patients, 66% were unaware of biosimilars and 24% were aware (10% unsure). After being shown the US Food and Drug Administration definition of a biosimilar, main concerns were side effects (59%), long-term safety (50%), and not knowing a lot (46%). Among current users, 43% would switch to a biosimilar and 26% would not (32% unsure). Of those unwilling to switch, 51% were concerned about side effects, 42% about financial support, and 40% about efficacy. When those not on a biologic were asked if their doctor prescribed an original anti-tumor necrosis factor α but their insurance required its biosimilar, 49% would switch and 8% would not (43% unsure). 51% of patients surveyed thought pharmacist-level substitution of an interchangeable biosimilar was acceptable with notification. Survey findings were consistent among the RA, PsO/A, and IBD subgroups. CONCLUSIONS: Although two-thirds of patients surveyed were unaware of biosimilars, the majority were potentially receptive to biosimilar treatment after being provided with the definition of a biosimilar. Patients expressed a desire to know more about biosimilars in general, how they compare with original biologics, their benefits, and cost. DISCLOSURES: This study was funded by Boehringer Ingelheim Pharmaceuticals Inc. (BIPI). WebMD, LLC, fielded the survey. BIPI was given the opportunity to review the article for medical and scientific accuracy and intellectual property considerations. Dr Gibofsky is a consultant/advisor for AbbVie Inc., Biosplice Therapeutics, Lilly, Novartis Pharmaceuticals Corporation, and Pfizer Inc., and he is on the speakers' bureau for AbbVie Inc., Amgen, Lilly, and Pfizer Inc., and has stock ownership in AbbVie Inc., Amgen, Bristol-Myers Squibb Company, Horizon Pharma plc, and Pfizer Inc. Dr Peyrin-Biroulet reports that he has received personal consulting fees from Merck Sharp & Dohme, AbbVie, Janssen, Takeda, Celltrion, Pfizer, Bristol-Myers Squibb Company, Pharmacosmos, Shire, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, UCB-Pharma, Hospira, BIPI, and Lilly. Dr McCabe is an employee of BIPI. Dr McGrath was an employee of BIPI at the time the survey was conducted. Mr Jacobson, Mr Franklin, and Ms O'Hara-Levi report no disclosures.

The Perception among Israeli Gastroenterologists Regarding Treatment of Patients with Biosimilar Medications

Background and Objectives: The ever-expanding entry of biosimilar drugs into the Israeli market requires doctors to decide whether to prescribe these medications. We aimed to assess the prevalence of biosimilar use and Israeli gastroenterologists' knowledge, experience, and perception of biosimilar treatment. Materials and Methods: A cross-sectional survey was conducted among Israeli Gastroenterology Association (IGA) members between March and May 2022 using a structured 20-item questionnaire. Results: The questionnaire was completed by 108 gastroenterologists. Sixty-two percent prescribed biosimilars to their patients in the past year. Most of the patients (81%) were biologically naïve and only 19% were switched to a biosimilar. Most gastroenterologists (75%) answered that the effectiveness is the same. The rates of resistance to switching were 19%, 36%, and 70% for patients in remission for over two years, pregnant women, and difficulty reaching remission, respectively. In cases seeing a lack of response after switching, most physicians chose to change the mechanism of action, with only a small percentage returning to the brand-name drug. Conclusions: Most Israeli gastroenterologists are not concerned about biosimilars' safety and efficacy. Despite this, most physicians will prefer the brand-name drug, especially regarding adalimumab. The populations in which physicians most oppose switching are those who have had difficulty achieving remission and pregnant women.

Severe Hypersensitivity Reactions at Biosimilar versus Originator Rituximab Treatment Initiation, Switch and Over Time: A Cohort Study on the French National Health Data System.

