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The Lancet. Rheumatology Jul 2024For cost-saving purposes, children and young people with juvenile idiopathic arthritis (JIA) are being switched (for non-medical reasons) from biological originators to...
Outcomes after anti-tumour necrosis factor originator to biosimilar switching in children and young people with juvenile idiopathic arthritis in the UK: a national cohort study.
BACKGROUND
For cost-saving purposes, children and young people with juvenile idiopathic arthritis (JIA) are being switched (for non-medical reasons) from biological originators to biosimilars. Here, we aimed to investigate those who switched from an anti-tumour necrosis factor (TNF) originator to a biosimilar, regarding drug survival and disease activity, compared with a matched cohort who continued the originator.
METHODS
This analysis included all patients in the UK JIA Biologics Register switching directly from an anti-TNF originator to a biosimilar of the same product. All patients were matched (age, sex, disease duration, calendar year of when patients started originator therapy, line of therapy, and International League of Associations for Rheumatology [ILAR] category) to patients continuing the originator. For those matched successfully, a Cox proportional hazard model assessed whether drug persistence differed between those who switched compared with those who continued the originator. Overall change in the 71-joint juvenile arthritis disease activity score and the proportion of patients with a clinically important worsening score (by ≥1·7 units) after 6 months was compared between cohorts. This analysis was designed to address a priority research area set by our patient partners.
FINDINGS
There were 224 children and young people with non-systemic JIA (139 [62%] were female, and 85 [38%] were male) identified as switching from a biological originator to a biosimilar of the same product from Jan 1, 2017, to July 7, 2023. 143 (64%) patients were originally on adalimumab, 56 (25%) on etanercept, and 25 (11%) on infliximab. Of these, 164 patients were matched successfully to those continuing the originator. There was no evidence that patients switching were more likely to stop treatment compared with those continuing the originator, with a hazard ratio of 1·46 (95% CI 0·93-2·30). Of the 51 patients in the biosimilar group who stopped treatment, 18 (35%) switched back to the originator (14 in the first year), 28 (55%) started a different biological drug, and five (10%) discontinued all treatment by the last follow-up. Of the 87 matched patients with available disease activity, there was no evidence that JADAS-71 worsened more after 6 months, with an odds ratio of 0·71 (95% CI 0·34-1·51; p=0·38).
INTERPRETATION
In this matched comparative effectiveness analysis, children and young people with JIA switched from originators to biosimilars. Disease activity was similar between patients switching compared with those continuing the originator. Three quarters of patients were still receiving their biosimilar after 1 year, with switching back to originator uncommon, at only 9% after 1 year, suggesting good tolerability of non-medical switching in this patient population. This information is reassuring to clinicians and patients regarding the effect of non-medical biological switching.
FUNDING
British Society for Rheumatology, Versus Arthritis, and National Institutes for Health Research Manchester Biomedical Research Centre.
Topics: Humans; Arthritis, Juvenile; Male; Female; Biosimilar Pharmaceuticals; Child; Adolescent; Drug Substitution; Antirheumatic Agents; United Kingdom; Cohort Studies; Treatment Outcome; Child, Preschool; Tumor Necrosis Factor-alpha; Infliximab; Adalimumab; Etanercept; Biological Products
PubMed: 38843858
DOI: 10.1016/S2665-9913(24)00087-0 -
PloS One 2024To evaluate the impact of the entry of biosimilars on the pricing of eight biologic products in 57 countries and regions.
OBJECTIVE
To evaluate the impact of the entry of biosimilars on the pricing of eight biologic products in 57 countries and regions.
METHODS
We utilized an interrupted time series design and IQVIA MIDAS® data to analyze the annual sales data of eight biologic products (adalimumab, bevacizumab, epoetin, etanercept, filgrastim, infliximab, pegfilgrastim, and trastuzumab) across 57 countries and regions from January 1, 2012, to December 31, 2019. We examined the immediate and long-term changes in biologics ex-manufacturer pricing following the entry of biosimilars to the market.
RESULTS
Following the entry of biosimilars, the average price per dose of biologic product was immediately reduced by $438 for trastuzumab, $112 for infliximab, and $110 for bevacizumab. The persistent effect of biosimilars' market entry led to further reductions in price per dose every year: by $49 for adalimumab, $290 for filgrastim, $21 for infliximab, and $189 for trastuzumab. Similarly, we analyzed the impact of biosimilars on four biologics' prices in the US, where the prices of three biologics significantly decreased every year, with filgrastim, pegfilgrastim, and infliximab decreasing by $955, $753, and $104, respectively.
