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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 -
Drugs of Today (Barcelona, Spain : 1998) Sep 2021Pyoderma gangrenosum is a refractory disease characterized by chronic ulcers, presenting with central deep ulceration and undermined borders predominantly involving the...
Pyoderma gangrenosum is a refractory disease characterized by chronic ulcers, presenting with central deep ulceration and undermined borders predominantly involving the lower extremities. Oral prednisolone and/or cyclosporine has been considered to be a first line of therapy; however, there are still unmet needs for treatment. Recently, effects of adalimumab for pyoderma gangrenosum in 22 Japanese patients were examined in an open-label, multicenter study during a 26-week treatment period and a further 26-week extension period. Pyoderma gangrenosum area reduction 100 (PGAR 100, defined as complete skin re-epithelialization) response for the target ulcer was observed in 3 patients (13.6%) as early as week 6, and at week 26, 12 patients (54.5%) achieved the primary endpoint of PGAR 100. The mean percent change from baseline in target ulcer area was -63.8% at week 26. A physician's global assessment score of 0 (PGA 0) was achieved by 8 patients (36.4%), while PGA 0/1 (completely/almost clear) was achieved by 12 patients (54.5%) at week 26. Adverse events were reported by 18 patients, most commonly infections (n = 11) and serious adverse events (n = 4). These results suggest that adalimumab is effective and generally well tolerated in Japanese patients with pyoderma gangrenosum active ulcers.
Topics: Adalimumab; Humans; Pyoderma Gangrenosum
PubMed: 34586101
DOI: 10.1358/dot.2021.57.9.3293619 -
Clinical and Translational Science May 2020This study aimed at exploring the concentration-effect relationship of adalimumab and early adalimumab and anti-adalimumab antibody (AAA) levels in predicting primary... (Observational Study)
Observational Study
This study aimed at exploring the concentration-effect relationship of adalimumab and early adalimumab and anti-adalimumab antibody (AAA) levels in predicting primary nonresponse in a real-world pilot cohort of patients with ankylosing spondylitis. Thirty-one patients were included. The Ankylosing Spondylitis Disease Activity Score improved with increasing adalimumab trough level at week 12 and reached a major improvement with levels between 8 and 12 μg/mL. Moreover, weeks 4 and 2 adalimumab levels below 4.28 and 3.37 μg/mL were predictive of primary nonresponse (area under the curve (AUC) = 0.89, 0.88; P = 0.0003, P = 0.034, respectively). Week 4 AAA signal-to-noise levels were significantly higher among primary nonresponders, and the cutoff for primary nonresponse prediction was above 5.31 (AUC = 0.81; P = 0.004). Adalimumab trough levels in a range of 8-12 μg/mL are optimum to reach major improvement, and lower adalimumab with higher AAA levels at the early stage (week 4) predict primary nonresponse by supporting proactive monitoring to optimize adalimumab therapy.
Topics: Adalimumab; Adult; Antibodies; Antirheumatic Agents; Area Under Curve; Cohort Studies; Drug Resistance; Female; Humans; Male; Prognosis; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 31961477
DOI: 10.1111/cts.12738 -
BMC Immunology Dec 2021ABP501 is a biosimilar to Reference Adalimumab (HUMIRA®) produced by AMGEN. Adalimumab (ADA) has a marketing authorization for Crohn's disease, ulcerative colitis and...
BACKGROUND
ABP501 is a biosimilar to Reference Adalimumab (HUMIRA®) produced by AMGEN. Adalimumab (ADA) has a marketing authorization for Crohn's disease, ulcerative colitis and other inflammatory or autoimmune diseases. The aim of this study was to evaluate the LISA-TRACKER assays developed by Theradiag (France), for the monitoring of ABP501 and anti-ABP501 antibodies in human serum.
RESULTS
68 ABP501 clinical samples were measured with the LISA TRACKER Duo Adalimumab assay. LISA TRACKER has been validated as suitable for quantification of ABP501 in human serum samples. Accuracy of the LISA-TRACKER was measured using 3 human serum matrices spiked with known levels of biosimilar, 3 levels spanning the dynamic range. Percentages of recovery were ranged from 90 to 120% for biosimilar batch1, and between 93 and 105% for biosimilar batch2. The acceptance criteria (CV < 20%) were met for intra-run (from 3.8 to 16.5%) and inter-run imprecision (from 4.4 to 13.9%) including the two batches. All results were comprised within ± 20% from results, obtained with the kit and sample unexposed in order to evaluate stability of the sample, stability of the kit and consistency of the results. In any case, but two, all percentages of inhibition were > 50% for specificity. Specificity was tested with Biosimilar spiked samples, Biosimilar with Humira® spiked samples, and clinical samples from patients treated with adalimumab biosimilar. All of these samples were spiked with polyclonal antibodies directed against Humira®. Specificity inhibition and specificity detection steps were also part of the validation parameters. Reagents made with ABP501 gave similar results than reagents made with Humira® meeting acceptance criteria.
