Switched Back Research Articles

P43 Patient tolerability of adalimumab biosimilar therapy in dermatology and rheumatology: real-world experience from a large tertiary centre

Abstract Adalimumab is widely used in the treatment of immune-mediated inflammatory diseases. It is the highest-spend drug in the National Health Service, costing more than £400 million annually. In 2018, adalimumab biosimilars became available, leading to substantial cost savings. However, patient tolerability of biosimilars remains underexplored. We evaluated the tolerability of adalimumab biosimilar therapy (Idacio®) in patients who were switched from Humira® in a large dermatology and rheumatology tertiary centre. We identified all patients issued with a prescription of Humira by dermatology [psoriasis and hidradenitis suppurativa (HS)] or rheumatology (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and Behçet disease) and analysed the number who switched to Idacio between January 2021 and March 2022. Patient electronic records were reviewed up to October 2022 to identify patients who switched back to the originator product and the documented reason for the switch. The primary outcome was the numbers of patients who were switched back from the biosimilar to the originator product. Of 769 patients issued with a prescription of Humira, 694 were switched to Idacio during the study period. Of these, 134 (19.3%) switched back to the originator product, 102 of whom (76.1%) remained on this during follow-up. The highest proportion of individuals switching back to the originator product was observed in the HS population (26.7%). The most common reasons for switching back were patient-reported loss of disease control (n = 63; 47.0%), injection pain (n = 51; 38.1%) or both (n = 10; 7.5%). The median time to switch back was 197 days (interquartile range 138–280). Of 694 patients prescribed Idacio, 32 (4.6%) were switched to an alternative biologic agent during the study period. Our experience with previous biosimilar switches within rheumatology and dermatology (etanercept, rituximab and infliximab) has resulted in few patients requiring a switch back to the originator. Our data indicate that around one in five patients in our study population switched back to the originator product. The higher proportion of patients citing injection pain may relate to the citrate excipient content or larger injection volume of the biosimilar Idacio. Loss of efficacy with time is well established with adalimumab, in part due to antidrug antibodies, and cannot be specifically attributed to the biosimilar. Switching may alter a patient’s confidence in the drug, which is particularly important when it may be a first-line therapy or the only approved biologic for a condition. Data on switch-back rates for other adalimumab biosimilars is required to understand how generalizable our findings are and the potential economic implications.

P010 Real world experience of switching to an adalimumab biosimilar; different outcomes for axial spondylitis, psoriatic and rheumatoid arthritis

Abstract Background/Aims Adalimumab is licenced to treat a variety of autoimmune conditions including inflammatory arthropathies. Switching stable patients from the bio-originator Humira to biosimilars has been strongly promoted on economic grounds and presumed equitable interchangeability regarding efficacy and tolerance across all disease indications. Our aims were to assess adalimumab biosimilar retention rates up to 1 year in patients with axial spondylitis (AS), psoriatic (PsA) and rheumatoid arthritis (RA) in a routine care setting and to determine by disease subtype reasons for switching back to Humira. Methods Retrospective observational study, utilising data from the St. George’s Hospital Rheumatology Biologics Database. Demographic details, retention duration and reasons for discontinuation for all patients switched from Humira to an adalimumab biosimilar were recorded up to 1 year. Results 238 patients (female 54.5%) were switched from Humira to an adalimumab biosimilar: AS n = 95, PsA n = 82, RA n = 61. Overall, 53% patients switched back to Humira over a 1-year period, female 57%. By disease subtype, the biosimilar retention rate at 1 year was AS 36%, PsA 61%, RA 46%. Overall, the reason for switching back to Humira was an adverse effect or device specific problem (AE) in 59% and loss of efficacy (IR) in 41%. AEs in 98% were pain and other injection site reactions. By disease subtype, the reason for switching back was: AS 59% IR, 41% AE, PsA 22% IR, 78% AE, RA 27% IR, 73% AE. Conclusion Projected cost savings from the adalimumab biosimilar switch programme were not achieved, with 53% returning to Humira up to 1 year later. By disease indication patients with AS had the lowest retention on the biosimilar, in whom loss of efficacy was more likely than an AE to trigger the switch, and over twice as prevalent than in patients with RA and PsA. AEs were the most prevalent reason for PsA and RA patients to switch back, and citrate in the biosimilar buffer solution was the likely reason for this. The loss of efficacy, particularly prevalent in AS patients, implies that equitable interchangeability between Humira and biosimilar products cannot be assumed, and projected cost saving advantages may be overestimated. Disclosure F.A.A. Holden: None. D. Hill: None. P. Kiely: None.