CONCLUSIONS
The introduction of biosimilars has significantly reduced the prices of biologics both globally and in the US. These findings not only demonstrate the economic benefits of increasing biosimilar utilization, but also emphasize the importance of biosimilars in controlling healthcare costs. Policies should aim to expand the availability of biosimilars to counteract the exponential growth of medical spending caused by the use of biologics.
Topics: Biosimilar Pharmaceuticals; Humans; Infliximab; Filgrastim; Biological Products; Drug Costs; Adalimumab; Etanercept; Trastuzumab; Costs and Cost Analysis; Polyethylene Glycols
PubMed: 38843282
DOI: 10.1371/journal.pone.0304851 -
Indian Journal of Dermatology 2024In recent years, with the increased usage of tumour necrosis factor (TNF) inhibitors, more side effects have been revealed. Paradoxical psoriasis, including psoriasis...
In recent years, with the increased usage of tumour necrosis factor (TNF) inhibitors, more side effects have been revealed. Paradoxical psoriasis, including psoriasis vulgaris, palmoplantar pustulosis, scalp psoriasis and their combinations, is a common adverse effect. However, erythrodermic psoriasis associated with alopecia due to anti-TNF-α is rarely reported in the literature. We report a 44-year-old woman who developed erythrodermic psoriasis associated with diffuse alopecia during her treatment with adalimumab for palmoplantar pustulosis.
PubMed: 38841217
DOI: 10.4103/ijd.ijd_155_23 -
Cureus Jun 2024Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One... (Review)
Review
Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One of the most successful lines for inducing and maintaining clinical remission in subjects with UC is biological therapy with anti-tumor necrosis factor α (anti-TNF) agents, including adalimumab (ADA) and infliximab (IFX). This meta-analysis is an attempt to obtain complementary information driven by real-world experience (RWE) concerning the efficacy and safety of two of the most popular anti-TNFs in treating UC. This is a systematic review and meta-analysis of RWE studies comparing ADA and IFX as naïve anti-TNF agents for the treatment of subjects with UC. Studies were obtained by searching Scopus, Google Scholar, the Cochrane Central Register of Controlled Trials, Embase, and the PubMed Central databases. Patients treated with IFX showed significantly higher induction responses. No statistically significant difference was found in the comparison of response in the maintenance treatment period. Higher overall adverse events were related to IFX treatment, with serious adverse events that were nonsignificantly higher in the ADA-treated group. In conclusion, IFX demonstrated significantly higher induction responses compared to ADA in patients with moderate-to-severe UC. IFX was associated with higher overall adverse events, whereas serious adverse events were non-significantly higher in the ADA-treated group. IFX may be favored as a first-line agent for its induction efficacy, and the choice between IFX and ADA should be individualized based on comprehensive clinical evaluation.
PubMed: 38835557
DOI: 10.7759/cureus.61547 -
Clinical, Cosmetic and Investigational... 2024This case study outlines the management of a 24-year-old male with a history of juvenile nephronophthisis who underwent renal transplantation at age 12 and later...
This case study outlines the management of a 24-year-old male with a history of juvenile nephronophthisis who underwent renal transplantation at age 12 and later required dialysis at 18 due to chronic rejection and hypertension. Subsequently, the patient developed severe Hidradenitis Suppurativa (HS) affecting the axillary, groin, and gluteal regions. Despite undergoing various systemic and intravenous antibiotic therapies, as well as Adalimumab treatment, the HS remained refractory. Adalimumab was discontinued due to a detected ejection fraction of 45% during cardiologic follow-up, likely due to COVID-19 related myocarditis. Following this, the patient was initiated on secukinumab therapy, initially undergoing an induction phase followed by maintenance dosing. Significant improvements were observed in quality of life, pain scores, and HS activity after 5 weeks of secukinumab therapy, with sustained benefits at the 6-month follow-up. Secukinumab was well tolerated, with no reported adverse events. This case underscores the effectiveness and safety of secukinumab as a therapeutic option for refractory HS, particularly in patients with comorbidities such as renal transplant recipients.
PubMed: 38831783
DOI: 10.2147/CCID.S468268 -
Therapeutic Advances in Gastroenterology 2024Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's...
Development and validation of a novel therapeutic drug monitoring-based nomogram for prediction of primary endoscopic response to anti-TNF therapy in active Crohn's disease.
