Non-medical Switching Research Articles

Potential Cost Implications of Mandatory Non-Medical Switching Policies for Biologics for Rheumatic Conditions and Inflammatory Bowel Disease in Canada.

In 2018, TNFα inhibitors were the highest cost drug class for Canadian public drug programs. In 2019, two Canadian provinces announced mandatory nonmedical switching policies in an attempt to reduce their costs by increasing biosimilar uptake. The national impact of similar policies across Canada is unknown. We conducted a cross-sectional analysis of monthly publicly funded prescription claims for infliximab, etanercept, and adalimumab between June 2015 and December 2019. We reported the market share of biosimilars for infliximab and etanercept in 2019 for each province and estimated the cost savings that public payers could have realized in 2019 if mandatory switching policies had been implemented across Canada, including a sensitivity analysis, which assumed that governments receive a 25% rebate on all biologics. Provincial drug programs spent CAD $991.84million on infliximab, etanercept, and adalimumab in 2019, and, when biosimilars were available, they constituted only 15.5% of national utilization of these drugs. In British Columbia, the implementation of a mandatory switching policy for patients with rheumatic conditions increased the biosimilar market share of infliximab and etanercept by 299% (from 19.7% to 78.5%). If applied nationwide to all three biologics for all indications, we estimate such policies could lead to annual savings of between CAD $179.71million and CAD $425.64million nationally. The overall market share of biosimilars remains low in all provinces where mandatory switching policies have not been introduced. The cost implications of successfully increasing biosimilar uptake would be substantial, particularly as more biosimilars reach the Canadian market.

S0820 Real World Comparison of Bio-Originator Infliximab vs the Biosimilar Infliximab-abda in the Treatment of Inflammatory Bowel Disease

INTRODUCTION: Biologic therapies are indicated for the management of moderate-to-severe inflammatory bowel disease (IBD), including both Crohn’s disease (CD) and Ulcerative Colitis (UC). Biosimilars, biologic compounds that are similar but not identical to originator biologic therapies, have been developed for the management of a variety of immune mediated inflammatory disorders, including IBD, with similar efficacies and safety profiles to bio-originators. The primary aim of this study is to evaluate the efficacy and safety of biosimilars in IBD patients who were authorized for a non-medical switch from bio-originator infliximab to biosimilar infliximab-abda compared to patients who were maintained on originator therapy at the Cleveland Clinic. METHODS: This prospective observational cohort study was approved on 12/4/2019 by the institutional review board. IBD patients receiving infliximab and infliximab-abda infusions from 2018-2019 were identified. These charts were reviewed for characteristics listed in Table 1; surrogate markers of disease were used as noted in the table. Comparisons were made between cohorts using non-parametric testing for continuous variables and categorical variables (Table 1). A P-value of ≤0.05 was considered significant. RESULTS: Between Jan 2018 and Dec 2019, 359 patients were identified. 99 were switched from infliximab to infliximab-abda and 101 were continued on infliximab. Baseline demographics were similar between the two groups (Table 1). Both the infliximab-abda and infliximab groups had a higher proportion of patients with CD than UC at 63.6% and 74.3%, respectively. There was no significant difference in the use of corticosteroid taper and maintenance, fecal calprotectin, infliximab concentrations, and antibody levels. Although there was a significant difference in the CRP between patients that were switched compared to patients maintained on bio-originator, the differences are not clinically significant. Emergency department visits and inpatient admissions were similar between the two groups. Similar paired comparisons between patients pre- and post-switch showed no significant differences (Table 2). CONCLUSION: In a large cohort of patients receiving infusions at the Cleveland Clinic, our study demonstrates that a non-medical switch from bio-originator infliximab to biosimilar infliximab-abda was as safe and efficacious as continuing bio-originator therapy for IBD.Table 1.: Patients Switched to Infliximab-abda versus Patients Continued on InfliximabTable 2.: Patients Switched From Infliximab to Infliximab-abda As Self-Controls

Efficacy and safety of a single switch from etanercept originator to etanercept biosimilar in a cohort of inflammatory arthritis

