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Sequier L, Caron B, Danese S, Peyrin-Biroulet L. Clinical experience of using biosimilars in Crohn's disease and their effectiveness. Expert Opin Biol Ther 2024; 24:1145-1169. [PMID: 39269146 DOI: 10.1080/14712598.2024.2401616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 09/03/2024] [Indexed: 09/15/2024]
Abstract
INTRODUCTION The approval of biosimilars in the management of inflammatory bowel diseases (IBDs) has offered an answer to a growing concern about healthcare costs, and availability of treatments. Several studies have been conducted to demonstrate proof of biosimilars effectiveness as treatment in Crohn's disease (CD). AREAS COVERED Since 2013, the European Medicines Agency has approved five biosimilars for infliximab and eight for adalimumab. Initial data leading to approval were extrapolated from studies conducted in patients with rheumatological or dermatological diseases, but recent studies filled the gap of clinical data among patients with IBD. In this review, 75 studies were included, with data from a total of 20 707 patients with CD. Clinical data on biosimilars in the treatment of CD show equivalence in terms of efficacy, either as induction or maintenance of treatment and regardless of previous exposure to originator or other biosimilar. EXPERT OPINION Since biosimilar market entry, utilization of infliximab increased by 89.9% and by 22.4% for adalimumab in European countries. With a 10-year insight since the first approval of biosimilar in Europe, biosimilars prescriptions should be implemented in routine clinical practice given the efficacy and safety profile.
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Affiliation(s)
- Léa Sequier
- Department of Gastroenterology and Hepatology, Nîmes University Hospital, Carémeau Hospital, Nîmes, France
- Department of Gastroenterology and Hepatology A, Saint-Éloi Hospital, Montpellier, France
| | - Bénédicte Caron
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, Nancy, France
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
- Department of Immunology, Transplantation and Infectious Disease, Università Vita-Salute San Raffaele, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, Nancy, France
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France
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Patel S, Walsh J, Pinnell D, Pei S, Chen W, Rojas J, Rathod A, Johnson J, Gawron A, Curtis JR, Baker JF, Cannon GW, Wu D, Lai M, Sauer BC. Real-world experience with biosimilar infliximab-adba and infliximab-dyyb among infliximab-naïve patients with inflammatory bowel disease in the Veterans Health Administration. Medicine (Baltimore) 2024; 103:e39476. [PMID: 39287304 PMCID: PMC11404896 DOI: 10.1097/md.0000000000039476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 07/17/2024] [Accepted: 08/07/2024] [Indexed: 09/19/2024] Open
Abstract
The Veterans Health Administration (VHA) listed the infliximab (IFX) biosimilar, IFX-dyyb (Inflectra), on the Veterans Affairs National Formulary (VANF) in May 2017. In September 2018, biosimilar IFX-abda (Renflexis) became the VANF IFX product. The recommended formulary changes from one IFX biosimilar to another provided a unique opportunity to study IFX utilization patterns in IFX-naïve Veterans with Inflammatory Bowel Disease (IBD). This study aimed to describe IFX and healthcare utilization during the 365 days after initiation with IFX reference product (RP) or biosimilars IFX-dyyb and IFX-adba. This descriptive study was performed using the VHA Corporate Data Warehouse. All Veterans initiated on IFX-RP (Remicade) or biosimilars IFX-dyyb and IFX-adba between September 1, 2016 and December 30, 2019 were included and followed for 365 days. Veterans enrolled in the VHA for at least 365 days with no evidence of IFX before their index date were considered IFX-naïve. Continuous data on IFX use, laboratory measurements, and healthcare utilization were reported with means, 95% confidence interval (CI), medians, and interquartile ranges. Frequency, proportions, and 95% CIs were presented for categorical variables. Statistical tests included ANOVA and Kruskal-Wallis for continuous outcomes, Poisson regression for count-based outcomes (i.e., healthcare utilization visits), and Chi-square for dichotomous outcomes. The study identified 1763 IFX-naïve patients with IBD, and 785, 441, and 537 was indexed to RP, IFX-dyyb, and IFX-adba, respectively. Statistical differences were observed in IFX utilization measures related to dosing, adherence, and persistence. The proportion of days covered (PDC) during the 365-day follow-up period varied among the IFX groups: IFX-RP at 66%, IFX-dyyb at 60%, and IFX-abda at 69% (P value < .001). Persistence with the index IFX product during the 365-day follow-up period also varied: IFX-RP at 43%, IFX-dyyb at 32%, and IFX-abda at 51% (P value < .001). Healthcare utilization and laboratory findings were similar among the IFX groups. IFX utilization and laboratory patterns were clinically similar among the IFX biosimilars and RP groups, suggesting that providers did not modify their practice with biosimilars. Statistically significant differences in IFX utilization patterns are explained by formulary dynamics when the VANF product switched from IFX-dyyb to IFX-abda.