CONCLUSIONS
LISA-TRACKER ADA and anti-ADA assays are reliable for the monitoring of patients treated with ABP501.
Topics: Adalimumab; Biosimilar Pharmaceuticals; Colitis, Ulcerative; Drug Monitoring; Humans; Immunoassay
PubMed: 34953484
DOI: 10.1186/s12865-021-00473-1 -
Expert Opinion on Biological Therapy Oct 2019: Biosimilars represent great potential in cost saving and re-investment opportunities in healthcare and allow patients greater access to effective mAbs. Infliximab... (Review)
Review
: Biosimilars represent great potential in cost saving and re-investment opportunities in healthcare and allow patients greater access to effective mAbs. Infliximab biosimilars are successfully used in all indications for whom the reference product (RP) was approved. : In late 2018, adalimumab biosimilars will also be available in patients with inflammatory bowel disease (IBD). ABP501, BI 695501, GP2017, and SB5 have been approved by the EMA for the same indications of the reference product (RP, Humira®). Preclinical data show high similarity between all biosimilars and the RP. Clinical data in patients with rheumatoid arthritis and psoriasis also show no differences in terms of efficacy, safety, and immunogenicity. Data in IBD patients are still lacking. : Biosimilars of adalimumab appear to be clinically equivalent to the RP. Decisions based on choosing the ideal patient to receive or to be switched to a biosimilar of adalimumab, or choosing one biosimilar vs. another, or cross-switching among biosimilars remain the next challenge in the field of IBD.
Topics: Adalimumab; Antibodies, Monoclonal; Biosimilar Pharmaceuticals; Clinical Trials as Topic; Half-Life; Humans; Inflammatory Bowel Diseases; Infliximab
PubMed: 30601098
DOI: 10.1080/14712598.2019.1564033 -
The Lancet. Rheumatology Sep 2023An adalimumab biosimilar with an interchangeability designation could increase access to effective treatment for more patients. We aimed to assess the interchangeability... (Randomized Controlled Trial)
Randomized Controlled Trial
Multiple switching between the biosimilar adalimumab PF-06410293 and reference adalimumab in patients with active rheumatoid arthritis: a phase 3, open-label, randomised, parallel-group study.
BACKGROUND
An adalimumab biosimilar with an interchangeability designation could increase access to effective treatment for more patients. We aimed to assess the interchangeability of adalimumab biosimilar PF-06410293 (adalimumab-afzb) and reference adalimumab using a multi-switch study design.
METHODS
We did an open-label, randomised, parallel-group study at 61 community (n=29), hospital (n=12), and academic (n=20) sites in ten countries (Bulgaria, Bosnia and Herzegovina, Czech Republic, Lithuania, Poland, Russia, Serbia, South Africa, Ukraine, and USA). Eligible patients were aged 18-70 years and met the 2010 American College of Rheumatology-European League Against Rheumatism classification criteria for rheumatoid arthritis for at least 4 months with moderately to severely active rheumatoid arthritis, based on their physician's evaluation. Eligible patients had been receiving methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks before the first dose of study medication. All patients received subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) for 10 weeks before randomisation. At week 10, patients were randomly assigned (1:1) to either three switches between subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) and adalimumab-afzb (40 mg/0·8 mL [50 mg/mL] every 2 weeks; switching group), or continuous dosing with subcutanous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks; non-switching group) with stratification by bodyweight groups. Patients, investigators, and site personnel were not masked to treatment allocation. Primary endpoints were maximum observed serum concentration (C) and area under plasma concentration-time curve (AUC) during weeks 30-32 in the pharmacokinetic population. Interchangeability was based on geometric mean ratios and corresponding 90% CIs within prespecified equivalence margins of 80-125% for both primary endpoints. Safety was analysed in all patients who received at least one dose of adalimumab-afzb or reference adalimumab. This trial is registered with ClinicalTrials.gov, NCT04230213.
FINDINGS
Of the 569 patients assessed for eligibility between Jan 13, 2020, and June 22, 2021, 445 were enrolled, and 427 completed the first 10 weeks and were randomly assigned (213 to the switching group and 214 to the non-switching group). Participants had a median age of 56 years (IQR 46-63), 354 (83%) of 427 patients were women and 73 (17%) were men, and 422 (99%) were White. In the pharmacokinetic population (n=380), no clinically meaningful differences were observed in mean steady-state pharmacokinetic parameters between the switching and non-switching groups (geometric mean AUC 2237 μg × h/mL in the switching group and 2125 μg × h/mL in the non-switching group; C 8·21 μg/mL in the switching group and 8·00 μg/mL in the non-switching group). Geometric mean ratios and 90% CIs for AUC (105·31, 89·16-124·39) and C (102·56, 89·78-117·17) were within prespecified equivalence margins. No meaningful differences were observed in the proportion of patients who had serious adverse events (three [1%] of 213 patients in the switching group vs eight [4%] of 214 patients in the non-switching group), grade 3 or higher adverse events of special interest, discontinuations due to adverse events (eight [4%] vs nine [4%]), or immunogenic reactions in antidrug antibody-positive patients. No deaths were reported during the study.