Dissociation of hypertension and renal damage after cessation of high salt diet in Dahl rats

BackgroundEvery year, thousands of hypertensive patients reduce salt consumption in the efforts to control blood pressure. Most of the studies agreed that about one‐third of the patients had an excellent response, one‐third had only a modest response, and one‐third had little or no response. Irreversibility of high blood pressure is associated with various mechanisms underlying the self‐sustaining character of hypertension. We hypothesize that chronic hypertension leads to sustained renal damage and excessive sodium reabsorption, staying even after removing the trigger, caused the initial blood pressure raise.MethodsWe used Dahl salt‐sensitive rats for chronic continuous observation of blood pressure with radiotelemetry in conscious free moving animals. Rats were fed a 4%NaCl diet to induce hypertension, and then the diet was switched back to normal (0.4%NaCl).Patch‐clamp analysis was performed in freshly isolated, split‐open cortical collecting ducts to characterize activity of epithelial sodium channel (ENaC), responsible for sodium reabsorption in aldosterone‐sensitive distal nephron. Flow cytometry, trichrome staining and FITC‐inulin clearance estimated immune cell infiltration, renal damage and renal function.ResultsWe found that blood pressure increase is reversible if induced by a short 3‐day long feeding with 4%NaCl diet. A 3‐week long high salt diet develops a sustaining hypertension (MAP ~150 mmHg): switching back to 0.4%NaCl diet slightly reduces blood pressure (to 145 mmHg) next day, but later hypertension progresses, reaching ~158 mmHg. Notably, the self‐sustaining phase of hypertension was sensitive to benzamil treatment, which lowered BP to ~136 mmHg.Patch clamp analysis revealed that development of hypertension was accompanied with elevated ENaC activity which also stayed high, despite withdrawal of 4%NaCl diet.A separate subset of experiments demonstrated that dietary salt reduction in hypertensive animals decreases the number of total CD45+CD3+CD4+ and CD45+CD3+CD8+ cells in renal tissues.Also, we found a reduced area of protein casts abundance in the post‐salt hypertensive group in comparison with age‐matched rats kept on a high salt diet, and improving a glomerular filtration rate in the post‐salt period.ConclusionBased on our earlier publications and current data, we conclude that ENaC activity contributes to both development of salt‐sensitive hypertension and its continuation in the absence of high salt challenge. However, dietary salt restriction reduces renal inflammation and damage in hypertensive animals.

Validation of a Novel Forecasting Method for Estimating the Impact of Switching Pneumococcal Conjugate Programs: Evidence from Belgium.