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Affiliation(s)
- Shardool Patel
- Salt Lake City Veterans Affairs Medical Center and Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Jessica Walsh
- Salt Lake City Veterans Affairs Medical Center and Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Derek Pinnell
- Salt Lake City Veterans Affairs Medical Center and Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Shaobo Pei
- Salt Lake City Veterans Affairs Medical Center and Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Wei Chen
- Salt Lake City Veterans Affairs Medical Center and Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Jorge Rojas
- Puget Sound Veterans Affairs Medical Center, Seattle, WA
- Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Anitha Rathod
- Salt Lake City Veterans Affairs Medical Center and Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Jessica Johnson
- Salt Lake City Veterans Affairs Medical Center and Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Andrew Gawron
- Salt Lake City Veterans Affairs Medical Center and Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Jeffrey R. Curtis
- Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL
| | - Joshua F. Baker
- Corporal Michael J. Crescenz VA Medical Center and School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Grant W. Cannon
- Salt Lake City Veterans Affairs Medical Center and Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - David Wu
- Merck and Company, Inc, Rahway, NJ
| | - Miao Lai
- Salt Lake City Veterans Affairs Medical Center and Department of Internal Medicine, University of Utah, Salt Lake City, UT
| | - Brian C. Sauer
- Salt Lake City Veterans Affairs Medical Center and Department of Internal Medicine, University of Utah, Salt Lake City, UT
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Lichtenstein GR, Soonasra A, Latymer M, Singh S, Feagan BG. Systematic review: effectiveness and safety of switching between originator infliximab and biosimilar infliximab in patients with inflammatory bowel disease. Expert Opin Biol Ther 2024; 24:691-708. [PMID: 38979696 DOI: 10.1080/14712598.2024.2378090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 07/05/2024] [Indexed: 07/10/2024]
Abstract
INTRODUCTION Infliximab (IFX) biosimilars are available to treat inflammatory bowel disease (IBD), offering cost reductions versus originator IFX in some jurisdictions. However, concerns remain regarding the efficacy and safety of originator-to-biosimilar switching. This systematic literature review evaluated safety and effectiveness of switching between IFX products in patients with IBD, including multiple switchers. METHODS Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials were searched to capture studies (2012-2022) including patients with IBD who switched between approved IFX products. Effectiveness outcomes: disease activity; disease severity; response to treatment; patient-reported outcomes (PROs). Safety outcomes: incidence and rate of adverse events (AEs); discontinuations due to AEs, failure rate; hospitalizations; surgeries. Immunogenicity outcomes (n, %): anti-drug antibodies; patients receiving concomitant immunomodulatory medication. RESULTS Data from 85 publications (81 observational, two randomized controlled trials) were included. Clinical effectiveness outcomes were consistent with the known profile of originator IFX with no difference after switching. There were no unexpected/serious AEs after switching, and rates of AEs were generally consistent with the known profile of IFX. CONCLUSIONS Most studies reported that clinical, PROs, and safety outcomes for originator-to-biosimilar switching were clinically equivalent to originator responses. Limited data are available regarding multiple switches. PROTOCOL REGISTRATION www.crd.york.ac.uk/prospero identifier is CRD42021289144.