AntiTNF-α biosimilars are broadly available for the treatment of inflammatory arthritis. There are a lot of data concerning the maintenance of clinical efficacy after switching from originators to biosimilars; therefore, such a transition is increasingly encouraged both in the US and Europe. However, there are reports about flares and adverse events (AE) as a non-medical switch remains controversial due to ethical and clinical implications (efficacy, safety, tolerability). The aim of our work was to evaluate the disease activity trend after switching from etanercept originator (oETA-Enbrel) to its biosimilar (bETA-SP4/Benepali) in a cohort of patients in Turin, Piedmont, Italy. In this area, the switch to biosimilars is stalwartly encouraged. We switched 87 patients who were in a clinical state of stability from oETA to bETA: 48 patients were affected by Rheumatoid Arthritis (RA),26 by Psoriatic Arthritis (PsA) and 13 by Ankylosing Spondylitis (AS).We evaluated VAS-pain, Global-Health, CRP, number of swollen and tender joints, Disease Activity Score on 28 joints (DAS28) for RA, Disease Activity in Psoriatic Arthritis (DAPSA) for PsA, Health Assessment Questionnaire (HAQ) and Health Assessment Questionnaire for the spondyloarthropathies (HAQ-S),Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. 11/85 patients (12.6%) stopped treatment after switching to biosimilar etanercept. No difference was found between oETA and bETA in terms of efficacy. However, some arthritis flare and AE were reported. Our data regarding maintenance of efficacy and percentage of discontinuation were in line with the existing literature.

The Challenges of Switching Therapies in an Evolving Multiple Biosimilars Landscape: A Narrative Review of Current Evidence.

With the increasing availability of biosimilars, the practice of switching therapies for non-medical reasons between an originator biologic and an analogous biosimilar has become more common. The evidence to support this practice mostly comes from single-switch randomized controlled trials (RCTs) and real-world (RW) evidence studies. However, as more biosimilars of the same originator enter the market, multiple switching events between originators and biosimilars is becoming a reality, despite limited evidence to support the efficacy and safety of such practice. Some countries have established guidelines, policies, or laws related to interchangeability and/or automatic substitution, whereas others have left these practices unregulated or controlled by other components of the healthcare system. Collectively, guidelines on single non-medical switching are often vague, with even less focus given to multiple non-medical switching, leaving this practice mostly unregulated. This narrative review will first discuss the current regulatory perspectives on non-medical switching and challenges associated with switching therapies, particularly with the availability of multiple biosimilars. We will then review the current evidence from RCTs and RW studies in the light of three different multiple-switch scenarios currently taking place in clinical practice: switching between an originator and a single biosimilar, switching between biosimilars of the same originator, and the clinical practice of switching back to the originator (i.e., switchbacks) after a failure of the initial non-medical switch to the analogous biosimilar.

The Impact of a Forced Non-Medical Switch of Inhaled Respiratory Medication Among Patients with Asthma or Chronic Obstructive Pulmonary Disease: A Patient Survey on Experience with Switch, Therapy Satisfaction, and Disease Control.

PurposeBudesonide/formoterol pressurized metered-dose inhaler (pMDI) was removed from a Medicare Part D formulary, and patients switched to fluticasone-based dry powder inhaler (DPI) therapies. This study describes the experience, satisfaction, and disease control among patients with asthma or chronic obstructive pulmonary disease (COPD) who switched due to removal from the formulary.Patients and MethodsA patient survey was conducted among adults with asthma or COPD who used budesonide/formoterol pMDI for ≥3 months prior to the formulary block and the new medication for ≥3 weeks after switching, recruited by providers in a research panel. Survey comprised both validated instruments (PASAPQ, OEQ, ACQ-6, and CAT) and stand-alone questions. Patient characteristics, switch experience, device and treatment satisfaction, onset of effect, and disease control were compared between disease (asthma and COPD) and medication (once and twice daily) cohorts. Minimal significance for group differences: P≤0.05.ResultsAmong 100 patients, 93% received communication from their doctor or nurse about the switch and 73% received training on using the new inhaler. Patients used their new treatment for an average of 7 months prior to completing the survey. Patient satisfaction with the new therapy was high (PASAPQ; mean overall satisfaction: 6.2 for asthma; 6.0 for COPD; P=0.338). However, asthma was not well controlled (ACQ-6) in 62% of patients with asthma, and 56% of patients with COPD reported high/very high impact of their illness on their lives (CAT). Sixty-eight percent and 70% of patients with asthma and COPD, respectively, required reliever medication (≥3 puffs) most days during the week prior to the survey. There were no significant differences in disease control (ACQ-6, CAT) between once-daily and twice-daily treatments (P>0.05 for both asthma and COPD).ConclusionEven when reporting satisfaction with their new medication, objective measures showed substantial morbidity, regardless of DPI device or dosing regimen.