IntroductionSince 2010, 10-valent (PCV10) and 13-valent pneumococcal conjugate vaccines (PCV13) have been available as part of infant national immunization programs. Belgium is as one of the few countries that implemented PCV13 (2007–2015), switched to PCV10 (2015–2018) and then switched back to PCV13 (2018–present) after observing increases in disease. We assessed the impacts of both historical and prospective PCV choice in the context of the Belgian health care system and used this experience to validate previously developed economic models.MethodsUsing historical incidence (2007–2018) of pneumococcal disease for Belgian children aged < 16 years, observed invasive pneumococcal disease (IPD) trends from surveillance data were used to estimate future disease in a given PCV13- or PCV10-based program. We compared observed incidence data with two modeled scenarios: (1) the 2015 switch to PCV10 and (2) a hypothetical continuation of PCV13 in 2015. Finally, we explored the potential impact of PCV choice from 2019 to 2023 by comparing three scenarios: (3) continued use of PCV10; (4) a switch back to PCV13; (5) a hypothetical scenario in which Belgium never switched from PCV13.ResultsModel predictions underestimated observed data from 2015 to 2018 by 100 IPD cases among ages < 16 years. Comparing observed data with scenario 2 suggests that PCV13 would have prevented 105 IPD cases from 2015 to 2018 compared with PCV10. Switching to PCV13 in 2019 would avert 625 IPD cases through 2023 compared with continuing PCV10. Scenario never switching from PCV13 would have resulted in a reduction of 204 cases from 2016 to 2023 compared with switching to PCV10 and switching back to PCV13.ConclusionThe findings from this study suggest that previously published modeling results of PCV13 versus PCV10 in other countries may have underestimated the benefit of PCV13. These results highlight the importance of continually protecting against vaccine-preventable pneumococcal serotypes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00485-9.

From a DOAC to Warfarin: Reasons Why Patients Switch

1. IntroductionThe introduction of direct oral anticoagulants (DOACs) has led to their widespread use for stroke prevention in patients with non-valvular atrial fibrillation (AF) and as first-line treatment in acute venous thromboembolism (VTE), and also as secondary thromboprophylaxis in patients with a history of VTE. In addition, many patients previously taking vitamin K antagonists (VKAs) have switched to a DOAC for reasons including erratic international normalised ratio (INR) control, medication interactions, convenience, possible lower major bleeding risk and possible improved stroke prevention rates. Although DOACs are well tolerated, little is known about the numbers of patients switching from a DOAC to (or back to) a VKA or the reasons for doing so.2. MethodsThis study was an analysis of prospectively-collected data from a four-year period surveying a computer-based VKA (warfarin) dose adjustment clinic in a large city centre hospital. The primary objective was to identify the reasons for patients switching from a DOAC to warfarin. Secondary objectives included assessing indication for anticoagulant therapy and choice of DOAC. The time in therapeutic range (TTR) once switched back to VKA and clinical events following commencement of warfarin were also determined.3. ResultsIn our VKA clinic with 1791 patients annually under review, 39 patients were identified as having switched from a DOAC to warfarin. The mean age of the patients was 68.5 years +/- 13.8 and the majority (N=24) were female. AF was the most common condition necessitating anticoagulation (N=24); VTE accounted for 12 cases; arterial thromboembolism (N=2) and cardiac thrombus (N=1) were less common causes and one patient had been started on a DOAC in the setting of valvular replacement. Of the patients who were switched to warfarin, seven (17.9%) had originally been anticoagulated with a VKA prior commencing on a DOAC. In terms of anticoagulant choice, the majority of patients (N = 27) were taking rivaroxaban with 6 patients each on dabigatran and apixaban. The causes for switching in this cohort are outlined in table 1. Interesting cases of note include one patient who had a splenic infarction while taking rivaroxaban for atrial fibrillation and one patient who developed a new thumb arterial embolus while taking rivaroxaban for a PE.Following warfarin commencement, there was a total of eight clinical events reported (21.1% of patients). There were seven bleeding events recorded with two serious events necessitating hospital admission and five minor events; in five of these (71.4%), the original reason for switching back to warfarin had been a bleed while on a DOAC. One further patient had a high INR necessitating administration of vitamin K. The mean TTR of this cohort was 61.4% +/- 22.3. 33 patients (84.6%) of patients still attend the warfarin clinic, with cessation of anticoagulant therapy having occurred in three patients (7.7%) and death occurring in one patient (2.6%); two patients (5.1%) have been recommenced on a DOAC.4. DiscussionDOACs have several advantages over warfarin for many patients; they do not require monitoring and the dose remains stable. Index trials have demonstrated at least non-inferiority to warfarin in stroke prevention in non-valvular AF and treatment of VTE, with at least no significant difference in bleeding outcomes. However, warfarin can be an attractive option in complicated cases as it can be rapidly reversed, and there continues to be greater levels of clinician experience with its use. In the present study, we report data regarding the switch back to warfarin in a DOAC cohort, an area into which little research has been conducted. There were only 39 patients reported over a four-year period; this represents only a small minority of the full cohort. As expected, the majority of patients required a switch because of re-thrombosis or a bleeding event. Patients also required an appropriate switch in situations outside of the licence of the DOACs i.e. renal deterioration or valvular AF. The authors are not aware of any data regarding arterial embolisation in rivaroxaban users, and acute hepatitis has been rarely described in rivaroxaban use. These data confirm that switching from a DOAC to warfarin is seldom deemed necessary by clinicians. However, familiarity and experience may guide therapy in complicated cases, and vigilance is required to ensure adherence to the licence when prescribing a DOAC. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