Biosimilar products of rituximab came to market in 2017. French pharmacovigilance centers have highlighted an excess of case reports of severe hypersensitivity reactions related to their use compared with the originator product. The aim of this study was to assess the real-world association between biosimilar versus originator rituximab injections and hypersensitivity reactions, among initiators and switchers, at first injection and over time. The French National Health Data System was used to identify all rituximab users between 2017 and 2021. A first cohort consisted of patients who initiated rituximab (originator or biosimilar), while a second cohort consisted of originator-to-biosimilar switchers, matched on age, sex, deliveries history, and pathology, with one or two patients still receiving the originator product. The event of interest was defined as a hospitalization for anaphylactic shock or serum sickness following a rituximab injection. A total of 91,894 patients were included in the initiation cohort-17,605 (19%) with the originator product and 74,289 (81%) with a biosimilar. At initiation, 86/17,605 (0.49%) and 339/74,289 (0.46%) events occurred in the originator and biosimilar groups, respectively. The adjusted odds ratio of biosimilar exposure associated with the event was 1.04 (95% confidence interval [CI] 0.80-1.34), and the adjusted hazard ratio for biosimilar versus originator exposure was 1.15 (95% CI 0.93-1.42), showing no increased risk of event with biosimilar use at first injection, and over time. 17,123 switchers were matched to 24,659 non-switchers. No association was found between switch to biosimilars and occurrence of the event. Our study does not support any association between exposure to rituximab biosimilars versus originator and hospitalization for a hypersensitivity reaction, either at initiation, at switch, or over time.

Medical Oncologists' Knowledge and Perspectives on the Use of Biosimilars in the United States.

Despite increasing availability of biosimilar cancer treatments, little is known about oncologists' knowledge and concerns regarding biosimilar use in the United States. We surveyed medical oncologists to examine their knowledge, attitudes, and experience with biosimilars. Oncologists recruited via the ASCO Research Survey Pool completed a 29-question survey in 2020 designed with input from clinical and health care system experts and literature review. Of the 269 respondents, most treated patients with biosimilars (n = 236, 88%) and reported that biosimilars were required at their institution (n = 168, 63%). Approximately half (n = 140, 52%) of oncologists correctly responded that biosimilars were not the same as generic medicines. Commonly reported barriers to use of biosimilars included concerns regarding a perceived lack of relevant research (n = 85, 33% reporting quite a bit/very much), the potential for extrapolation (n = 83, 33%), and efficacy limitations (n = 77, 30%). More oncologists from university hospitals (n = 36, 22%) than from community/private hospitals (n = 28, 38%) or private practices (n = 13, 38%) were concerned about biosimilar efficacy. A high proportion of oncologists reported that information on safety (n = 259, 99%) and efficacy (n = 255, 99%) is important when considering whether to use biosimilars. Less than half reported that their institution provided education about biosimilars (n = 108, 40%). In this sample of medical oncologists, knowledge about basic features of biosimilars was limited and access to information about biosimilars was insufficient. The present study determined that educational programs on biosimilars for oncologists are needed and identified priorities for such efforts.

Identification of Barriers Preventing Biosimiliar Oncology Medication Adoption.

(1) Background: A biosimilar is a biologic medical product that has been approved by the United States Food and Federal Drug Administration (FDA) and is an almost identical copy of an original biologic product yet manufactured by a different company. Biosimilars are often assumed to be the same as generic medications, while often made from living organisms. Through clinical trials, biosimilars have been shown to be both as safe and as effective as their originator products. Biosimilars have also proven they can reduce the costs to both insurance companies and patients in many circumstances. However, despite their cost savings, biosimilar manufacturers continue to face barriers in having oncologists and cancer centers prescribe them for their patients. This review aims to identify barriers associated with medical provider prescriptive behaviors related to biosimilars for patients. (2) Methods: Reviewers analyzed 27 articles and identified common themes. (3) Results: After a thorough literature review, the researchers identified seven barriers to prescribing of biosimilars: physician comfort in originators instead of biosimilars, patient reluctance to switch from a current biologic to a biosimilar, provider profits associated with an originator biologic, lack of stakeholder education on biosimilars, lack of provider team knowledge of biosimilars, lack of knowledge surrounding the biosimilar FDA approval process, and hesitancy to stock multiple drugs for a specific indication. (4) Conclusions: This review's findings of identified barriers to use of biosimilars provides insight for healthcare providers and organizations surrounding prescribing practices and potential treatment benefits for cancer patients who may benefit from biosimilar treatment medications.

