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Journal of Managed Care & Specialty... Aug 2023Real-world data on persistence on ustekinumab and adalimumab among bio-experienced patients with Crohn's disease (CD) are limited. To compare treatment persistence and...
Real-world data on persistence on ustekinumab and adalimumab among bio-experienced patients with Crohn's disease (CD) are limited. To compare treatment persistence and describe switching, restart, and dose titration among bio-experienced patients with CD initiated on ustekinumab or adalimumab. IBM MarketScan Commercial Database was used to identify bio-experienced adults with CD who were assigned to either the ustekinumab or adalimumab cohort based on the agent first initiated (index date) after September 23, 2016. Cohorts were balanced using inverse probability of treatment weights-average treatment effect on treated. Persistence on index agent (absence of exposure gap > 120 days for ustekinumab or > 60 days for adalimumab), persistence while corticosteroid-free, and persistence while receiving monotherapy were assessed at 12 months after index date and compared between cohorts using weighted Kaplan-Meier and Cox proportional hazards model analyses. Among 903 patients in the ustekinumab cohort and 525 patients in the adalimumab cohort, baseline characteristics were balanced after weighting. At 12 months post-index, ustekinumab was associated with higher persistence (80.1% vs 64.6%; hazard ratio = 2.02 [95% CI = 1.60-2.56]; < 0.001) and persistence while receiving monotherapy (51.6% vs 40.0%; 1.51 [1.28-1.78]; < 0.001) vs adalimumab. Persistence while corticosteroid-free was similar in the ustekinumab vs adalimumab cohort (50.1% vs 48.2%; 1.19 [1.00-1.41]; = 0.0516). This retrospective real-world study demonstrated that among bio-experienced patients with CD, initiation of ustekinumab was associated with better persistence at 12 months of follow-up, including persistence while receiving monotherapy, compared with adalimumab. This study was funded by Janssen Scientific Affairs, LLC. Drs Zhao, Ding, and Kachroo are employees of Janssen Scientific Affairs, LLC, and stockholders of Johnson & Johnson. Dr Manceur, Mr Lefebvre, Ms Zhdanava, and Mr Pilon are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study and article. Mr Holiday was an employee of Analysis Group, Inc., at the time of study conduct.
Topics: Adult; Humans; Adalimumab; Crohn Disease; Ustekinumab; Retrospective Studies
PubMed: 37523319
DOI: 10.18553/jmcp.2023.29.8.907 -
Kidney360 Mar 2023This renal biopsy study documents clinical renal dysfunction and pathologic lesions encountered in patients after anti-TNF therapy and compares them with similar...
KEY POINTS
This renal biopsy study documents clinical renal dysfunction and pathologic lesions encountered in patients after anti-TNF therapy and compares them with similar patients without treatment. This study highlights the spectrum of autoimmune, serologic, and other kidney adverse effects of anti-TNF therapy. Unrelated active or chronic renal lesions including amyloidosis secondary to the underlying systemic inflammatory states may be observed.
BACKGROUND
Anti-TNF inhibitors, as biological agents, are used in autoimmune inflammatory states, rheumatoid arthritis (RA), psoriatic arthritis (PA), and Crohn disease. They can induce autoimmune serologic responses and clinical disorders, including systemic vasculitis and lupus-like diseases, affecting the kidney.
METHODS
Retrospective analysis of clinicopathologic features of kidney disease after anti-TNF therapy (treatment group) from our renal biopsy files from 2000 to 2018 is conducted and compared with 106 patients without therapy (control group).