AB1196 A STUDY REVIEWING THE ASSOCIATED FACTORS AND COST-EVALUATION OF SWITCHING BACK TO ORIGINATOR-ETANERCEPT FROM ITS BIOSIMILAR AMONG PATIENTS WITH RHEUMATIC DISORDERS AT A TERTIARY CARE CENTRE IN UNITED KINGDOM

Background:Biological therapy plays a major role in the management of patients with rheumatic disorders. Evidences generated at experimental settings have shown biosimilars as clinically effective, safe and cost effective. Nevertheless, real world data are lacking about cost effectiveness and causes of switching back to originator product among patientsObjectives:To describe the associated factors and cost evaluation of switching back to the originator etanercept from the biosimilar among patients with rheumatic disorders at The Robert Jones and Agnes Hunt Orthopaedic Hospital of United KingdomMethods:A descriptive cross-sectional study was undertaken with secondary data in a tertiary care hospital. All the patients who were switched from original etanercept (originator) to biosimilar Etanercept from October 2018 to June 2019 were included in the study. A pre-tested data extraction sheet was used in the data collection. Annual expenditure estimates for the treatment modalities were collected by consulting the experts. Descriptive analysis was done for the characteristics of the study sample and for the estimated annual costs. Associations of age and sex in the switching of treatment modalities were explored with chi-square test and Mann Whitney U test with 5% significance level.Results:Records of 100 participants were extracted with a male to female ratio of 1: 1.4. The median [interquartile range (IQR)] of the participants was 54 (44 to 66) years. The leading three diagnoses were: rheumatoid arthritis (65%), Ankylosing Spondylitis (18%) and Psoriatic arthritis (14%). Out of the participants, 32 (32%) switched back to originator with a median (IQR) duration of 16.0 (10.5 to 19.5) weeks of commencing the biosimilar. The proportions of switching back were 28.1%, 34.4% and 37.5% among those who did, in the chronological 3- monthly intervals of the study. The main reasons for switching back included; side effects (21.9%), lack of efficacy (65.6%), both of these (9.4%) and other reasons (3.1%). Older age was observed among those who switched back (p&lt;0.05) but gender did not show a statistically significant association (p=0.532). The annual estimated cost for biosimilar was 37.3% less than that for originator per patient.Conclusion:In our cohort nearly one third switched back to the originator following the commencement of biosimilar incurring a financial and resource burden to the rheumatology department which in turn will have wider ramifications on the health care system. Exploring the reasons and factors associated with switching back to the originator in larger scale studies would help in planning cost-effective interventions and understanding the reasons why the patients revert back to the originator from the biosimilar therapy, especially among the older patients.