THU0175 REAL-WORLD EXPERIENCE OF SWITCHING FROM ORIGINATOR TO BIOSIMILAR RITUXIMAB IN RHEUMATOID ARTHRITIS

Background:Pre-clinical and trial data confirm biosimilar rituximab (RTX-B) has equivalent physicochemical properties, function, efficacy and safety as originator (RTX-O)1,2. However, real-world data are lacking, including non-medical switch to RTX-B in patients established on RTX-O. Loss of response (LOR) has been observed following open-label switch to other biosimilars3, and it is unclear how patients who develop LOR after switching should be managed.Objectives:To describe our real-world experience of non-medical switch from RTX-O to RTX-B in RA and explore treatment strategies for patients developing LOR to RTX-B (switch back to RTX-O versus other b/tsDMARDs).Methods:We conducted a retrospective observational study of RTX-treated RA patients in Leeds from May 2002–Jan 2020. From Oct 2017, all patients on RTX-O were switched to RTX-B unless specified by treating clinician or informed consent not obtained. Demographic and clinical data were collected from electronic health records. Effectiveness was assessed by DAS28-CRP and RTX retention (using Kaplan-Meier method). Changes in treatment were based on clinician judgment.Results:944 patients with RA received ≥1 cycle of RTX in Leeds over the past 17 years. Of these, 358 required RTX re-treatment during the study period (Oct 2017–Jan 2020); 263 (73.5%) switched to RTX-B, whilst 95 (26.5%) remained on RTX-O (medical reason=46.3%; patient decision=53.7%). 256/263 patients on RTX-B with 4-month data were analysed. 201/256 (78.5%) were female, mean (SD) age 63.1 (12.4), 97.7% seropositive, 81.6% on csDMARD (62.9% methotrexate), 14.8% oral steroid, 58.6% had previous bDMARDs, and mean (SD) RTX-O cycles pre-switch was 6 (3.6). Total follow-up was 378 patient-years. Mean (SD) DAS28-CRP was 3.01 (1.17) 4 months post-last cycle RTX-O and 3.32 (1.31) post-switch to RTX-B (mean diff +0.30, 95% CI 0.004-0.60; p=0.047), with increase in VAS (+5.7, 95% CI 0.09-11.37; p=0.047), but not SJC, TJC or CRP. At last follow-up, 185/256 (72.3%) patients remained on RTX-B [median (range) RTX-B cycles 2 (1-4)]. RTX-B retention rate estimates were 79.4% and 71.3% at 12 and 18 months respectively. Following RTX-B discontinuation, 33/256 patients (12.8%) switched back to RTX-O [LOR=30 (11.7%), adverse effects (AEs)=3 (1.2%)], 13/256 (5.1%) started other b/tsDMARDs, and 25/256 (9.7%) stopped treatment (no longer indicated=7, deaths=7, loss to follow-up=6, patient choice=3, new contraindication=2). Of 46 patients with LOR/AE to RTX-B, 39 discontinued after cycle 1 (C1), 5 after C2 and 2 after C3. 31/33 patients switched back to RTX-O remained on treatment but follow-up was limited [mean (SD) 7.5 (5.2) months; 23/33 had 1 cycle only]. Compared with patients treated with other b/tsDMARDs, those switched back to RTX-O had more previous RTX-O cycles [mean (SD) 6.67 (3.28) versus 2.62 (2.10); p<0.0001]. Compared with patients who remained on RTX-B (n=185), those who discontinued for LOR/AE/death (n=53) had more previous bDMARDs (mean 1.26 vs 0.83; difference 0.43, 95% CI 0.10-0.77, p=0.01), but no differences in other clinical characteristics, treatment or B-cell numbers.Conclusion:Our real-world single-centre experience of non-medical switch from RTX-O to RTX-B in RA showed approx. three quarters of patients remained on RTX-B and maintained stable disease activity. However, apparent LOR occurred in 16%. Of >10% switched back to RTX-O, the majority remained on treatment at short-term follow-up.

Communication of Medication Nonmedical Switching Policies and Procedures by Insurance Companies: Results of an E-Survey

