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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 -
Scientific Reports Dec 2023Although biologics have their own characteristics, there are no clear criteria for selecting them to treat the patients with rheumatoid arthritis. To assist in selecting...
Although biologics have their own characteristics, there are no clear criteria for selecting them to treat the patients with rheumatoid arthritis. To assist in selecting biologics, we investigated the retention rates of biologics at our institution. We examined retention rates, and reasons for dropout for biologics in 393 cases and 605 prescriptions (of which 378 prescriptions were as naive) at our hospital since October 2003. Throughout the entire course of the study, etanercept (ETN) was the most frequently used biologic, followed by adalimumab (ADA) and tocilizumab (TCZ). When narrowed down to the later period from 2010, ETN was still the most used, followed by TCZ and abatacept (ABT). When the retention rates were compared in biologic naive patients, the retention rates were TCZ, ABT, ETN, certolizumab pegol (CZP), golimumab (GLM), infliximab (IFX), and ADA, in that order. The retention rates were better with the first use of each biologic. The main reasons for dropout were primary ineffectiveness, secondary ineffectiveness, and infection. ETN was the most used biologic in our hospital, with an increasing trend toward the use of non-TNF inhibitors. Retention rates were higher in non-TNF inhibitors.
Topics: Humans; Antirheumatic Agents; Biological Products; Treatment Outcome; Arthritis, Rheumatoid; Etanercept; Adalimumab; Infliximab; Abatacept
PubMed: 38040839
DOI: 10.1038/s41598-023-48537-z -
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 -
Actas Dermo-sifiliograficas Oct 2023Hidradenitis suppurativa (HS) is a chronic inflammatory entity characterized by the appearance of multiple nodules, abscesses, and fistulas, predominantly in apocrine... (Review)
Review
Hidradenitis suppurativa (HS) is a chronic inflammatory entity characterized by the appearance of multiple nodules, abscesses, and fistulas, predominantly in apocrine regions. In addition to its dermatological involvement, it is associated with multiple systemic comorbidities. Its treatment is combined: topical pharmacological, systemic pharmacological and surgical. Regarding biologic or small molecule drugs, currently only adalimumab is approved. A narrative review of the literature on biological or small molecule drugs used in the treatment of hidradenitis suppurativa is presented. The arsenal we found is large, with multiple targets: inhibitors of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-17, IL-23, IL-1, inhibitors of the janus kinase (JAK) pathway, and multiple other drugs in study. New prospective studies and comparative trials are needed to analyze the effectiveness and safety of these treatments, in an entity with a promising future.
Topics: Humans; Hidradenitis Suppurativa; Prospective Studies; Adalimumab; Tumor Necrosis Factor-alpha; Biological Products
PubMed: 37211274
DOI: 10.1016/j.ad.2023.05.015 -
BMC Ophthalmology May 2023To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU). (Meta-Analysis)
Meta-Analysis
PURPOSE
To compare the efficacy and safety of infliximab with that of adalimumab in the treatment of non-infectious uveitis (NIU).
METHODS
We searched for relevant studies in the PubMed, Embase, ClinicalTrials.gov, Cochrane Library databases, Grey Matters, Grey Literature Report, OpenGrey, China National Knowledge Infrastructure (CNKI), and Wan Fang databases up to September 2022. The incidences of complete remission of inflammation, response to therapy, adverse events and corticosteroid-sparing effect were evaluated.
RESULTS
Eleven clinical trials covering 1459 NIU patients were included. Complete remission of inflammation after therapy was achieved in 161 (37.5%) patients in the infliximab group and 151 (39.6%) patients in the adalimumab group. These two groups were not significantly different (P = 0.37). Four studies reported response to anti-TNF therapy involving 449 patients, of whom 241/272 (88.6%) treated with infliximab and 153/177 (86.4%) treated with adalimumab achieved partial or complete remission of inflammation. No significant difference was observed between the two cohorts in terms of response to therapy (P = 0.86). There was no significant difference between infliximab and adalimumab with regard to corticosteroid-sparing effect (P = 0.58). The pooled effect size (P = 0.001) showed a statistically significant difference, with the incidence of adverse events being 17.91% for infliximab and 12.12% for adalimumab.
CONCLUSION
Our systematic review and meta-analysis of 11 studies suggests that infliximab and adalimumab have similar therapeutic efficacy and corticosteroid-sparing effect in patients with NIU. However, adalimumab has a marginal advantage over infliximab in terms of adverse events. Large-scale RCTs with a longer follow-up are required to further evaluate these two anti-TNF-α agents in patients with NIU.
Topics: Humans; Adalimumab; Infliximab; Antibodies, Monoclonal; Tumor Necrosis Factor Inhibitors; Antibodies, Monoclonal, Humanized; Tumor Necrosis Factor-alpha; Uveitis; Inflammation
PubMed: 37248486
DOI: 10.1186/s12886-023-02987-1 -
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 -
International Journal of Molecular... Aug 2022Hidradenitis suppurativa, also known as acne inversa, is a chronic, progressive, debilitating, recurrent inflammatory skin disease characterized by the occurrence of... (Review)
Review
Hidradenitis suppurativa, also known as acne inversa, is a chronic, progressive, debilitating, recurrent inflammatory skin disease characterized by the occurrence of very severe, persistent, painful nodules, abscesses, and fistulas, most commonly found in the skin folds of the axilla, groin, gluteal, and perianal areas. Treatment is rather difficult and typically requires the use of multiple modalities. Regardless of the presence of several therapeutic options, treatment often turns out to be ineffective or poorly selected concerning the clinical picture of the disease. Thus, the search for new biologics and other target treatments of hidradenitis suppurativa is ongoing. The safety and efficacy of adalimumab, still the only U.S. Food and Drug Administration approved biologic in the hidradenitis suppurativa treatment, paved the way for new drugs to be compared with it. Several more drugs with new immunological targets are currently under investigation for the treatment of acne inversa. The aim of the article was to present the current and future targets of acne inversa treatment, simultaneously providing insights into the molecular pathomechanisms of the disease.
Topics: Adalimumab; Hidradenitis Suppurativa; Humans; Immunomodulating Agents; United States; United States Food and Drug Administration
PubMed: 36077114
DOI: 10.3390/ijms23179716