AB1343-HPR A QUALITATIVE REVIEW ASSESSING THEMATIC OUTCOMES FROM THE PHARMACY-LED ADALIMUMAB BIOSIMILAR SWITCH PLAN ACROSS 3 SPECIALITIES; RHEUMATOLOGY, GASTROENTEROLOGY AND DERMATOLOGY AT UNIVERSITY HOSPITALS OF COVENTRY AND WARWICKSHIRE (UHCW)

Background:The advent of biosimilars has heralded a new era for cost effective biologic prescribing in the NHS. As patents expire for originator biologics, less expensive versions are now widely available as biosimilars. Non-medical switches (for reasons unrelated to a patient’s health) ensure prescribing of best value medicines, and cost savings can be redirected to patient care.1This practice resonates with recommendations from Lord Carter’s 2016 report regarding reducing unwarranted variation in the NHS and adopting cost saving opportunities.2In 2018/19, following loss of patent exclusivity for the expensive adalimumab originator biologic, UHCW worked in accordance with national directives to drive forward one of the largest non-medical biosimilar switches.Objectives:This qualitative review aims to explore the success of the adalimumab biosimilar switch and key themes associated with switch backs/refusals across the Rheumatology (R), Gastroenterology (G) and Dermatology (D) specialities at UHCW.Methods:The switch plan occurred between April-December 2019. 403 patients (R;189, G;176, D; 38) were eligible for switch. Patients were informed of the plan in advance via a patient information leaflet/hospital clinic visits. Switch refusals, withheld treatments and cancellations were documented and patients were advised to contact the hospital pharmacy/clinical teams if they encountered any concerns, adverse effects or lack of efficacy post switch. The clinician would then advise on subsequent management.Results:During April-December 2019, 264/403 patients had been successfully switched (R;122, G;109, D;33). 33/403 patients switched back to the originator biologic (R;22, G;10; D;1). Of the 22 rheumatology switch back patients; 6 patients reported injection site pain and variably headache, fatigue, disease relapse, gastrointestinal (GI) upset, erythema; 10=reported lack of efficacy and variably influenza-type symptoms, relapse in associated psoriasis, difficulty in walking/sleeping, hair loss, excessive perspiration, facial cellulitis, foot drop and GI upset; 1=blepharitis;1=latex allergy before injection; 3=later declined switch; 1=damaged two devices and did not wish to continue biosimilar. Of the 10 gastroenterology switch back patients; 1=injection site pain; 2=lack of efficacy; 1=developed needle phobia; 1=latex allergy before injection; 1=switch detrimental to health; 2=unstable disease; 1=insomnia; 1=pregnancy. The 1 dermatology switch back patient reported injection site pain and bleeding.38/403 patients refused the switch and remained on the originator biologic (R;11, G;27, D;0). 29/403 patients had treatment cancellations and were switched to an alternative biologic (R;17, G;9, D;3). 32/403 patients stopped treatment (R;13, G;19, D;0). Treatment was withheld for 7/403 patients (R;4, G;2, D;1).Conclusion:The UHCW adalimumab biosimilar switch plan succeeded in switching a total of 66% of patients; thus an annual cost saving of £73,020. Injection site pain, most likely due to the biosimilar citrate content, and lack of efficacy according to patient perception and subsequent clinical review, were the most predominant causative themes for switch backs. Gastroenterology patients accounted for 71% (27/38) of the total switch refusals. Additional data regarding patient refusals, identifies future opportunities to improve patient counselling and drive further cost savings.

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&lt;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 &gt;10% switched back to RTX-O, the majority remained on treatment at short-term follow-up.

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).

P326 Reasons for and effectiveness of switching back to originator infliximab after a prior switch to CT-P13 biosimilar