PurposeNonmedical switching is defined as a change in a stable patient's prescribed medication to a clinically distinct, nongeneric alternative for reasons other than lack of clinical response, adverse effects, or poor adherence. Nonmedical switching often results from formulary changes implemented by insurers to lower medication costs. We sought to survey randomly sampled physicians to elicit their opinions regarding insurers' communication about nonmedical switching. MethodsWe performed an online, cross-sectional survey of licensed, practicing physicians who were >2 years but <30 years out of residency and/or fellowship, who practiced in an internal medicine, family medicine, or specialist setting, spent ≥10% of their work time providing direct patient care, and had received at least 1 request for a nonmedical switch for ≥1 patient in the prior 12 months. The survey was fielded from November to December 2018. We report weighted percent responses categorized from 5- or 7-point Likert scale questions. FindingsE-mail invitations were sent to 13,117 randomly sampled physicians, and 1818 opened the e-mail and followed the embedded survey link to participate. Of these, 1010 total physicians (55.5%), 606 primary care and 404 specialists, who treated patients experiencing nonmedical switching in the prior 12 months completed the survey. A few physicians were notified about nonmedical switches by insurers; more frequently physicians learned about them from pharmacies serving their patients. Notification frequently occurred at or after a refill came due. Notification via electronic medical record or insurer letter was less frequent. Few thought that insurers clearly communicated information about alternative medications when a nonmedical switch was required, and most disagreed that insurers provided clear procedures, timelines, and methods to track challenges. Nearly all agreed that insurers should provide supporting documentation or rationale for nonmedical switches and specifics on alternatives. Respondents overwhelmingly agreed that steps to improve communication and physicians' and patients’ ability to navigate nonmedical switches or challenge procedures should be implemented. ImplicationsThis survey of primary care and speciality physicians suggests that physicians believe that insurers’ current level of communication regarding nonmedical switching is suboptimal. Respondents suggested that insurers did not optimally communicate information about alternative medications when a nonmedical switch was required and did not provide clear procedures, timelines, and methods to track challenges. A preponderance of physicians agreed that steps to improve physician-insurer communication to aid in the navigation of nonmedical switch and to challenge procedures should be implemented. If not addressed, these identified nonmedical switch communication issues may have a negative effect on achieving the quadruple aim of enhancing patient experience, improving population health, reducing costs, and improving the work life of health care practitioners and their staff.

Outcomes of a drug shortage requiring switching in patients with ulcerative colitis.

BACKGROUNDDrug shortages are common yet their impact on patient care and their commercial ramifications has not been adequately researched. In Australia a shortage of balsalazide (2012-2013) necessitated substitution with alternative 5-aminosalicylate (5-ASA) formulations for ulcerative colitis (UC).AIMTo assess and compare the clinical and commercial sequelae of non-medical switching from balsalazide to another 5-ASA and/or return to balsalazide once supply resumed.METHODSA prospective cohort study of patients on balsalazide for mild-moderate UC was conducted where, strictly due to the national shortage (November 2012- January 2013), were switched to alternative 5-ASA and/or then returned to balsalazide once supply resumed. Clinical (Partial Mayo), endoscopic (Mayo score) activity, adverse effects (to alternative 5-ASA) and percentage market share (of continuous 5-ASA users) from baseline (i.e., time of switching due to shortage) through to five years were assessed.RESULTSOf 31 patients switched due to the shortage, 12 (38.7%) resumed balsalazide immediately once supply resumed, 8 (25.8%) prompted by adverse effects to the alternative 5-ASA used. Three patients (9.7%) had documented symptomatic improvement, 15 (48.4%) were unchanged and 13 (41.9%) had symptomatic worsening vs baseline (P < 0.01), after switching to an alternative 5-ASA. At 3 and 5y post switch, overall 26/31 (83.9%) and 23/31 (74.2%) had remained continuously on any 5-ASA therapy respectively. Twelve (38.7%) and 11 (35.5%) patients remained on balsalazide continuously at three and five years respectively after drug supply returned, equating to a loss of market share (within 5-ASA class) of 45.2% and 38.7% respectively.CONCLUSIONThis study of a balsalazide shortage in UC patients exemplifies the detrimental impact of a drug shortage on long term patient, disease and commercial outcomes.

P12 Clinical responses, B cell depletion and treatment outcomes following rituximab biosimilar switch in RA: is there value in switching back?