RESULTS
Forty-eight patients using anti-TNF agents had renal biopsies: RA in 30, PA six, Crohn disease six, RA and PA one, RA and Crohn disease one, and others four. Twenty received etanercept, 15 adalimumab, eight infliximab, and five two forms of agents manifesting new-onset nephritic syndrome or CKD, 17 with AKI and 16 nephrotic syndrome, with recent ANCA and/or lupus serology. The renal lesions were crescentic GN in eight, pauci-immune–type in five, and ANCA+ in five. Lupus or lupus-like nephritis was seen in six: International Society of Nephrology/Renal Pathology Society 2018 class II—2, class V—2, class III+V—1, and class IV+V—1, and concurrent fibrillary GN, scleroderma/thrombotic microangiopathy (TMA), and amyloidosis in three. Renal lesions unrelated to anti-TNF therapy or underlying autoimmune disease were noted in 23 patients (, diabetic nephropathy, interstitial nephritis, acute tubular injury, infection-related GN); immunoglobulin A nephropathy, renal sarcoidosis, and amyloid A amyloidosis were noted in five patients. TMA was recognized in five patients, one associated with scleroderma and one anti-phospholipid antibodies, and two had nephrotic syndrome secondary to podocytopathy. The control group was similar with higher number of immune-mediated GN, interstitial nephritis, and amyloidosis.
CONCLUSION:
The renal lesions during anti-TNF therapy have an autoimmune basis such as ANCA and lupus or lupus-like disease, correlated with new-onset serology, while others were similar to those observed in the control group. Renal biopsy findings integrated with clinical features and therapy can identify the underlying pathophysiologic process for appropriate management.
Topics: Tumor Necrosis Factor Inhibitors; Infliximab; Adalimumab
PubMed: 36706240
DOI: 10.34067/KID.0000000000000063 -
Pediatric Rheumatology Online Journal Mar 2023Adalimumab in combination with other disease-modifying antirheumatic drugs (DMARD) such as methotrexate has a proven efficacy in the management of paediatric...
BACKGROUND
Adalimumab in combination with other disease-modifying antirheumatic drugs (DMARD) such as methotrexate has a proven efficacy in the management of paediatric non-infectious uveitis. However, many children experience significant intolerance to methotrexate while on this combination, leaving a dilemma for clinicians for choosing the subsequent therapeutic roadmap. Continuation of adalimumab monotherapy might be an alternative feasible option under such settings. This study aims to investigate the efficacy of adalimumab monotherapy in paediatric non-infectious uveitis.
METHODS
Children with non-infectious uveitis on adalimumab monotherapy (from August 2015 to June 2022) following intolerance to accompanying methotrexate or mycophenolate mofetil were included in this retrospective study. Data were collected at the initiation of adalimumab monotherapy and at three monthly intervals until the last visit. The primary outcome was to evaluate disease control on adalimumab monotherapy as determined by the proportion of patients who had less than a 2-step worsening in uveitis (as per SUN score) and no additional systemic immunosuppression during follow-up. Secondary outcome measures were visual outcome, complications and side-effect profile of adalimumab monotherapy.
RESULTS
Data was collected for 28 patients (56 eyes). The most common uveitis type and course were anterior and chronic uveitis respectively. Juvenile idiopathic arthritis-associated uveitis was the most common underlying diagnosis. During the study period, 23 (82.14%) of the study subjects met the primary outcome. On Kaplan-Meier survival analysis 81.25% (95% CI; 60.6-91.7%) children maintained remission at 12 months on adalimumab monotherapy.
CONCLUSION
Continuation of adalimumab monotherapy is an effective therapeutic option for the treatment of non-infectious uveitis in children who are intolerant to the combination of adalimumab and methotrexate or mycophenolate mofetil.
Topics: Humans; Child; Adalimumab; Methotrexate; Mycophenolic Acid; Retrospective Studies; Uveitis; Antirheumatic Agents
PubMed: 36864437
DOI: 10.1186/s12969-023-00794-y -
BMJ Case Reports Jan 2022Vasculitis and other autoimmune conditions are known complications of tumour necrosis factor alpha (TNF-α) inhibitor use. By definition, TNF-α inhibitor induced...