Abstract Background In current clinical practice, patients with inflammatory bowel disease (IBD) treated with originator infliximab (IFX) have been or are being switched to biosimilar infliximab (CT-P13) because of lower costs and seemingly similar effectiveness of biosimilars. Over a one-year follow-up, 7%-26% of the patients discontinue CT-P13 treatment. Common reasons for CT-P13 discontinuation are (subjective) loss of response or adverse events. As a result of these newly experienced symptoms, patients are occasionally switched back to treatment with originator IFX. However, not much is currently known regarding reverse switching to originator IFX. We aimed to assess the prevalence of and the specific reasons for reverse switching to originator infliximab within 52-weeks after an initial conversion from originator infliximab to CT-P13 in patients with IBD. Additionally, we evaluated whether reinitiating originator infliximab led to the desired favourable effect and sustained infliximab use. Methods In this retrospective, multicentre cohort study, data of IBD patients from eight hospitals in the Netherlands were collected. Adult patients with IBD were eligible for inclusion if they were switched from infliximab originator to CT-P13 and had a follow-up time of at least 52 weeks after initial conversion. Reasons for re-switching were categorised into adverse events or loss of response on the biosimilar. Drug survival was analysed with a time-varying Cox proportional hazards model. Results A total of 684 patients with IBD were switched (516 Crohn’s disease, 168 ulcerative colitis). Reverse switching was seen in 74 (10.8%) patients after a median of 140 days (IQR 86–231). Reverse switchers were more often females (70.3% vs. 49.7%, p &amp;lt; 0.001) and had shorter originator treatment (4.0 [IQR 2.6–6.5] vs. 5.2 [IQR 3.0–7.5] years, p = 0.037) than those who stayed on CT-P13. A total of 105 symptoms for switching were reported. IBD-like symptoms (25.7%) and dermatological symptoms (21.9%) were the most common. Four patients had objectified loss of response. All regained response after switching back. IBD-like symptoms and dermatological symptoms were reversible in 74.1% and 87%, respectively. Overall reversibility of symptoms was 73.3%. Cox proportional hazards model with CT-P13/originator infliximab as time-varying covariate, yielded no difference in survival risk (hazard ratio 1.23, 95% CI 0.65–2.33). Conclusion Switching back to originator infliximab seems effective in patients with IBD, who experience adverse effects or loss of response after switching from originator to CT-P13. Switching patients back to originator infliximab might, therefore, be justified in case patients experience new side effects or loss of response after switching to CT-P13.

Reversible effect on lipids by switching from tenofovir disoproxil fumarate to tenofovir alafenamide and back.

The aim of the current study is to assess the effect of tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) on lipids in patients switching from TDF to TAF and back. Retrospective data collection on patients who were initially switched from TDF to TAF and switched back to TDF after generics of TDF became available. In total, 385 patients were included. Median duration of TDF exposure before switch was 317 weeks (interquartile range 172-494). After switching from TDF to TAF, mean total cholesterol (TC) increased from 186 ± 37 mg/dl at baseline to 206 ± 43 and 204 ± 43 mg/dl at weeks 12 and 24 (P < 0.001). The increase in TC was mainly due to an increase in LDL cholesterol. However, ratio of TC/HDL remained unchanged, indicating a simultaneous rise of LDL and HDL cholesterol. Baseline triglycerides increased from mean 153 ± 96 to 176 ± 120 and 176 ± 124 mg/dl at weeks, 12 and 24 (P < 0.001). From 385 patients 168 were switched back from TAF to TDF after median duration on TAF of 96 weeks (interquartile range 89-104). At switching back from TAF to TDF, mean TC was 202 ± 40 mg/dl and decreased at weeks 12 and 24 to 183 ± 41 and 185 ± 35 mg/dl (P < 0.001). Mean triglycerides were 163 ± 119 mg/dl and decreased to 145 ± 108 and 157 ± 112 mg/dl, respectively (P < 0.05). Patients with higher increases in TC after switching from TDF to TAF also showed more pronounced decreases after switching back. The results demonstrate a reversible effect on lipids by switching from TDF to TAF and back.

Medication changes after switching from CONCERTA® brand methylphenidate HCl to a generic long-acting formulation: A retrospective database study.