Abstract Background There has been a national cost-saving drive to switch from originator rituximab (RTX-O) to biosimilar (RTX-B). Whilst regulatory clinical trials necessitate demonstration of equivalence, subtle physicochemical changes could theoretically alter function, safety and efficacy. Some uncertainty remains amongst clinicians and patients, and real-world studies of non-medical biosimilar switching demonstrate clinically relevant discontinuation rates. Here we present our descriptive experience of switching to RTX-B in rheumatoid arthritis (RA), with a focus on B-cell depletion and inadequate responders (IR) subsequently switched back to RTX-O. Methods RA patients in Leeds were switched from RTX-O to RTX-B. Routine clinical data were collated, including baseline characteristics, previous treatment, clinical responses, initial B cell depletion (BCD) by high sensitivity flow cytometry, treatment outcomes. For switch back patients, responses were characterised according to DAS28, EULAR response, and association with BCD. Results 263 RA patients in total switched to RTX-B. After 1st cycle RTX-B (excluding missing data), 180/241 (74.7%) had clinical response, 213/261 (81.6%) had complete BCD. Subsequent treatment outcomes were as follows: 140/263 (53.2%) re-treated with RTX-B, 57 (21.7%) awaiting re-treatment with RTX-B, 27 (10.3%) switched back to RTX-O for IR, 4 (1.5%) switched back for adverse events, 11 (4.2%) switched to another biologic, 24 (9.1%) treatment discontinued. Response data are currently available for 19/27 RTX-B-IR patients switched back to RTX-O (16/19 female, mean age 66.8, mean RTX cycles 6.7, 14/19 on DMARD, 11/19 osteoarthritis). Regarding RTX-B response, 3 had missing data, 2/16 (12.5%) had good response when EULAR criteria applied (but reduced duration), 4/16 (25%) moderate response (but subjectively poor), 10/16 (62.5%) non-response. Of available data in 10/19 after subsequent RTX-O (9 awaited/missing), 5/10 had EULAR good response, 2/10 moderate, 3/10 non-response. BCD occurred in 13/19 (68.4%) with RTX-B, 17/19 (89.5%) with subsequent RTX-O. All 5 good responders following switch back had EULAR non-response to RTX-B and complete BCD pre/post switch. Interestingly, of a further 19 RTX-B treated patients with incomplete BCD but not switched back, 15/19 had complete depletion with subsequent RTX-B. Of the 4 adverse events, 2 had infusion reactions (1 successfully re-treated with RTX-O, 1 pending), 1 headaches (resolved with RTX-O), 1 worsening hearing loss (likely unrelated). Conclusion Some patients with IR to RTX-B had good response after switching back to RTX-O. BCD was not predictive of this response. After incomplete BCD with RTX-B, most subsequently depleted with either RTX-O or RTX-B. RTX-B adverse events were rare; some resolved with RTX-O. Assessment of response in this context is challenging; DAS28 may be less clinically relevant with RTX when aiming to re-treat before flares, and discrepancies arise between DAS28 and subjective responses (e.g., influenced by longstanding disease/treatment, concurrent osteoarthritis, ‘nocebo’ effect). This real-world clinical service evaluation has its limitations; data collection is ongoing. Disclosures A. Melville None. M. Buch Honoraria; Abbvie, Astra Zeneca, BMS, Lilly, Roche, Sandoz, UCB. J. Nam None. P. Emery Consultancies; BMS, AbbVie, Pfizer, MSD, Novartis, Roche, UCB. Grants/research support; AbbVie, BMS, Pfizer, MSD, Roche. Other; Undertaken clinical trials and provided expert advice to Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly. B. Saleem Other; Speaker fees (Sanofi). S. Dass Consultancies; Roche. Honoraria; Roche. Other; Speaker fees (Roche).

Effects of successive switches to different biosimilars infliximab on immunogenicity in chronic inflammatory diseases in daily clinical practice

ObjectiveTo evaluatre the risk of immunogenicity in patients with chronic inflammatory diseases who experienced successive non-medical swiches to different biosimilars infliximab. Patients and MethodsObservational study over a 3-year observation period assessing the risk of immunogenicity in i) patients in maintenance therapy with innovator infliximab who were successively switched to CT-P13, then to SB2 (cohort-1) and ii) biologic-naive patients initiated with CT-P13 before being switched to SB2 (cohort-2). A propotion meta-analysis was also performed, integrating our results to 16 additional studies. ResultsCohort-1 included 265 patients who switched to CT-P13, and 140 patients were subsequently switched to SB2. Among the 235 anti-drug antibody (ADA)-free patients at baseline, 20 patients (8.5%) developed ADA over the 3-year observation period (rate of 3 for 100 patient years). Cohort-2 included 44 patients, of whom 29 subsequently switched to SB2. A total of 11 patients (25%) developed ADA within 3 years (rate of 14 for 100 patients years). We found no influence of the number of biosimilars infliximab received on ADA deveopment in both cohorts. The risk of treatment discontinuation was significantly higher in patients with positive ADA in both cohorts. The meta-analysis including our data exposed an incidence of immunogenicity of 4.7% (95% CI 3.5–6.1%) after the switch from innovator infliximab to biosimilar infliximab and 21.1% (95% CI 13.1–30.3%) in patients initiating biosimilar infliximab. ConclusionImmunogenicity was not favored by successive non-medical switches to biosimilars infliximab in our study, but was associated with treatment discontinuation.