INTERPRETATION
The risk of multiple switches between reference adalimumab and adalimumab-afzb with respect to diminished efficacy (using pharmacokinetics as a surrogate) or safety is not greater than the risk of using reference adalimumab alone.
FUNDING
Pfizer. VIDEO ABSTRACT.
Topics: Female; Humans; Male; Middle Aged; Adalimumab; Arthritis, Rheumatoid; Biosimilar Pharmaceuticals; Methotrexate
PubMed: 38251497
DOI: 10.1016/S2665-9913(23)00161-3 -
Ophthalmology Mar 2022
Comparative Study
Topics: Adalimumab; Drug-Related Side Effects and Adverse Reactions; Eye Infections; Humans; Infliximab; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Uveitis; Visual Acuity
PubMed: 34634363
DOI: 10.1016/j.ophtha.2021.09.025 -
Journal of Gastroenterology Sep 2020Anti-tumor necrosis factor (TNF)-α antibodies are effective therapeutic agents to treat inflammatory bowel disease (IBD). In the biologic era, the development of... (Comparative Study)
Comparative Study Review
Anti-tumor necrosis factor (TNF)-α antibodies are effective therapeutic agents to treat inflammatory bowel disease (IBD). In the biologic era, the development of immunogenicity has been a critical issue for secondary loss of response. The superiority of anti-TNF therapy in combination with immunomodulators (IMs) is well-established for infliximab (IFX) but less evident for adalimumab (ADA). To clarify the contribution of thiopurines to ADA-treated patients with Crohn's disease (CD), the deep remission of immunomodulator and adalimumab combination therapy for Crohn's disease (DIAMOND) studies provided the first randomized comparison of efficacy between ADA monotherapy and ADA with thiopurine. The results of the DIAMOND and DIAMOND2 studies revealed the appropriate ADA therapeutic strategy for immunosuppressant-naïve patients with active CD based on therapeutic drug monitoring, endoscopic findings and clinical issues regarding the use of thiopurines.
Topics: Adalimumab; Crohn Disease; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Immunologic Factors; Infliximab; Randomized Controlled Trials as Topic; Tumor Necrosis Factor Inhibitors
PubMed: 32661927
DOI: 10.1007/s00535-020-01702-x -
American Journal of Ophthalmology Feb 2024To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission.
PURPOSE
To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission.
DESIGN
Retrospective study.
METHODS
In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering.
RESULTS
Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04).
CONCLUSIONS
When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.
Topics: Humans; Female; Adult; Male; Adalimumab; Retrospective Studies; Inflammation; Uveitis; Recurrence; Vision Disorders; Treatment Outcome
PubMed: 37734639
DOI: 10.1016/j.ajo.2023.09.012 -
Medicine Jun 2021Adalimumab is used as a first-line biologic agent in the management of moderate-to-severe hidradenitis suppurativa (HS). The objective of the present study was to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adalimumab is used as a first-line biologic agent in the management of moderate-to-severe hidradenitis suppurativa (HS). The objective of the present study was to evaluate the efficacy and safety of adalimumab in patients with moderate-to-severe HS.
METHODS
We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Pooled estimates, namely standardized mean difference (SMD) and relative risk (RR), were calculated using random-effect model with trial sequential analysis. Small study effects were examined using the Doi plot. Certainty of evidence (CoE) was assessed using "The Grading of Recommendations Assessment, Development, and Evaluation" approach, and number-needed-to-treat (NNT) was calculated.
RESULTS
Five randomized controlled trials, involving 1014 patients, were included. We performed subgroup analysis of adalimumab administered subcutaneously both weekly and every other week. Adalimumab administered weekly was associated with better clinical response achievement (RR 1.76, 95% confidence interval [95% CI] 1.35-2.29; trial sequential analysis TSA-adjusted CI 1.01-3.08; CoE: low; NNT = 5) and a significant improvement in modified Sartorius score (SMD = -0.45, 95% CI = -0.76 to -0.13; CoE: very low; NNT = 10) and dermatology life quality index (DLQI) (SMD -0.47, 95% CI -0.61 to -0.32; CoE: low; NNT = 10). Nevertheless, adalimumab administered every other week showed an improvement only in modified Sartorius score. The pooled RRs of adverse events in both groups revealed no statistical significance when compared with the placebo.
CONCLUSIONS
Adalimumab administered weekly resulted in not only better clinical responses than placebo but also significantly improved disease severity and quality of life of patients with moderate-to-severe HS. Our study provides supporting evidence to the current guidelines and aids decision-making in the application of adalimumab in HS management.
Topics: Adalimumab; Adult; Antibodies, Monoclonal, Humanized; Case-Control Studies; Hidradenitis Suppurativa; Humans; Injections, Subcutaneous; Middle Aged; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 34087885
DOI: 10.1097/MD.0000000000026190