BackgroundObservational studies of switching from branded to generic formulations of the same drug substance often lack appropriate comparators for the subjects who switched. Three generic formulations were deemed equivalent to Concerta: an authorized generic (AG) identical except for external packaging, and two other generics (EG).ObjectiveCompare the incidence of a combined endpoint (switching back to Concerta, changing the use of immediate release methylphenidate (MPH), stopping all long-acting methylphenidate, or starting a new medication) among people switched from Concerta to the AG versus the EG.MethodsCohort study from the Truven CCAE database of people aged 6 to 65 diagnosed with ADHD, treated with Concerta, and switched to the EG or to the AG formulation.ResultsIn the EG arm 24.6% and in the AG arm 19.7% of subjects switched back to Concerta. The proportion of subjects meeting the combined endpoint was 39.5% in the EG arm, 32.9% in the AG arm, a crude risk ratio of 1.20 (95% CI 0.94, 1.54). After adjustment by propensity score stratification, the adjusted odds ratio (OR) was 1.23 (95% CI 0.90, 1.70). In an unplanned analysis using a different method of adjustment, the adjusted OR was 1.00 (95% CI 0.69, 1.44).DiscussionThis study did not detect a difference between the proportion of people who met the study endpoint in the two study arms, i.e. between those who switched to a generic formulation that was identical to Concerta except for external packaging and those who switched to the comparison generics. The high incidence of the combined endpoint in the AG arm demonstrates the need for an appropriate comparator in studies of this type.Trial registrationClinicalTrials.gov NCT02730572

Blood Lead Levels Among Children Aged

During April 25, 2014-October 15, 2015, approximately 99,000 residents of Flint, Michigan, wereaffected by changes in drinking water quality aftertheir water source was switched from the Detroit Water Authority (DWA), sourced from Lake Huron, tothe Flint Water System (FWS), sourced from the Flint River.* Because corrosion control was not used at the FWS water treatment plant, the levels of lead in Flint tap water increased over time. Adverse health effects are associated with lead exposure (1). On January 2, 2015, a water advisory was issued because of detection of high levels of trihalomethanes, byproducts of disinfectants.(†)(,)(§) Studies conducted by local and national investigators detected an increase in the prevalence of blood lead levels (BLLs) ≥5 µg/dL (the CDC reference level) among children aged <5 years living in Flint (2) and an increase in water lead levels after the water source switch (3). On October 16, 2015, the Flint water source was switched back to DWA, and residents were instructed to use filtered tap water for cooking and drinking. During that time, pregnant and breastfeeding women and children aged <6 years were advised to consume bottled water.(¶) To assess the impact on BLLs of consuming contaminated drinking water, CDC examined the distribution of BLLs ≥5 µg/dL among children aged <6 years before, during, and after the switch in water source. This analysis enabled determination of whether the odds of having BLLs ≥5 µg/dL before the switch differed from the odds during the switch to FWS (before and after the January 2, 2015, water advisory was issued), and after the switch back to DWA. Overall, among 9,422 blood lead tests in children aged <6 years, 284 (3.0%) BLLs were ≥5 µg/dL during April 25, 2013-March 16, 2016. The adjusted probability of having BLLs ≥5 µg/dL was 46% higher during the period after the switch from DWA to FWS (and before the January 2, 2015, water advisory) than during the period before the water switch to FWS. Although unrelated to lead in the water, the water advisory likely reduced tap water consumption and increased consumption of bottled water. Characterizing exposure to lead contaminated drinking water among children aged <6 years living in Flint can help guide appropriate interventions.

Effects of switching from ranibizumab to aflibercept in eyes with exudative age-related macular degeneration

AimsTo examine 12-month outcomes of eyes switching from intravitreal ranibizumab to aflibercept for neovascular age-related macular degeneration (nAMD).MethodsDatabase observational study of eyes with nAMD tracked by the Fight Retinal Blindness...