The Argument Against a Biosimilar Switch Policy for Infliximab in Patients with Inflammatory Bowel Disease Living in Alberta.

A nonmedical switch policy is currently being considered in Alberta, which would force patients on originator biologics to biosimilar alternatives with the hypothetical aim of reducing costs to the health care system. The evidence to support the safety of nonmedical switching in patients with inflammatory bowel disease (IBD) is of low to very low quality; in fact, existing data suggest a potential risk of harm. In a pooled analysis of randomized controlled trials, one patient would lose response to infliximab for every 11 patients undergoing nonmedical switching. Switching to a biosimilar has important logistical and ethical implications including potential forced treatment changes without appropriate patient consent and unfairly penalizing patients living in rural areas and those without private drug insurance. Even in the best-case scenario, assuming perfectly executed switching without logistical delays, we predict switching 2,000 patients with Remicade will lead to over 60 avoidable surgeries in Alberta. Furthermore, nonmedical switching has not been adequately studied in vulnerable populations such as children, pregnant women, and elderly patients. While the crux of the argument for nonmedical switching is cost savings, biosimilar switching may not be cost effective: Particularly when originator therapies are being offered at the same price as biosimilars. Canadian patients with IBD have been surveyed, and their response is clear: They are not in support of nonmedical switching. Policies that directly influence patient health need to consider patient perspectives. Solutions to improve cost efficiency in health care exist but open, transparent collaboration between all involved stakeholders is required.

Systematic Review: Non-medical Switching of Infliximab to CT-P13 in Inflammatory Bowel Disease

Background and AimsBiosimilar approval, such as Inflectra™ (CT-P13) for treating ulcerative colitis (UC) and Crohn’s disease (CD), has reduced direct drug costs. Though clinicians are comfortable with biosimilar use in treatment-naïve patients, there are concerns in some jurisdictions that there are insufficient data from well-controlled trials to support non-medical switching. A systematic review, along with a critical assessment of the study design, was conducted to assess the potential impact of switching stable CD/UC patients from infliximab to CT-P13.MethodsA literature search using PubMed and abstracts/posters from 3 major gastroenterology conferences from 2014 to 2018 was completed. Two individual reviewers extracted data from each relevant report and compiled it into evidence tables to facilitate descriptive analyses. Key randomized trial and observational study designs were critically assessed to contextualize data relevance.ResultsA total of 49 reports (3 randomized controlled trials, 40 observational trials, and 1 case series) were included. Most studies revealed no efficacy, safety, or immunogenicity concerns with non-medical switch. Limitations of supporting data include a small number of randomized controlled trials; predominance of observational studies with varying outcome assessments and lack of appropriate controls; and scarcity of research on biosimilar switch long-term effects.ConclusionsThe majority of studies suggested non-medical switch is safe. However, clinicians and regulatory bodies should be aware of differences and limitations in study designs when making inferences about the risks and benefits of switching stable IBD patients to biosimilars.

Nonmedical Switching From Originators to Biosimilars: Does the Nocebo Effect Explain Treatment Failures and Adverse Events in Rheumatology and Gastroenterology?

The act of nonmedical switching, defined as switching stable patients who are generally doing well with their current therapy from an originator biologic to its biosimilar, has been endorsed as a reasonable treatment strategy. The safety and efficacy of nonmedical switching have been evaluated in randomized controlled and real-world evidence studies, which have demonstrated that although many patients maintain treatment response after the switch, some patients experience therapy failure, resulting in therapy discontinuation. It has been postulated that the vast majority, if not all, of these treatment failures result from a “nocebo effect”, defined as patients’ negative expectations toward the therapy change. Reports suggest that the risk of a nocebo effect is higher following a mandated nonmedical switch. Although the nocebo effect is a well-recognized phenomenon in pain studies, evidence is limited in immune-mediated diseases primarily because it is difficult to quantify, especially retrospectively. In spite of this, numerous biosimilar studies in patients with immune-mediated diseases have concluded that nonmedical switching failures are due to a nocebo effect. The objective of this narrative review was to explore the reasons for nonmedical switch failure or discontinuation and the role of the nocebo effect among patients with inflammatory rheumatic and gastrointestinal diseases who switched from an originator biologic to its biosimilar.