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Affiliation(s)
- Gary R Lichtenstein
- Department of Internal Medicine, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA
| | - Arif Soonasra
- Global Medical Affairs, Pfizer Inc., Collegeville, PA, USA
| | - Mark Latymer
- Global Medical Affairs, Pfizer Ltd., Sandwich, UK
| | - Sheena Singh
- Value and Access, Curo, Envision Pharma Group, London, UK
| | - Brian G Feagan
- Robarts Research Institute, Western University, London, ON, Canada
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Meade S, Squirell E, Hoang TT, Chow J, Rosenfeld G. An Update on Anti-TNF Biosimilar Switching-Real-World Clinical Effectiveness and Safety. J Can Assoc Gastroenterol 2024; 7:30-45. [PMID: 38314175 PMCID: PMC10836972 DOI: 10.1093/jcag/gwad027] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2024] Open
Abstract
Background Biological medications for inflammatory bowel disease (IBD) account for a significant burden on provincial budgets. In an effort to curb these rising costs, nationwide switching to biosimilars is expected to be complete in Canada before the end of 2023. Biosimilar products do not require the same rigor for licensing as the originator and therefore there has been appropriate scepticism as to how biosimilars will perform in real-world practice. Methods We have performed a systematic review including real-world observational studies of adult patients with IBD. The primary outcome was clinical effectiveness and/or safety in patients who had switched from originator to biosimilar anti-TNF. Secondary outcomes included loss of response (LOR), treatment persistence or cessation and immunogenicity. Results We included 43 studies (7,462 patients [70 percent Crohn's disease: 30 percent ulcerative colitis]; 32 infliximab studies, and 11 adalimumab studies). For infliximab, 75 percent patients were in clinical remission at the time of switch and 75 percent maintained clinical remission beyond 12 months, compared to 78 percent of patients who continued originator. For adalimumab, 86 percent patients were in remission at the time of switch with 82 percent maintaining remission at 6 months follow-up. Injection site pain was higher in patients who switched to a citrate containing adalimumab biosimilar, compared with those who continued originator. All other outcomes (LOR, treatment cessation or persistence and serious adverse events) were similar to patients who continued originator (in comparator cohorts or the available literature). Conclusion Whilst ongoing vigilance is required, these data are reassuring to both patients and clinicians and will significantly help to reduce health-care costs across Canada.
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Affiliation(s)
- Susanna Meade
- University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | | | | | - James Chow
- BioPro Biologics Pharmacy, 845 West Broadway, Vancouver, BC V5Z1J9, Canada
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Fisher A, Kim JD, Dormuth CR. Monitoring a Mandatory Nonmedical Switching Policy from Originator to Biosimilar Infliximab in Patients with Inflammatory Bowel Diseases: A Population-Based Cohort Study. Gastroenterol Res Pract 2023; 2023:2794220. [PMID: 36911254 PMCID: PMC9995207 DOI: 10.1155/2023/2794220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 02/13/2023] [Accepted: 02/15/2023] [Indexed: 03/14/2023] Open
Abstract
Background On September 5, 2019, British Columbia announced a new policy (the Biosimilars Initiative) to switch from originator to biosimilar infliximab for patients with inflammatory bowel diseases. Objective To monitor the impacts of the policy on the use of medications and health services during the first year of the policy. Methods In this population-based cohort study, we used administrative health data to construct three historical cohorts and one policy cohort of patients with inflammatory bowel diseases who used the originator infliximab. We then monitored the cumulative incidence of medications and health services. Log-likelihood ratios were used to quantify differences between the policy cohort and the average of the historical cohorts. Results The cohorts included 1839-2368 users of the originator infliximab, ages 4-90 years, mean age 43 years. During the first year of follow-up, we found: (1) a 0.9% increase in the first dispensation of infliximab, biosimilar, or originator; (2) a 16.2% increase in infliximab dose escalation; (3) a decrease of 2.4% in the dispensation of antibiotics and a 2.6% decrease in new use of prednison; (4) an anticipated increase in visits to physicians and gastroenterologists to manage switching to biosimilars (24.0%); (5) a 4.0% decrease in discharges from hospital; and (6) a 2.9% decrease in emergency admissions to hospital. Conclusion British Columbia's Biosimilars Initiative for nonmedical switching from originator to biosimilar infliximab for inflammatory bowel diseases was not associated with harmful impacts on medications and health services use. An increase in dose escalation was accompanied by an improvement in health status proxies.