Vasculitis and other autoimmune conditions are known complications of tumour necrosis factor alpha (TNF-α) inhibitor use. By definition, TNF-α inhibitor induced vasculitis is a secondary systemic vasculitis. However, its phenotype is varied and can present as an isolated vasculitic neuropathy. This presents a diagnostic challenge as the gold standard for diagnosis of a vasculitic neuropathy is a peripheral nerve biopsy that meets predefined histopathological criteria. Given the poor sensitivity of the peripheral nerve biopsy, it is important that clinicians take a good history and maintain a high index of suspicion, as this is a treatable iatrogenic condition. Here we present a case of adalimumab-induced sensory vasculitic neuropathy, treated according to the Peripheral Nerve Society guideline for non-systemic vasculitic neuropathy, given her disease phenotype.
Topics: Adalimumab; Biopsy; Female; Humans; Peripheral Nervous System Diseases; Systemic Vasculitis; Vasculitis
PubMed: 35039360
DOI: 10.1136/bcr-2021-246401 -
Drug Design, Development and Therapy 2021Biologic drugs have revolutionized the treatment of psoriasis and other rheumatological diseases. In recent years, many biosimilar agents that are highly similar in... (Review)
Review
Biologic drugs have revolutionized the treatment of psoriasis and other rheumatological diseases. In recent years, many biosimilar agents that are highly similar in structure and function to their originator products have been developed, including the tumor necrosis factor-alpha antagonist adalimumab. The considerably lower cost of these products has greatly cut the economic burden of the patients and increased the accessibility of biologic therapies worldwide. The US Food and Drug Administration and/or the European Medicines Agency have approved eight biosimilars of adalimumab (ABP 501/BI 695501/SB5/GP2017/FKB327/MSB11022/PF-06410293/CT-P17) for the treatment of psoriasis, and others are under review. Given that these agents showed pharmacokinetic, efficacy, safety, and immunogenicity profiles comparable to those of the originator, adalimumab biosimilars were licensed for all indications approved for reference adalimumab based on extrapolation; however, some of the equivalence studies were only conducted in one or two disease populations. This review discusses the bioequivalence of adalimumab biosimilars as demonstrated by various clinical trials, the extrapolation of indications, guidance and policies of the EU and US on interchangeability (nonmedical switching/automatic substitution) between biosimilars and originators, and the real-life practices of switching from reference adalimumab to the respective biosimilars. Further data from real-world studies and post-marketing analyses are needed better to address the efficacy and safety of the transition strategy.
Topics: Adalimumab; Biosimilar Pharmaceuticals; Humans; Psoriasis; Therapeutic Equivalency; Tumor Necrosis Factor Inhibitors
PubMed: 34267501
DOI: 10.2147/DDDT.S317382 -
Medicina (Kaunas, Lithuania) Sep 2020The shared pathogenesis of psoriasis and atherosclerosis may be determined by assaying the levels of endothelial activation molecules. This study aimed at evaluating...
The shared pathogenesis of psoriasis and atherosclerosis may be determined by assaying the levels of endothelial activation molecules. This study aimed at evaluating vascular cell adhesion molecule 1 (VCAM-1) and E-selectin serum concentrations, and atherosclerosis severity in patients with plaque psoriasis. It also aimed to determine the effects of methotrexate/adalimumab treatment for 12 weeks on the plasma levels of the aforementioned molecules. The study included 34 psoriasis patients (17 treated with methotrexate and 17 treated with adalimumab) and eight controls. The 10-year risk of a fatal cardiovascular disease, body mass index, Psoriasis Area and Severity Index, and body surface area were calculated for each subject. VCAM-1 and E-selectin levels were determined via an enzyme-linked immunosorbent assay at baseline and after 12 weeks. Baseline E-selectin and VCAM-1 levels were higher in the adalimumab group than in the methotrexate and control groups. VCAM-1 levels decreased in the adalimumab ( = 0.02) and methotrexate groups ( = 0.008), while E-selectin levels decreased in the methotrexate group ( = 0.004). The results indicate a correlation between systemic psoriasis treatment and E-selectin and VCAM-1 plasma concentrations, which may be associated with the risk of cardiovascular disease development.