P505 Different failure rates after non-medical switching of 744 patients from adalimumab originator to 2 different adalimumab biosimilars at Cambridge University Hospitals, UK: real-world experience

Abstract Background Biosimilar adalimumab became available in the UK in October 2018, with payers introducing a series of measures to drive the adoption of the ‘best value’ adalimumab.1 Consideration of value should include risk of loss of efficacy and adverse reactions, which might drive further biologic switches or ‘reverse switches’ to originator. Managing potential ‘nocebo effect’ requires high levels of patient engagement, whilst the presence or absence of citrate buffer may affect patient-reported discomfort, hence patient treatment perceptions. Methods Patients were switched to 2 different biosimilar adalimumabs, one buffered with citrate (ADA1) and one in a citrate-free buffer (ADA2). The choice of adalimumab biosimilar was made for clinical and economic reasons. Patients were informed of the switch to either ADA1 or ADA2 in advance via letter and at clinic visits. Patients who reported problems after switching were reviewed. Results A total of 744 patients were switched from originator adalimumab (ADA0) to ADA1 or ADA2. Rheumatology and dermatology patients were switched to ADA1, whilst gastroenterology patients were switched to ADA2, except for those with a latex allergy, where ADA1 was used (or ADA2 in a latex-free syringe). A total of 49 (6.6%) patients reported problems and a further switch of drug was judged necessary in 48 (Table 1). Switch failure was significantly more likely with ADA1 than ADA2 (7.7% vs. 1.8%; p = 0.006). The median time to switch failure was 97 days (range 5–196 days). The commonest reason for switch failure was disease flare (23 patients, 48%), followed by injection site pain or reaction (21 patients, 44%). Disease flare and injection site problems were more likely to be reported with ADA1 than ADA2 (flare: 23/583 vs. 0/161, p = 0.008; injection site pain 20/583 vs. 1/161, p = 0.06). For patients reporting disease flare, clinicians tended to select a reverse switch to ADA0, whilst for those with injection site problems, a further switch to a different biosimilar was the preferred approach; both strategies were effective at recapture. Conclusion In the context of an effective patient communication strategy, adalimumab biosimilar switching was associated with overall low rates of patient-reported problems in a large cohort. Despite an identical communication strategy, significantly higher rates of injection site problems and disease flares were seen between 2 different biosimilars, reflected in a higher need for further switches. These differences may impact the cost-effectiveness of any chosen strategy. Reference

Physicians' perspectives regarding non-medical switching of prescription medications: Results of an internet e-survey.

BackgroundPhysicians are in an ideal position to describe the impact of medication non-medical switching (switching commonly due to formulary changes by insurer for reasons unrelated to patient health) on their practice dynamics and patient care. We sought to examine physicians’ openness to requests for non-medical switching and their experiences and opinions regarding the impact of non-medical switching on their practice, staff and patients.MethodsAn online survey of randomly-sampled physicians spending ≥10% of time providing patient care and having received ≥1 non-medical switch request during the prior 12-months. The impact of non-medical switching on clinical decision-making process; professional experience with clinical practice, patient-physician relationship, insurance process; and perceived impact on practice, staff and patients were assessed. Weighted percent responses were calculated.ResultsWe sampled 1,010 physicians (response rate = 55.5%). Many responded being frequently not amenable (26.0%) or had reservations (41.8%) to non-medical switch requests; with >50% indicating patient stability on current therapy and suboptimal alternatives as factors frequently influencing amenability. Physicians agreed non-medical switching can create ethical concerns (clinical judgement, autonomy, ability to treat per guidelines; 74.8%, 82.3%, 53.5%, respectively), while forcing them to take responsibility for insurers’ decisions (81.1%) and diverting their clinical time (84.3%). Most indicated non-medical switching increased practice burden (administrative, non-billable interactions, additional staffing, non-office patient contact, calls to/from the pharmacy; 85.0%, 72.5%, 62.2%, 64.2%, 69.5%, respectively). Physicians felt insurer processes discouraged non-medical switch challenges (76.7%) and required inconvenient lengths-of-time (76.1%) speaking to insurer representatives without proper expertise (62.0%). They believed non-medical switching negatively impacted aspects of care (effectiveness, side-effects, medication adherence and abandonment, out-of-pocket costs, medication errors; 46.5%, 53.2%, 50.6%, 49.4%, 59.6%, 54.5%, respectively).ConclusionsPhysicians were frequently not amenable or had reservations regarding non-medical switching. They noted ethical concerns due to non-medical switching. Most felt non-medical switches burdened their practice and negatively impacted care.

The Law and Ethics of Switching from Biologic to Biosimilar in Canada.