BACKGROUND
Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial.
OBJECTIVES
To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram.
DESIGN
Cross-sectional study.
METHODS
The simplified endoscopic activity score for CD (SES-CD), Crohn's disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed.
RESULTS
The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort ( < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD ( < 0.001), CDAI ( < 0.001), and C-reactive protein (CRP) ( < 0.001) at week 14 post-IFX therapy in the development cohort. Furthermore, the receiver operating characteristic curve revealed that an optimal level of IFX (4.80 μg/mL) and ADA (8.80 μg/mL) exhibited the best performance in predicting endoscopic response. Concomitantly, we developed a novel nomogram prediction model based on the results of multivariate logistic regression analysis, which consisted of CRP, albumin (Alb), and anti-TNF trough levels at week 14. The nomogram showed significant discrimination and calibration for both IFX and ADA in the development cohort and performed well in the external validation cohort.
CONCLUSION
This study demonstrates a robust association between serum concentrations of IFX, ADA, Alb, and CRP and primary endoscopic response in active CD patients. Importantly, the TDM- and laboratory marker-based nomogram may be used to evaluate the primary endoscopic response to anti-TNF therapy, especially for optimizing treatment strategies and switching therapy in CD patients.
PubMed: 38827646
DOI: 10.1177/17562848241256237 -
Therapeutic Advances in Chronic Disease 2024Hidradenitis suppurativa (HS) is an inflammatory skin condition with an underlying inflammatory process. Due to the limited efficacy of available treatments, HS remains... (Review)
Review
Hidradenitis suppurativa (HS) is an inflammatory skin condition with an underlying inflammatory process. Due to the limited efficacy of available treatments, HS remains a therapeutic challenge. The safety and efficacy of tumor necrosis factor-α (TNF-α) inhibitors, adalimumab, infliximab, and etanercept, are well studied in this patient population, and in some cases, HS was unresponsive to them. In recent years, evidence has been growing regarding the application of other anti-TNFs, including certolizumab pegol (CPZ) and golimumab. We sought to evaluate the overall safety and efficacy of golimumab and CPZ in the management of HS. A comprehensive search was performed on the PubMed, Scopus, Web of Science, and Ovid Embase databases, as well as the Google Scholar search engine from initiation to 31 August 2023. A total of nine and four studies used CPZ and golimumab to treat HS, respectively. Individuals with concomitant inflammatory immune-mediated diseases, pregnant females, and patients who were refractory to previous treatments achieved a Hidradenitis Suppurativa Clinical Response following CPZ administration. Also, golimumab showed promise in treating recalcitrant HS after the failure of other treatments, such as adalimumab and anti-interleukin-1. CPZ and golimumab can be efficacious treatment options for moderate-to-severe HS, especially in patients who are unresponsive to other TNF inhibitors, such as adalimumab.
PubMed: 38827348
DOI: 10.1177/20406223241257342 -
Therapeutic Advances in Musculoskeletal... 2024The aim of the Severe Psoriatic arthritis - Early intervEntion to control Disease trial is to compare outcomes in psoriatic arthritis (PsA) patients with poor prognostic...
The protocol of a clinical effectiveness trial comparing standard step-up care, early combination DMARD therapy and early use of TNF inhibitors for the treatment of moderate to severe psoriatic arthritis: the 3-arm parallel group SPEED randomized controlled trial.
OBJECTIVES
The aim of the Severe Psoriatic arthritis - Early intervEntion to control Disease trial is to compare outcomes in psoriatic arthritis (PsA) patients with poor prognostic factors treated with standard step-up conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), combination csDMARDs or a course of early biologics.
DESIGN
This multicentre UK trial was embedded within the MONITOR-PsA cohort, which uses a trial within cohort design.
METHODS AND ANALYSIS
Patients with newly diagnosed PsA and at least one poor prognostic factor (polyarthritis, C-reactive protein >5 mg/dL, health assessment questionnaire >1, radiographic erosions) were randomized equally and open-label to either standard care with 'step-up' csDMARD therapy, initial therapy with combination csDMARDs (methotrexate with either sulfasalazine or leflunomide) or to early biologics induction therapy (adalimumab plus methotrexate). The primary outcome is the PsA disease activity score at week 24.
ETHICS
Ethical approval for the study was granted by the South Central Research Ethics Committee (ref 18/SC/0107).