Feasibility and Efficacy of a Mass Switch from Latanoprost to Bimatoprost in Glaucoma Patients in a Prepaid Health Maintenance Organization

To assess the feasibility of an automatic switch of a large number of patients with glaucoma or suspicion of glaucoma from latanoprost to bimatoprost, and to compare the efficacy of the 2 prostaglandin analogs before and after the switch. Retrospective nonrandomized comparison. Forty-three thousand four hundred forty-one California patients and 538 patients at one Southern California clinical facility of a nationwide prepaid health maintenance organization (HMO) who were on either prostaglandin between March 2002 and December 2003 (21 months). Beginning in April 2002, patients on latanoprost were systemically switched to bimatoprost by the HMO pharmacy service after obtaining approval from the entire ophthalmology staff. PART 1: computerized dispensing records of California patients were retrieved. PART 2: medical records of patients at one clinical facility were reviewed. Rates of switching or switching back from one prostaglandin to another, intraocular pressure (IOP) control, and intolerability. PART 1: 17847 patients initially received latanoprost. Of them, 84.8% were switched from latanoprost to bimatoprost, and 13.0% were switched back to latanoprost. Twenty-five thousand five hundred ninety-four patients were started on bimatoprost without previous experience with latanoprost. Of them, 8.6% were later switched to latanoprost use instead. Patients who had previous experience with latanoprost had a statistically significantly higher rate of switching back to latanoprost after a period of bimatoprost use when compared with those who had no prior experience with latanoprost (13.0% vs. 8.6%, respectively; P<0.0001). PART 2: 309 patients were switched from latanoprost to bimatoprost. The mean IOP reduction of 0.51+/-2.77 mmHg (95% confidence interval, 0.20-0.82) after the switch was statistically significant (P = 0.001). Forty-one patients (13.3%) had a decrease of >3 mmHg of IOP. The statistical significance of the IOP reduction after the switch remains in the monotherapy group (P = 0.005) but not in the multitherapy group (P = 0.058). Thirty-three patients (10.7%) who were switched from latanoprost to bimatoprost discontinued bimatoprost and resumed latanoprost. A systematic pharmacy-level switch from latanoprost to bimatoprost in a nationwide HMO achieved a high switch rate, with little switching back. There was a small but statistically significant reduction in mean IOP after the switch. An appreciable proportion of patients switched had a clinically significant reduction of IOP.

Low Molecular Weight Heparin Reduces Triglyceride, VLDL and Cholesterol/HDL Levels in Hyperlipidemic Diabetic Patients on Hemodialysis

Background: Low molecular weight heparin (LMWH) provides a safe and effective alternative for hemodialysis anticoagulation. While unfractionated (UF) heparin has been implicated in hyperlipidemia, the effect of LMWH on the lipid profile in nondiabetic patients is controversial in chronic hemodialysis. The effect of LMWH in diabetic patients, a high risk group of hyperlipidemia, has not been studied. Method: LMWH was tested for its safety and efficacy in 10 nondiabetic Taiwanese patients. To evaluate influence of lipid profile, a crossover study was carried out in 10 type II diabetic patients with poor blood sugar control associated with high triglyceride (430.4 ± 101.1 mg/dl) and total cholesterol levels (219.2 ± 12.7 mg/dl) using UF heparin for more than 1 year. These patients were subjected to Fraxiparine, an LMWH, for 6 months and then switched back to UF heparin for another 6 months. Lipid profiles were measured every 2 months without prescribing lipid-lowering agents and the blood sugar was maintained at stationary levels. Results: LMWH is safe and effective in Taiwanese patients as a single bolus injection and maintains a 9.4% higher platelet count immediate postdialysis compared to UF heparin. With high HbA1c levels (9.6 ± 0.6%), mean triglyceride and VLDL levels started to decrease at the 4th month after LMWH treatment and reached a 34% reduction in triglyceride, a 26.2% reduction in VLDL, and a 19% reduction of total cholesterol/HDL ratio at the 6th month. Increments of triglyceride levels were found at the 6th month after a switch back to UF heparin. The levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein A-1 and B remained unchanged. Conclusion: LMWH may be beneficial to lipid control in hyperlipidemic diabetic patients on hemodialysis.