Topics: Adalimumab; Biomarkers; Cardiovascular Diseases; E-Selectin; Humans; Methotrexate; Psoriasis; Vascular Cell Adhesion Molecule-1
PubMed: 32942670
DOI: 10.3390/medicina56090473 -
PloS One 2022The adalimumab biosimilars FKB327 and GP2017 were approved for the therapy of patients with inflammatory bowel disease (IBD). Relatively few prospective studies with... (Observational Study)
Observational Study
OBJECTIVE
The adalimumab biosimilars FKB327 and GP2017 were approved for the therapy of patients with inflammatory bowel disease (IBD). Relatively few prospective studies with biosimilar adalimumab in patients with IBD have been published. The aim of this prospective observational study was to evaluate the effectiveness and safety of the biosimilar adalimumab.
MATERIAL AND METHODS
Adalimumab biosimilars FKB327 (Hulio®) and GP2017 (Hyrimoz®) were indicated to 50 naive patients in terms of biological therapy with Crohn's disease (CD) or ulcerative colitis (UC). Effectiveness of therapy was evaluated via the Crohn's Disease Activity Index [CDAI] or the Mayo Scoring System [MSS] in patients with CD or UC, respectively, before and after 12 weeks. Additional goals were to evaluate weight changes, laboratory tests and complications or adverse events of this therapy.
RESULTS
In CD patients, remission (CDAI <150) was achieved in 73.5% of cases, partial response (≥70-point decrease in CDAI score from baseline) in 11.8%, no response in 11.8% and 2.9% patients discontinued therapy. In UC patients, remission (total score on partial Mayo index ≤2 points) was achieved only in 18.8% of cases, partial response (≥2-point decrease in partial Mayo score from baseline) in 43.8%, no response in 25.0% and 12.5% patients discontinued therapy. There were statistically significant improvements in CDAI, MSS, haemoglobin, fecal calprotectin, albumin and CRP serum levels after 12 weeks of therapy. Seven adverse events were identified, three of which resulted in therapy being discontinued.
CONCLUSIONS
This prospective observational study proved the effectiveness of the adalimumab biosimilars FKB327 and GP2017 in IBD.
Topics: Adalimumab; Biosimilar Pharmaceuticals; Colitis, Ulcerative; Crohn Disease; Humans; Inflammatory Bowel Diseases; Prospective Studies; Remission Induction; Treatment Outcome
PubMed: 35939424
DOI: 10.1371/journal.pone.0271299 -
Gastroenterology Jun 2022Dose-optimization strategies for biologic therapies in Crohn's disease (CD) are not well established. The SERENE CD (Study of a Novel Approach to Induction and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Dose-optimization strategies for biologic therapies in Crohn's disease (CD) are not well established. The SERENE CD (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Crohn's Disease) trial evaluated higher vs standard adalimumab induction dosing and clinically adjusted (CA) vs therapeutic drug monitoring (TDM) maintenance strategies in patients with moderately to severely active CD.
METHODS
In this phase 3, randomized, double-blind, multicenter trial, eligible adults (Crohn's Disease Activity Index score of 220-450, endoscopic evidence of mucosal inflammation, and previous failure of standard therapies) were randomized to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3; n = 308) or standard induction regimen (adalimumab 160 mg at week 0 and 80 mg at week 2; n = 206) followed by 40 mg every other week from week 4 onward. Co-primary end points included clinical remission at week 4 and endoscopic response at week 12. At week 12, patients were re-randomized to maintenance therapy optimized by Crohn's Disease Activity Index and C-reactive protein (CA; n = 92) or serum adalimumab concentrations and/or clinical criteria (TDM; n = 92); exploratory end points were evaluated at week 56.
RESULTS
Similar proportions of patients receiving higher induction regimen and standard induction regimen achieved clinical remission at week 4 (44% in both; P = .939) and endoscopic response at week 12 (43% vs 39%, respectively, P = .462). Week 56 efficacy was similar between CA and TDM. Safety profiles were comparable between dosing regimens.