Long-term efficacy and safety of RazumabTM (biosimilar ranibizumab) in Indian patients with retinal diseases: results from retrospective REAR RD-2 study

<p><strong>Background:</strong> To evaluate risk factors associated with retinal diseases and efficacy and safety of Razumab<sup>TM</sup> (biosimilar ranibizumab) in the management of retinal diseases in Indian patients with wet age-related macular degeneration (wet AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and myopic choroidal neovascularization (mCNV).</p><p><strong>Methods:</strong> In the retrospective, observational REAR RD-2 study, all patients with retinal diseases who were treated with biosimilar ranibizumab were included from multiple Indian sites. The demographic parameters, disease characteristics and treatment details were recorded. Efficacy assessments included improvement in best corrected visual acuity (BCVA), and decrease in central subfield thickness (CSFT), intra-retinal fluid (IRF) and sub-retinal fluid (SRF) from baseline to week 48.</p><p><strong>Results:</strong> Data of 1422 patients (wet AMD-27.57%; DME-30.7%, RVO-33.47%; mCNV-5.48%), who were treated with biosimilar ranibizumab, was analyzed. The most common age group of patients was 61-70 years (36.6%). The most common ocular risk factor identified was glaucoma (24.90%). A total of 85.72% patients were treatment naïve and 14.28% were previously treated patients. Biosimilar ranibizumab treatment resulted in significant (p<0.05) improvements in the mean BCVA and CSFT, and the proportion of patients with IRF and SRF was significantly reduced throughout the treatment. No new safety concerns with biosimilar ranibizumab were observed.</p><p><strong>Conclusions:</strong> Retinal diseases are more common in the age group of 61-70 years. Glaucoma was the most common ocular risk factor identified for retinal diseases. Long-term treatment with biosimilar ranibizumab was effective and well-tolerated in retinal diseases including wAMD, DME, RVO and mCNV in real-world Indian scenario. </p><p><strong> </strong></p>

Shaping inflammatory bowel disease care through patient choice and joint decision-making

Patient choice and shared decision-making are priorities in the treatment of inflammatory bowel disease (IBD). The choices facilitated by UK IBD services were affected by the COVID-19 pandemic from when it began to affect the UK in early 2020, with an almost overnight stoppage of face-to-face outpatient clinic appointments and a recognition that some IBD treatments, such as steroids, may have a negative impact on patient outcome. Many IBD services struggled with staff redeployment and growing demand from unwell and concerned patients. Subsequent changes in treatment pathways resulted in some patients accessing biologic therapies at earlier stages than previously. The need to involve patients in decisions regarding their care became more important than ever, due to the potential impact of the pandemic on their disease and treatment pathway. This impact interacted with other key factors affecting patient choice, such as the perceived and real-world costs of biologic and biosimilar treatments. This review looks at how COVID-19 affected patient choice and how IBD clinical nurse specialists can use the principles of joint decision-making to move forward in developing IBD services for the future. Declaration of interest This article was commissioned and funded by Takeda UK Ltd, who suggested the author and topic. Takeda UK Ltd also reviewed and approved the content. Prescribing information can be found at the end of the article.

Moving forward: Implementing health psychology research to improve patient acceptance of biosimilars.

As more biosimilars enter the pharmaceutical market, patient acceptance remains a significant barrier to their uptake. Psychological factors, such as negative expectations, are important causes of patient hesitancy. As a result, patients can develop nocebo responses following a transition, discontinue biosimilar treatment early, or have poor adherence. These negative outcomes may offset some of the cost-saving potential of biosimilars. Key healthcare professionals such as pharmacists, physicians, and nurses already play a noteworthy role in educating and transitioning patients. However, given the psychological aspect of biosimilar acceptance, it is logical for healthcare professionals and researchers to draw on research and theory from health psychology. This commentary outlines how a multidisciplinary approach can add to the understanding of the mechanisms behind patient resistance to biosimilars and help engage patients in the transitioning process. It also explores how health psychology strategies that have been successful in similar areas can be translated to help conduct more effective transitions. Future directions in research are discussed.