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Affiliation(s)
- Anat Fisher
- Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
| | - Jason D. Kim
- Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
| | - Colin R. Dormuth
- Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia Victoria Office, Suite 210, 1110 Government Street, Victoria, BC V8W 1Y2, Canada
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Abraham B, Eksteen B, Nedd K, Kale H, Patel D, Stephens J, Shelbaya A, Chambers R, Soonasra A. Impact of Infliximab-dyyb (Infliximab Biosimilar) on Clinical and Patient-Reported Outcomes: 1-Year Follow-up Results from an Observational Real-World Study Among Patients with Inflammatory Bowel Disease in the US and Canada (the ONWARD Study). Adv Ther 2022; 39:2109-2127. [PMID: 35296993 PMCID: PMC9056488 DOI: 10.1007/s12325-022-02104-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 02/22/2022] [Indexed: 11/26/2022]
Abstract
Introduction To date, there are limited real-world studies published on the use of infliximab-dyyb, a biosimilar to reference product (RP) infliximab approved for the treatment of moderate to severe inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC) in North America. This study examined utilization patterns and the effects of infliximab-dyyb on clinical outcomes, patient-reported outcomes (PROs), and healthcare resource use (HCRU) in IBD patients in a real-world setting. Methods In this prospective, observational study, adult IBD patients in the US and Canada were recruited to initiate treatment with infliximab-dyyb and followed for 12 months. Patients included biologic-naïve users of infliximab-dyyb and patients switching from RP infliximab or other biologics to infliximab-dyyb. Partial Mayo (pMAYO) and Harvey Bradshaw Index (HBI) scores measured clinical outcomes for the UC and CD cohorts, respectively. Key PRO measures included the SIBDQ, EQ-VAS, and psychological outcomes. In addition, work productivity, HCRU, and adverse events (AEs) were assessed. Results A total of 67 CD and 48 UC patients were enrolled (51% female; mean age 44 years; 87% Caucasian; mean BMI 27.9). Thirty-nine patients were biologic-naïve, 57 switched from RP infliximab, and 19 switched from other biologics. Among UC biologic-naïve users, pMAYO decreased from 5.67 to 1.09 (p < 0.0001) and the remission rate increased from 5.6 to 90.9% (p = 0.0015). For UC patients switching from RP infliximab, pMAYO decreased from 1.38 to 0.29 (p = 0.0103). For CD biologic-naïve users, HBI scores and remission rates did not significantly change. The scores on all the PROs significantly improved from baseline to 12 months. A total of 22 AEs occurred consistent with the known AE profile for infliximab. Conclusions Clinical outcomes among biologic-naïve users of infliximab-dyyb improved for UC and were maintained for CD patients. Biologic-naïve users of infliximab-dyyb showed significant improvements in PROs. Patients switching from RP infliximab to infliximab-dyyb maintained their clinical outcomes and PROs. Trial Registration ClinicalTrials.gov Registration Number: NCT03801928 (February 23, 2018). Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02104-6.