Governments and financial institutions in several jurisdictions are planning or implementing nonmedical/‘forced’ switches by cutting drug coverage for reference biologics and funding only less expensive biosimilars. Switches raise numerous ethical and legal challenges, as the drugs are framed as not being identical and, despite strong evidence for noninferiority of some biosimilars, there is controversy over whether switching can sometimes lead to adverse events. Canadian law generally requires physicians to give precedence to their patients’ best interests over social interests such as cost containment. The primacy of patients’ interests is also clearly reflected in professional policies and codes of ethics. Moreover, physicians are obligated to disclose everything a reasonable person in the patient’s position would want to know when obtaining informed consent for treatment, including addressing not only scientific information but also relevant social controversy about nonmedical switches. Under Canadian law, physicians may be obligated to tell patients about the ability to access unfunded biologics, even if patients lack the resources to obtain them. In sum, while there is no inherent right to funding for reference biologics in Canada, physicians in some circumstances may have a legal obligation as fiduciaries to advocate on behalf of patients to remain on a reference biologic. At a minimum, the controversy surrounding switching will necessitate, as part of the consent process, a robust and thorough disclosure of relevant risks, benefits and reasonable alternatives.

Specialist physician perspectives on non-medical switching of prescription medications

ABSTRACT Introduction: A non-medical switch is a change to a patient’s medication regimen for reasons other than lack of clinical response, side-effects or poor adherence. Specialist physicians treat complex patients who may be vulnerable to non-medical switching. Objectives: To evaluate specialist physicians’ perceptions regarding the frequency of non-medical switch requests, and the impact on their patients’ outcomes and healthcare utilization. Methods: An online survey of randomly sampled physicians spending ≥10% of time providing patient care and having received ≥1 non-medical switch request during the prior 12-months. Results: Among 404 specialist physicians surveyed, non-medical switch requests were reported as very frequent or frequent by 35.0% of oncologists (for injectable cancer agents) and up to 80.3% of endocrinologists (for injectable anti-hyperglycemics). Respondents reported decreased medication effectiveness (25.0% of oncologists to 75.0% of dermatologists) and increased side-effects (32.5% of oncologists to 66.7% of psychiatrists). Most specialists reported very frequent or frequent increases in non-office visits (52.5% of oncologists to 75.3% of endocrinologists) and calls with pharmacies (57.5% of oncologists to 80.5% of rheumatologists) due to non-medical switching. Conclusions: Receipt of non-medical switching requests were common among specialist physicians. Non-medical switching may lead to negative effects on patient care and require increased healthcare utilization.

Effectiveness and safety of switching to adalimumab biosimilar ABP 501 in Crohn's disease: the extrapolation concept.

We sincerely thank Viscido et al. for their appropriate and sharable comments on our recent study on adalimumab biosimilar ABP 501 in Crohn's disease (CD). The use of a biosimilar in inflammatory disorders is one of the current main topics, given the great opportunity to save resources that can be invested in innovative drugs and the ethical problems that non-medical switching can generate.

Overcoming barriers to biosimilars in inflammatory arthritis.

The availability of biosimilars to treat inflammatory diseases has generated concern about changing patients from a bio-originator to its biosimilar to save costs. Studies published in 2019 support the effectiveness and safety of ‘nonmedical switching’ and highlight the benefits of communicating information about biosimilars to patients in a positive light.

Same but different? A thematic analysis on adalimumab biosimilar switching among patients with juvenile idiopathic arthritis

BackgroundBiologic medications have dramatically enhanced the treatment of many chronic paediatric inflammatory conditions. Their high cost is a factor that prohibits their broader use. Cheaper generic versions, or biosimilars, are increasingly being used. Healthcare services are switching some patients over to biosimilars for economic reasons, known as ‘non-medical switching’. Some patients unsuccessfully switch due to perceived decreases in efficacy or non-specific drug effects. The implications of failed switching include exhaustion of therapeutic options, unnecessary exposure to other medications, increased healthcare utilisation, worse patient outcomes and higher overall healthcare costs. Patient perceptions almost certainly play a role in these ‘failed switches’.MethodsA thematic analysis was performed to better understand patient and parent perceptions on non-medical biosimilar switching. The study was conducted in accordance with the Consolidated Criteria for Reporting Qualitative Research recommendations. Patients with juvenile idiopathic arthritis currently taking adalimumab were included.ResultsNine families were interviewed just prior to a hospital trust-wide non-medical switch to an adalimumab biosimilar. Several common themes were identified. The most frequent concerns were regarding practical aspects of the switch including the medication administration device type; the colour of the medication and administration device; and whether the injections would sting more. The relative safety and efficacy of the biosimilar was raised although most families felt that there would be no significant difference. Anxieties about the switch were largely placated by reassurances from the medical team.ConclusionsWe derived recommendations based on existing adult literature and the observations from our study to optimise the benefits from non-medical biosimilar switching.