DISCUSSION
Treatment recommendations for PsA suggest more intensive therapy for those with poor prognostic factors but there are no studies that have previously used prognostic factors to guide therapy. Applying initial intensive therapy has shown improved outcomes in other inflammatory arthritides but has never been tried in PsA. Combination csDMARDs have shown some superiority over single therapies but there are limited data and concerns about side effects. Early use of biologics has also been shown to be superior to methotrexate but these drugs are costly and not usually funded first line. However, if a short course of biologics can rapidly suppress inflammation allowing treatment to be withdrawn and response maintained on methotrexate, this may be a cost-effective model for early use.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT03739853) and EudraCT (2017-004542-24).
PubMed: 38826570
DOI: 10.1177/1759720X241240913 -
The Journal of Rheumatology Jun 2024To analyze the long-term survival of subcutaneous biosimilar TNFα-inhibitors (TNFi) compared to the originator molecules in patients with rheumatic diseases, and the...
OBJECTIVE
To analyze the long-term survival of subcutaneous biosimilar TNFα-inhibitors (TNFi) compared to the originator molecules in patients with rheumatic diseases, and the factors associated with drug discontinuation.
METHODS
Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of rheumatic patients on biological and targeted disease-modifying anti-rheumatic drugs. Patients who started etanercept or adalimumab from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific (inefficacy or adverse events) causes of discontinuation.
RESULTS
A total of 4162 patients received 4723 treatment courses (2991 courses of adalimumab and 1732 courses of etanercept), of which 722 (15.29%) were originator molecules and 4001 (84.71%) biosimilars. The originators were more frequently discontinued than biosimilars (53.32% and 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI: 0.75-0.95). Female sex, obesity and second or later treatment lines increased the risk of discontinuation, while disease duration and the use of concomitant methotrexate were associated to a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators.
CONCLUSION
No significant differences were found between treatmens in the longterm survival due to inefficacy or adverse events.
PubMed: 38825358
DOI: 10.3899/jrheum.2024-0001 -
RMD Open May 2024To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
PERFECTRA: a pragmatic, multicentre, real-life study comparing treat-to-target strategies with baricitinib versus TNF inhibitors in patients with active rheumatoid arthritis after failure on csDMARDs.
OBJECTIVE
To compare the effectiveness of a strategy administering baricitinib versus one using TNF-inhibitors (TNFi) in patients with rheumatoid arthritis (RA) after conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) failure in a real-life treat-to-target (T2T) setting.
METHODS
Patients with biological and targeted synthetic DMARD (b/tsDMARD) naïve RA with disease duration ≤5 years without contraindications to b/tsDMARD were randomised to either TNFi or baricitinib when csDMARD failed to achieve disease control in a T2T setting. Changes in clinical and patient-reported outcome measures (PROMs) were assessed at 12-week intervals for 48 weeks. The primary endpoint was non-inferiority, with testing for superiority if non-inferiority is demonstrated, of baricitinib strategy in the number of patients achieving American College of Rheumatology 50 (ACR50) response at 12 weeks. Secondary endpoints included 28-joint count Disease Activity Score with C reactive protein (DAS28-CRP) <2.6, changes in PROMs and radiographic progression.
RESULTS
A total of 199 patients (TNFi, n=102; baricitinib, n=97) were studied. Both study groups were similar. Baricitinib was both non-inferior and superior in achieving ACR50 response at week 12 (42% vs 20%). Moreover, 75% of baricitinib patients achieved DAS28-CRP <2.6 at week 12 compared with 46% of TNFi patients. On secondary outcomes throughout the duration of the study, the baricitinib strategy demonstrated comparable or better outcomes than TNFi strategy. Although not powered for safety, no unexpected safety signals were seen in this relatively small group of patients.
CONCLUSION
Up to present, in a T2T setting, patients with RA failing csDMARDs have two main strategies to consider, Janus Kinases inhibitor versus bDMARDs (in clinical practice, predominantly TNFi). The PERFECTRA study suggested that starting with baricitinib was superior over TNFi in achieving response at 12 weeks and resulted in improved outcomes across all studied clinical measures and PROMs throughout the study duration in these patients.
Topics: Humans; Purines; Sulfonamides; Arthritis, Rheumatoid; Pyrazoles; Azetidines; Male; Female; Middle Aged; Antirheumatic Agents; Aged; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Treatment Failure; Adult; Patient Reported Outcome Measures; Severity of Illness Index
PubMed: 38816210
DOI: 10.1136/rmdopen-2024-004291