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Affiliation(s)
| | | | - Khan Nedd
- Infusion Associates, Grand Rapids, MI USA
| | - Hrishikesh Kale
- OPEN Health, 4350 East-West Hwy #1100, Bethesda, MD 20814 USA
| | - Dipen Patel
- OPEN Health, 4350 East-West Hwy #1100, Bethesda, MD 20814 USA
| | | | - Ahmed Shelbaya
- Mailman School of Public Health, Columbia University, New York, NY USA
- Pfizer, New York, NY USA
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Lin I, Melsheimer R, Bhak RH, Lefebvre P, DerSarkissian M, Emond B, Lax A, Nguyen C, Wu M, Young-Xu Y. Impact of switching to infliximab biosimilars on treatment patterns among US veterans receiving innovator infliximab. Curr Med Res Opin 2022; 38:613-627. [PMID: 35125053 DOI: 10.1080/03007995.2022.2037846] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVE To compare treatment patterns of United States (US) veterans stable on innovator infliximab (IFX) who switched to an IFX biosimilar (switchers) or remained on innovator IFX (continuers). METHODS US Veterans Healthcare Administration data (01/2012-12/2019) were used to identify adults with rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis (PsO), ankylosing spondylitis (AS), or Crohn's disease and ulcerative colitis (i.e. inflammatory bowel disease [IBD]), treated with innovator or biosimilar IFX. Index date was the first IFX biosimilar administration for switchers or a random innovator IFX administration for continuers. Patients were required to have ≥5 innovator IFX administrations during the 12 months pre-index (prevalent population). Patients with ≥12 months of observation prior to the first innovator IFX administration were analyzed as the primary population (incident population), and data were assessed from start of innovator IFX. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Treatment patterns were evaluated post-index; continuers were censored before switching to IFX biosimilar. Discontinuation was defined as switching to another biologic (including innovator IFX) or having ≥120 days between 2 consecutive index treatment records. RESULTS In the incident population, mean [median] duration of follow-up was 737 [796] days among switchers (N = 838) and 479 [337] days among continuers (N = 849). Compared to continuers, switchers were 2.88-times more likely to discontinue index therapy (hazard ratio [HR] = 2.88, p < .001) and 4.99-times more likely to switch to another innovator biologic (HR = 4.99, p < .001). Of 653 switchers switching to another innovator biologic, 594 (91.0%) switched back to innovator IFX. Results were similar among the prevalent population and RA and IBD subgroups. CONCLUSION Patients switching from innovator to biosimilar IFX were more likely to discontinue treatment and switch to another innovator biologic (notably back to innovator IFX) than those remaining on innovator IFX; however, reasons for discontinuation and switching are unknown.
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Affiliation(s)
- Iris Lin
- Janssen Scientific Affairs, LLC, Horsham, PA, USA
| | | | | | | | | | - Bruno Emond
- Analysis Group, Inc, Montréal, Québec, Canada
| | - Angela Lax
- Analysis Group, Inc, Boston, Massachusetts, USA
| | | | - Melody Wu
- Analysis Group, Inc, Boston, Massachusetts, USA
| | - Yinong Young-Xu
- White River Junction VA Medical Center, White River Junction, VT, USA
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Abidin AZ, Snoswell CL, Shafiee Hanjani L, Callaghan G, Edmonds M. Infliximab switching from reference product to biosimilar: a review of evidence regarding the clinical efficacy, safety profile and immunogenicity. JOURNAL OF PHARMACY PRACTICE AND RESEARCH 2021. [DOI: 10.1002/jppr.1754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Ahmad Zainal Abidin
- Centre for Health Services Research The University of Queensland Brisbane Qld Australia
| | - Centaine L. Snoswell
- Centre for Health Services Research The University of Queensland Brisbane Qld Australia
- Pharmacy Department Princess Alexandra Hospital Brisbane Qld Australia
- School of Pharmacy The University of Queensland Brisbane Qld Australia
| | - Leila Shafiee Hanjani
- Centre for Health Services Research The University of Queensland Brisbane Qld Australia
| | - Gavin Callaghan
- Pharmacy Department Princess Alexandra Hospital Brisbane Qld Australia
| | - Michelle Edmonds
- Pharmacy Department Princess Alexandra Hospital Brisbane Qld Australia
- Pharmacy Department Royal Darwin Hospital Darwin NT Australia
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Smith JT, Velayos FS, Niu F, Liu V, Delate T, Pola S, Le K, Hui RL. Retrospective Cohort Study Comparing Infliximab-dyyb and Infliximab in Biologic-Naive Patients With Inflammatory Bowel Disease in the United States. CROHN'S & COLITIS 360 2021; 3:otab051. [PMID: 36776661 PMCID: PMC9802363 DOI: 10.1093/crocol/otab051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Indexed: 11/13/2022] Open
Abstract