HSD55 Non-Interventional, Real-World Study of Patients with Early Stage, Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer Receiving Biosimilar Trastuzumab

Biosimilar trastuzumab (trastuzumab-qyyp) was the fourth trastuzumab biosimilar in Europe in 2018. The objectives of this study were to understand the utilization of biosimilar trastuzumab and its benefits and risks in a real-world setting. Materials and methods: In this observational study, patients in the Netherlands and Norway treated with biosimilar trastuzumab for early stage (stage 0-3) HER2+ breast cancer were recruited (February 2020-July 2021). Data recorded were biosimilar trastuzumab treatment patterns, patient demographics, clinical characteristics, tolerability, and healthcare resource utilization (HCRU).

Patient-Reported Outcomes in Rheumatoid Arthritis: A Key Consideration for Evaluating Biosimilar Uptake?

PurposeThis review aims to provide an overview of the impact of TNFis biosimilars, with marketing authorization, in patient-reported outcome measures (PROMs) scores and explore how PROMs endpoints might add value in biosimilars uptake in RA patients.Patients and MethodsA comprehensive search of Medline, Scopus, Lilacs, and CINAHL databases was performed for papers published between January 2012 and December 2021. For inclusion, studies had to be prospective, published in a peer-reviewed journal, published in English or Spanish language; studies using PROMs as an outcome measure. After screening title and abstracts and assessing the remaining full texts fulfilling the inclusion criteria, 31 papers were used in this narrative review.ResultsPROMs were used as secondary outcomes in included studies. The most frequently employed domains to assess biosimilar efficacy include physical function, patient global assessment (PtGA), health-related quality of life (HRQoL), and fatigue. The results of randomized clinical trials uniformly showed that mean change in PROMs scores is comparable between biosimilar and reference biologic treatment groups. However, open-label and real-world studies revealed high rates of discontinuation of therapy, mainly for subjective worsening of disease activity or non-specific adverse events. Even without objective clinical evidence of inflammation, patients who are considered to have active disease (higher scores on PtGA) have higher discontinuation rates of biosimilars. The available information suggests that the nocebo effect is the most likely cause for the discontinuation of biosimilars.ConclusionThere is scarce literature surrounding the impact of biosimilars in PROMs, especially in open-label studies. In real-life studies, biosimilars have a higher discontinuation rate than reference products. TNFis biosimilars treatment efficacy in RA depends on disease activity and other factors such as PtGA and fatigue. The nocebo effect is the best explanation for biosimilar’s discontinuation.

P683 Discontinuation of infliximab treatment: a comparison between IBD patients who retransitioned to originator and those who remained on biosimilar

Abstract Background Since the introduction of infliximab biosimilars, many patients with inflammatory bowel disease (IBD) transitioned from originator (Remicade) to an infliximab biosimilar, mainly for cost containment. Studies showed that, despite proven biosimilarity, 2 to 16.5% of patients who transition to biosimilar, retransition to infliximab originator (stopped biosimilar and re-initiated originator), mainly due to increased disease activity or (subjective) adverse events. It is unclear whether this unsatisfactory treatment response is related to the product or to the patient and his/her disease. This study aimed to compare the risk of infliximab treatment discontinuation between patients who retransitioned from infliximab biosimilar to originator and patients who remained on infliximab biosimilar. Methods IBD patients treated at the Medisch Spectrum Twente or Spaarne Gasthuis who transitioned from Remicade to an infliximab biosimilar between January 2015 and September 2019 were eligible for inclusion. Patients who retransitioned to Remicade were included in the retransitioning cohort and matched with up to 3 patients who remained on biosimilar (biosimilar cohort). Patients were matched on: hospital, calendar date of biosimilar transitioning and duration of biosimilar treatment. Patients were followed until discontinuation of infliximab (>16 weeks no administration, or switch to another biological). Risk of infliximab discontinuation (overall discontinuation and stratified into switching to another biological or discontinuation without switching) was compared using a (adjusted) conditional Cox proportional hazards model. Results The retransitioning cohort comprised 42 patients and the biosimilar cohort comprised 120 patients. Baseline characteristics of the cohorts were similar, but dosing interval was shorter in the retransitioning cohort (44 versus 56 days). Infliximab treatment discontinuation was 24.6% in the retransitioning cohort compared to 6.7% in the biosimilar cohort at 12 months (p<0.01) (Figure 1). Patients in the retransitioning cohort had a more than twofold risk (HR 2.5, 95%CI 1.3–5.1) for discontinuing infliximab treatment compared to patients in the biosimilar cohort. When analyzing the type of discontinuation, patients in the retransitioned cohort had a fivefold risk for switching to another biological (HR 4.8, 95%CI 0.6–37.0) and over a twofold risk for discontinuing without switching (HR 2.4, 95%CI 1.1–5.5) (Table 1). Conclusion Retransitioned patients have an increased risk for infliximab discontinuation, including both switching to another biological or discontinuing without switching. Our results indicate that retransitioning is mainly patient or disease related and less likely to be product related.