CONCLUSIONS
Higher induction regimen was not superior to standard induction regimen, and CA and TDM maintenance strategies were similarly efficacious. Adalimumab therapy was well tolerated, and no new safety concerns were identified. (ClinicalTrials.gov, Number: NCT02065570).
Topics: Adalimumab; Adult; C-Reactive Protein; Crohn Disease; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Remission Induction; Treatment Outcome
PubMed: 35122766
DOI: 10.1053/j.gastro.2022.01.044 -
British Journal of Clinical Pharmacology Nov 2020Adalimumab-adbm is a monoclonal antibody developed as a biosimilar to adalimumab (Humira, AbbVie Inc.). The key objectives of this study were using a population...
Population pharmacokinetics of adalimumab biosimilar adalimumab-adbm and reference product in healthy subjects and patients with rheumatoid arthritis to assess pharmacokinetic similarity.
AIMS
Adalimumab-adbm is a monoclonal antibody developed as a biosimilar to adalimumab (Humira, AbbVie Inc.). The key objectives of this study were using a population pharmacokinetic (PPK) approach to assess pharmacokinetic (PK) similarity between adalimumab-adbm and Humira in patients with active rheumatoid arthritis (RA), to quantify the effects of potential covariates on adalimumab PK and to assess the impact of switching treatment from Humira to adalimumab-adbm on PK.
METHODS
A PPK model was firstly developed using intensive PK data from the phase-1 study in healthy subjects (NCT02045979). PPK models were developed separately for phase-3 base study (NCT02137226) and its extension study (NCT02640612) in patients with active RA.
RESULTS
PPK models were developed for adalimumab from adalimumab-adbm and Humira treatment in healthy subjects and RA patients. Weight and anti-drug antibodies were found to be important predictors of adalimumab clearance. Adalimumab PK was similar between adalimumab-adbm and Humira. The estimated effect of Humira on clearance, relative to the adalimumab-adbm, was 1.02 (i.e., Humira has 0.02 greater clearance). Similarly, the effect of treatment arms (switching) on clearance was estimated to be 1.00 and 0.997 for Humira:Humira:BI and Humira:BI:BI arms, respectively, relative to the BI:BI:BI arm (BI refers to adalimumab-adbm) in the phase-3 extension study.
CONCLUSION
PK similarity between adalimumab-adbm and Humira in patients with active RA was demonstrated using PPK approach. Adalimumab PK was also similar when switching treatment from Humira to adalimumab-adbm at either week 24 or 48.
Topics: Adalimumab; Antirheumatic Agents; Arthritis, Rheumatoid; Biosimilar Pharmaceuticals; Double-Blind Method; Healthy Volunteers; Humans; Therapeutic Equivalency
PubMed: 32363771
DOI: 10.1111/bcp.14330 -
Dermatology (Basel, Switzerland) 2023Ten-year survival and retention rate data on biologics are extremely limited, and there is a need to evaluate these metrics based on real-world data as well as on the...
BACKGROUND
Ten-year survival and retention rate data on biologics are extremely limited, and there is a need to evaluate these metrics based on real-world data as well as on the results of clinical studies.
OBJECTIVE
The objective of this study was to assess the long-term survival rates of adalimumab and infliximab in real-life practice.
METHODS
This study is based on data from the Turkish Psoriasis Registry and the digital records of the Medical School of Bezmialem Vakif University. Baseline data including demographic characteristics, duration of treatment, use of combination treatments, modified regimens, and reasons for treatment termination were extracted.
RESULTS
In total, 404 patients (228 on adalimumab and 176 on infliximab) treated between July 1, 2005, and December 31, 2020, were identified. The retention rate was 7.4% for infliximab and 3.5% for adalimumab after 10 years (p = 0.85).
CONCLUSIONS
The efficacy of infliximab and adalimumab diminishes over time. There were no significant differences in the retention rate between the two drugs, but the survival time was longer for infliximab according to Kaplan-Meier analysis.
Topics: Humans; Adalimumab; Infliximab; Psoriasis; Etanercept; Treatment Outcome
PubMed: 36871548
DOI: 10.1159/000529964