Background Real-world assessments of biosimilars are needed to understand their effectiveness and safety in practice settings that may differ from those seen in clinical trials or healthcare systems in different countries. To assess the effectiveness and safety of a biosimilar (infliximab-dyyb) and its reference product (infliximab) in patients with inflammatory bowel disease (IBD) in the United States. Methods We conducted a retrospective cohort study of biologic-naive patients with IBD who started treatment with infliximab-dyyb or infliximab. The study included 3206 patients identified through electronic health records in a US integrated healthcare delivery system. The effectiveness outcome was a composite of IBD-related surgery, IBD-related emergency room visit, and IBD-related hospitalization within 12 months of initiation. Safety outcomes included incidence of any or serious infection, cancer, acute liver dysfunction, and tuberculosis. We used a non-inferiority test with an upper-limit margin of 10% to analyze effectiveness. Doubly robust methods incorporating Cox proportional hazard regression with standardized inverse probability of treatment weighting were used to analyze both effectiveness and safety outcomes. Results The composite effectiveness outcome occurred in 107 of 870 patients (12.3%) in the infliximab-dyyb and 379 of 2336 patients (16.2%) in the infliximab groups. Infliximab-dyyb was non-inferior (P < .01) and was not different (hazard ratio [HR] 0.81; confidence interval [CI] 0.65-1.01; P = .06) to infliximab. Safety outcomes were not different between infliximab-dyyb and infliximab for any infections (HR 1.01; CI 0.86-1.17; P = .95), serious infections (HR 0.83; CI 0.54-1.26; P = .38), cancers (HR 0.83; CI 0.44-1.54; P = .55), and tuberculosis (HR 0.59; CI 0.10-3.55; P = .57). Conclusions Initiation of infliximab-dyyb was non-inferior to infliximab among biologic-naive patients with IBD in an US integrated healthcare delivery system.
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Affiliation(s)
- Joshua T Smith
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
| | - Fernando S Velayos
- Division of Gastroenterology and Hepatology, The Permanente Medical Group, San Francisco, California, USA
| | - Fang Niu
- Kaiser Permanente National Pharmacy, Pharmacy Outcomes Research Group, National Pharmacy Services, Downey, California, USA
| | - Vincent Liu
- Division of Research, Kaiser Permanente National Pharmacy, Oakland, California, USA
| | - Thomas Delate
- Pharmacy Outcomes Research Group, National Pharmacy Services, Aurora, Colorado, USA
| | - Suresh Pola
- Kaiser Permanente National Pharmacy, Department of Gastroenterology, Southern California Permanente Medical Group, San Diego, California, USA
| | - Kim Le
- Kaiser Permanente National Pharmacy, Drug Evaluation, Strategy and Outcomes, National Pharmacy Services, Kaiser Permanente National Pharmacy, Downey, California, USA
| | - Rita L Hui
- Kaiser Permanente National Pharmacy, Pharmacy Outcomes Research Group, National Pharmacy Services, Oakland, California, USA,Address correspondence to: Rita L. Hui, PharmD, MS, Pharmacy Outcomes Research Group, National Pharmacy Services, Kaiser Permanente, 1800 Harrison St., #1301, Oakland, CA 94612, USA ()
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Afzali A, Furtner D, Melsheimer R, Molloy PJ. The Automatic Substitution of Biosimilars: Definitions of Interchangeability are not Interchangeable. Adv Ther 2021; 38:2077-2093. [PMID: 33745111 PMCID: PMC8107170 DOI: 10.1007/s12325-021-01688-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 02/26/2021] [Indexed: 02/07/2023]
Abstract
In the USA, an interchangeability designation provides biosimilar sponsors with a pathway for achieving what is standard for small-molecule generics: pharmacy-level auto-substitution for an innovator. No other major health authority links interchangeability to automatic substitution, as all require the involvement of the prescriber or patient in a medication change. This editorial considers the clinical impact and practicality of auto-substitution. First, interchangeability is linked to non-medical switching (NMS), the practice of switching treatment in patients with stable disease for non-clinical reasons. NMS may generate negative sentiment in those unwilling or reluctant to switch, which can adversely impact treatment outcomes (i.e., nocebo effect). Indeed, in real-world studies of tumor necrosis factor inhibitors, discontinuation rates have been shown to be higher in patients switched to biosimilars for non-medical reasons than in historical cohorts maintained on innovators. Second, interchangeability may impede pharmacovigilance and traceability, as not all jurisdictions require innovators and biosimilars to have distinct biologic names. Third, an interchangeability designation from the US Food and Drug Administration only permits a biosimilar to be automatically substituted for its innovator, not other biosimilars (if available). Pharmacist education would be needed to avoid off-label, automatic substitution among biosimilars of a single innovator. Last, once granted, an interchangeability designation exists in perpetuity under current US federal law. However, the supply chains of innovators and biosimilars are maintained independently, with no requirement for reconfirmation of biosimilarity or interchangeability. We feel that additional guidance is needed for the auto-substitution of biosimilars and innovators to become a reality.