Ranibizumab Biosimilars for Neovascular Age-related Macular Degeneration, Macular Oedema with Retinal Vein Occlusion and Myopic Choroidal Neovascularization

Multiple disorders, such as neovascular age-related macular degeneration, diabetic macular oedema and myopic choroidal neovascularization require anti-vascular endothelial growth factor treatments to preserve and improve vision. In the last few decades, a multitude of options has arisen allowing for the best possible results. While the success of these drugs has been indisputable, the expiration or pending expiration of their patents creates an avenue for biosimilar medications to enter the market. These biosimilars can be produced at a discount compared with the original medications, with the possibility of a lower economic burden. However, they do not undergo as rigorous an approval process as innovator medications, leaving concerns about the heterogeneity of their clinical profile or side effects. This review will focus on the available biosimilar treatments, as well as the clinical trials evaluating them.

Long-Term Safety and Effectiveness of PF-05280014 (a Trastuzumab Biosimilar) Treatment in Patients with HER2-Positive Metastatic Breast Cancer: Updated Results of a Randomized, Double-Blind Study.

BackgroundPF-05280014 was compared with trastuzumab sourced from the European Union (trastuzumab-EU), each plus paclitaxel, as first-line treatment for human epidermal growth factor receptor 2-positive metastatic breast cancer in a phase III study. Equivalence between treatment groups was demonstrated.ObjectiveThe aim of this study was to report long-term safety and overall survival (OS) over 6 years after the first patient was screened.Patients and methodsRandomized patients received intravenous PF-05280014 or trastuzumab-EU, each plus paclitaxel, until objective disease progression. OS, long-term safety, subgroup safety (patients ongoing after day 378), and time-to-treatment discontinuation (TTD) were assessed based on the final statistical analysis plan amended for the ad-hoc analyses.ResultsOf 707 randomized patients (n = 352, PF-05280014; n = 355, trastuzumab-EU), 252 (71.6%) in the PF-05280014 and 251 (70.7%) in the trastuzumab-EU group discontinued treatment due to objective progression. Overall, 451 (63.8%) patients completed the study. Between groups (PF-05280014; trastuzumab-EU), estimated median TTDs were 12.25 and 12.06 months (p = 0.692); 61 (17.3%) and 67 (18.9%) patients died; stratified hazard ratio for OS was 0.929 (95% confidence interval 0.656–1.316; p = 0.339); estimated survival rates were 82.3 and 77.4% at 2 years and 77.2 and 75.3% at 3 years. The incidences of treatment-emergent adverse events (TEAEs) overall (98.6%; 96.6%) and for grades ≥3 (41.0%; 43.1%) were comparable between groups. In patients (n = 265; n = 264) ongoing after day 378, the incidences of any TEAEs, grade ≥3 TEAEs, and serious TEAEs were comparable between the treatment groups.ConclusionLong-term safety and OS were consistent with previous results and demonstrated no clinically meaningful differences between treatment groups.Trial registrationClinicalTrials.gov: NCT01989676 (21 November 2013); and EudraCT: 2013-001352-34 (18 December 2013).Supplementary InformationThe online version contains supplementary material available at 10.1007/s40259-021-00513-7.