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Fitzgerald T, Melsheimer R, Lafeuille MH, Lefebvre P, Morrison L, Woodruff K, Lin I, Emond B. Switching and Discontinuation Patterns Among Patients Stable on Originator Infliximab Who Switched to an Infliximab Biosimilar or Remained on Originator Infliximab. Biologics 2021; 15:1-15. [PMID: 33442230 PMCID: PMC7797299 DOI: 10.2147/btt.s285610] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 12/16/2020] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To compare switching and discontinuation patterns of patients stable on originator infliximab (IFX) who switched to an IFX biosimilar (switchers) or remained on originator IFX (continuers) in the United States. METHODS Symphony Health Solutions' Patient Transactional Datasets (10/2012-03/2019) were used to identify adults with ≥2 claims for either rheumatoid arthritis (RA), psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, or inflammatory bowel disease (IBD); and ≥1 claim for originator or biosimilar IFX. The index date was the first IFX biosimilar claim for switchers or a random originator IFX claim for continuers. All patients were required to have ≥5 originator IFX claims during the 12 months pre-index (prevalent population). The subset of patients with ≥12 months of observation prior to the first originator IFX claim was also analyzed (incident population). Switchers were matched 1:3 to continuers. Discontinuation was defined as having ≥120 days between 2 consecutive index treatment claims. RESULTS Prevalent switchers (N=1109) were 3.57-times more likely than continuers (N=3327) to switch to another originator biologic (hazard ratio [HR]=3.57, p<0.001). Of 249 prevalent switchers who switched to another originator biologic, 200 (80.3%) switched back to originator IFX. Incident switchers (N=571) were 2.55-times more likely than continuers (N=1713) to switch to another originator biologic (HR=2.55, p<0.001). Of 118 incident switchers who switched to another originator biologic, 90 (76.3%) switched back to originator IFX. Prevalent switchers were 1.25-times more likely than continuers to discontinue index therapy (HR=1.25, p<0.001). Similar results were observed in RA (prevalent population; switching: HR=3.49, p<0.001; discontinuation: HR=1.23, p=0.009) and IBD (prevalent population; switching: HR=3.82, p<0.001; discontinuation: HR=1.29, p=0.003) subgroups. CONCLUSION Patients switching from originator to biosimilar IFX were more likely to switch to another originator biologic (notably back to originator IFX) and discontinue index treatment than those remaining on originator IFX; however, reasons for switching are unknown.
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Affiliation(s)
- Timothy Fitzgerald
- Real World Value & Evidence, Janssen Scientific Affairs, LLC, Titusville, New Jersey, USA
| | | | | | | | | | - Kimberly Woodruff
- Real World Value & Evidence, Janssen Scientific Affairs, LLC, Titusville, New Jersey, USA
| | - Iris Lin
- Real World Value & Evidence, Janssen Scientific Affairs, LLC, Titusville, New Jersey, USA
| | - Bruno Emond
- Analysis Group, Inc., Montréal, Québec, Canada
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Talathi S, Baig KRKK. Biosimilars in inflammatory bowel disease. J Dig Dis 2020; 21:610-620. [PMID: 32920972 DOI: 10.1111/1751-2980.12940] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/11/2020] [Accepted: 09/09/2020] [Indexed: 12/11/2022]
Abstract
The advent of biologics has changed outcomes in many chronic conditions, including inflammatory bowel disease (IBD). Biologics have been used for the induction and remission of ulcerative colitis and Crohn's disease for almost two decades and are effective in patients who used to fail conventional treatment with steroids, immunomodulators. The use of biologics in the treatment of IBD has increased over the last few years, partly due to the rise in its incidence and the use of biologics as a first-line treatment in severe disease as well as in complicated diseases like penetrating/fistulating Crohn's disease. However, their use is associated with a significant burden to the society with respect to healthcare costs, resulting in the premature discontinuation of therapy in some patients, leading to exacerbations and complications. The introduction of biosimilars a decade ago seems to be a promising approach to reducing the costs related to therapy. Since their introduction, numerous studies conducted in adults and some in children show the efficacy of biosimilars with a similar side-effect profile to biologics. This review discusses the history of biosimilars in the treatment of IBD, enumerates several such studies and discusses the possibility of using biosimilars in the future.
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Affiliation(s)
- Saurabh Talathi
- Department of Pediatrics, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
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Pugliese D, Guidi L, Privitera G, Bertani L, Tolusso B, Papparella LG, Maltinti S, Di Mario C, Onali S, Ceccarelli L, Rapaccini GL, Scaldaferri F, Gremese E, Gasbarrini A, Costa F, Armuzzi A. Switching from IFX originator to biosimilar CT-P13 does not impact effectiveness,safety and immunogenicity in a large cohort of IBD patients. Expert Opin Biol Ther 2020; 21:97-104. [PMID: 33074723 DOI: 10.1080/14712598.2020.1839045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Switching from IFX originator to CT-P13 is safe; however, little data on immunogenicity exists. RESEARCH DESIGN AND METHODS Consecutive IBD patients on IFX originator were switched to CT-P13 and followed-up for 12 months. Clinical activity, infliximab trough levels (ITLs), anti-drug antibodies (ATIs), and adverse events were recorded at predefined timepoints (baseline, second CT-P13 infusion, 6 and 12 months). The outcomes investigated were immunogenicity, pharmacokinetics, effectiveness and safety. RESULTS 119 patients were switched to CT-P13 after a median time with IFX of 5.8 years. No changes in mean ITLs were observed. ATIs were detected in 30 patients (25.2%): 14 before and 16 after switch. Mean persistent ATIs were significantly higher compared to mean transient ones (109.74 ng/mL ±84.70 vs 18.22 ng/mL ±11.37, p < 0.001), with significantly lower ITLs associated (mean 0.32 µg/mL ±0.6 vs 3.08 µg/mL ±3.22, p < 0.001). A significant decrease of patients in steroid-fee clinical remission was observed after the switch (p = 0.004), with subsequent improvement at 6 months (p = 0.005). Eighteen patients (15.1%) discontinued IFX, only 6 (5%) for loss of response. CONCLUSIONS Switching from infliximab originator to CT-P13 seems safe and effective, without differences in immunogenicity. A temporary reduction of clinical benefit after switching could be potentially explained by a 'nocebo-effect response'.
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Affiliation(s)
- Daniela Pugliese
- CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS , Rome, Italy
| | - Luisa Guidi
- CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS , Rome, Italy.,Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore , Rome, Italy
| | - Giuseppe Privitera
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore , Rome, Italy
| | - Lorenzo Bertani
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa , Pisa, Italy
| | - Barbara Tolusso
- OU Rheumatology Columbus, Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome, Italy
| | - Luigi Giovanni Papparella
- CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS , Rome, Italy
| | - Simona Maltinti
- Department of New Technologies and Translational Research in Medicine and Surgery, University of Pisa , Pisa, Italy
| | - Clara Di Mario
- OU Rheumatology Columbus, Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome, Italy
| | - Sara Onali
- CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS , Rome, Italy
| | - Linda Ceccarelli
- Division of Rheumatology, Università Cattolica del Sacro Cuore , Rome, Italy
| | - Gian Lodovico Rapaccini
- CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS , Rome, Italy.,Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore , Rome, Italy
| | - Franco Scaldaferri
- CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS , Rome, Italy
| | - Elisa Gremese
- OU Rheumatology Columbus, Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome, Italy
| | - Antonio Gasbarrini
- CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS , Rome, Italy.,Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore , Rome, Italy
| | - Francesco Costa
- Department of General Surgery and Gastroenterology, IBD Unit, Pisa University Hospital , Pisa, Italy
| | - Alessandro Armuzzi
- CEMAD - IBD UNIT - Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS , Rome, Italy.,Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore , Rome, Italy
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