Toward the integration of biosimilars into pediatric rheumatology: adalimumab ABP 501 experience of PeRA research group

ABSTRACT Objectives To review the real-life data, to provide an input to the literature concerning treatment of juvenile idiopathic arthritis (JIA) with adalimumab (ADL) biosimilar. Method This multi-centric retrospective study was conducted among children with JIA, followed up for at least 24-weeks from the initiation of ADL biosimilar (ABP 501) treatment. Adverse events and alterations in disease activity scores were figured out. Results The median age of the group was 15.5 (5–18) years. JIA categories were oligoarticular (n =12), enthesitis-related (ERA) (n=24), psoriatic (PsA) (n=6), and polyarticular (n=4). Uveitis was detected at the initiation of the disease (n=3), during the disease course (n=5), or before the diagnosis (n=1). The first-line treatment preferences were ADL biosimilar (n=37) and etanercept (n=9). On the 6th month of ABP 501, 40 (86.9%) patients had achieved complete remission. Six patients (1 PsA, 1 polyarticular JIA, and 4 ERA) had ongoing active arthritis. Furthermore, all except one of the patients had remission of ophthalmologic findings. No life-threatening adverse events were observed. Conclusions ABP 501 has a gradual increase in prescription in pediatric rheumatology. Real-life data of the cohort announce that ADL biosimilar is a suitable and effective treatment option for patients with JIA in case of indication.

Development of pulmonary sarcoidosis in Crohn\u2019s disease patient under infliximab biosimilar treatment after long-term original infliximab treatment: a case report and literature review

BackgroundInflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract, although its etiology has largely been unclear. Tumor necrosis factor inhibitors (TNF-I) are effective for the treatment. Recently, biosimilars of TNF-I, such as CT-P13, have been developed and are thought to possess equal efficacy and safety to the original TNF-I. Sarcoidosis is also a systemic granulomatous disease of unknown etiology. In steroid-resistant cases of sarcoidosis, TNF-I have been reported effective for achieving resolution. However, the progression of sarcoidosis due to the TNF-I also has been reported. We herein report a case of pulmonary sarcoidosis with a Crohn’s disease (CD) patient developed after a long period administration (15 years) of TNF-I.Case presentationsA 37-year-old woman with CD who had been diagnosed at 22 years old had been treated with the TNF-I (original infliximab; O-IFX and infliximab biosimilar; IFX-BS). Fifteen years after starting the TNF-I, she developed a fever and right chest pain. Chest computed tomography (CT) revealed clustered small nodules in both lungs and multiple enlarged hilar lymph nodes. Infectious diseases including tuberculosis were negative. Bronchoscopic examination was performed and the biopsy specimens were obtained. A pathological examination demonstrated noncaseating granulomatous lesions and no malignant findings. TNF-I were discontinued because of the possibility of TNF-I-related sarcoidosis. After having discontinued for four months, her symptoms and the lesions had disappeared completely. Fortunately, despite the discontinuation of TNF-I, she has maintained remission.ConclusionsTo our knowledge, this is the first case in which sarcoidosis developed after switching from O-IFX to IFX-BS. To clarify the characteristics of the cases with development of sarcoidosis during administration of TNF-I, we searched PubMed and identified 106 cases. When developing an unexplained fever, asthenia, uveitis and skin lesions in patients with TNF-I treatment, sarcoidosis should be suspected. Once the diagnosis of sarcoidosis due to TNF-I was made, the discontinuation of TNF-I and administration of steroid therapy should be executed promptly. When re-starting TNF-I, another TNF-I should be used for disease control. Clinicians should be aware of the possibility of sarcoidosis in patients under anti-TNF therapy.

Oncologists’ knowledge and perspectives on the use of biosimilars.

35 Background: Despite the increasing availability of biosimilar cancer treatments, little is known about oncologists’ knowledge and concerns about biosimilar use in the United States. We conducted a survey of oncologists to examine their knowledge, attitudes, and experience with biosimilars. Methods: Using the ASCO Survey Research Pool (10-6-20 to 11-16-20), clinical oncologists completed a 29-question survey designed with structured input from clinical and health care system experts and literature review. Results: Of the 269 respondents, most ( n= 236, 88%) treated with biosimilars and reported that biosimilars were required at their institution. The table summarizes participants’ knowledge, barriers to use, preferences for and access to information around biosimilars, and interest in training. Conclusions: Despite high uptake of biosimilars, knowledge about basic features of biosimilars was low, and oncologists in community and private practice settings were more often concerned about safety and efficacy than those in academic practices. This information provides targets for future education about biosimilars.[Table: see text]