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Adverse events of anti-tumor necrosis factor α therapy in ankylosing spondylitis.

ABSTRACT: This study aims to investigate the prevalence of short-term and long-term adverse events associated with tumor necrosis factor-α (TNF-α) blocker treatment in Chinese Han patients suffering from ankylosing spondylitis (AS).The study included 402 Chinese Han AS patients treated with TNF-α blockers. Baseline data was collected. All patients were monitored for adverse events 2 hours following administration. Long-term treatment was evaluated at 8, 12, 52 and 104 weeks follow-up for 172 patients treated with TNF-α blockers.Short-term adverse events occurred in 20.15% (81/402), including rash (3.5%; 14/402), pruritus (1.2%; 5/402), nausea (2.2%; 9/402), headache (0.7%; 3/402), skin allergies (4.0%; 16/402), fever (0.5%; 2/402), palpitations (3.0%; 12/402), dyspnea (0.5%; 2/402), chest pain (0.2%; 1/402), [corrected] abdominal pain (1.0%; 4/402), hypertension (2.2%; 9/402), papilledema (0.5%; 2/402), laryngeal edema (0.2%; 1/402) and premature ventricular contraction (0.2%; 1/402). Long-term adverse events occurred in 59 (34.3%; 59/172) patients, including pneumonia (7.6%; 13/172), urinary tract infections (9.9%; 17/172), otitis media (4.7%; 8/172), tuberculosis are (3.5%; 6/172) [corrected], abscess (1.2%; 2/172), oral candidiasis (0.6%; 1/172), elevation of transaminase (1.7%; 3/172), anemia (1.2%; 2/172), hematuresis (0.6%; 1/172), constipation (2.3%; 4/172), weight loss (0.6%; 1/172), exfoliative dermatitis (0.6%; 1/172). CRP, ESR and disease duration were found to be associated with an increased risk of immediate and long-term adverse events (P<0.05). Long-term treatment with Infliximab was associated with more adverse events than rhTNFR-Fc (P<0.01).This study reports on the prevalence of adverse events in short-term and long-term treatment with TNF-α blocker monotherapy in Chinese Han AS patients. Duration of disease, erythrocyte sedimentation rate, and c-reactive protein serum levels were found to be associated with increased adverse events with anti-TNF-α therapy. Long-term treatment with Infliximab was associated with more adverse events than rhTNFR-Fc.

SUBMITTER: Tong Q

PROVIDER: S-EPMC4357466 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:IntroductionTumor necrosis factor (TNF) antagonists reduce the signs and symptoms of spondyloarthritides, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Our objective was to evaluate the effectiveness and safety of adalimumab, 40 mg every other week, for patients with AS or PsA and prior treatment with infliximab (IFX) and/or etanercept (ETN).MethodsBoth trials were 12-week, open-label studies with an optional extension period up to week 20. Patients were stratified by history of anti-TNF treatment, prior anti-TNF therapy received (IFX, ETN, or both), and reason for discontinuation of prior TNF antagonist. ETN was discontinued>or=3 weeks, and IFX was discontinued>or=2 months before the first adalimumab administration. Effectiveness at week 12 was evaluated by using observed standard-outcome measurements for AS and PsA.ResultsAt week 12 of adalimumab treatment, Bath Ankylosing Spondylitis Disease Activity Index 50 responses were achieved by 40.8% of 326 patients with AS who had received prior anti-TNF therapy and by 63.0% of 924 patients with AS who were naive to TNF antagonist. Observed response rates were generally greater for patients who discontinued the prior anti-TNF therapy because of loss of response or intolerance than for patients who discontinued because of lack of response. Median changes in swollen-joint count and in enthesitis score were similar in patients with and without prior TNF-antagonist treatment. Modified PsA response criteria were fulfilled by 71.2% of 66 patients with PsA, with prior exposure to TNF antagonists, and by 78.8% of 376 patients with no history of anti-TNF therapy. The percentages of patients with PsA attaining a Physician's Global Assessment of psoriasis of "Clear/Almost clear" increased from 33.3% to 61.0% for patients with prior IFX and/or ETN treatment and from 34.6% to 69.7% for patients without anti-TNF therapy. The median change in the Nail Psoriasis Severity Index was -6 for both groups. In both studies, patterns of adverse events were similar for patients with and without prior anti-TNF therapy and were consistent with the known safety profile of adalimumab.ConclusionsPatients with AS or PsA previously treated with IFX and/or ETN experienced clinically relevant improvements of their diseases after 12 weeks of adalimumab.Trial registrationsClinicalTrials.gov NCT00478660 and NCT00235885.

Project description:AIM:To study the type and frequency of adverse events associated with anti-tumor necrosis factor (TNF) therapy and evaluate for any serologic and genetic associations. METHODS:This study was a retrospective review of patients attending the inflammatory bowel disease (IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure. RESULTS:Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients (21%) were found to have adverse events to an anti-TNF-α agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the anti-TNF agent. In total: n = 66 (5%) infusion reactions; n = 49 (4%) allergic/serum sickness reactions; n = 19 (1.5%) lupus-like reactions, n = 52 (4%) rash, n = 18 (1.4%) infections. In Crohn's disease, IgA ASCA (P = 0.04) and IgG-ASCA (P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions (P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT (Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event. CONCLUSION:Our study shows 1 in 5 IBD patients experience an adverse event to anti-TNF therapy with novel serologic, genetic , and pathways associations.

Project description:To study the effect of tumor necrosis factor ? (TNF?) inhibitors on progressive spinal damage in patients with ankylosing spondylitis (AS).All AS patients meeting the modified New York criteria who had been monitored prospectively and had at least 2 sets of spinal radiographs a minimum of 1.5 years apart were included in the study (n=334). The patients received standard therapy, which included nonsteroidal antiinflammatory drugs and TNF? inhibitors. Radiographic severity was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Patients with a rate of AS progression that was ?1 mSASSS unit/year were considered progressors. Univariable and multivariable regression analyses were done. Propensity score matching and sensitivity analysis were performed. A zero-inflated negative binomial (ZINB) model was used to analyze the effect of TNF? inhibitors on the change in the mSASSS with varying followup periods. Potential confounders, such as disease activity (as assessed by the Bath Ankylosing Spondylitis Disease Activity Index), the erythrocyte sedimentation rate, C-reactive protein level, HLA-B27 positivity, sex, age at onset, smoking burden (number of pack-years), and baseline damage, were included in the model.TNF? inhibitor treatment was associated with a 50% reduction in the odds of progression, with an odds ratio (OR) of 0.52 (95% confidence interval [95% CI] 0.30-0.88, P=0.02). Patients with a delay of >10 years in starting therapy were more likely to experience progression as compared to those who started earlier (OR 2.4 [95% CI 1.09-5.3], P=0.03). In the ZINB model, the use of TNF? inhibitors significantly reduced disease progression when the gap between radiographs was >3.9 years. The protective effect of TNF? inhibitors was stronger after propensity score matching.Treatment with TNF? inhibitors appears to reduce radiographic progression in AS patients, especially with early initiation and with longer duration of followup.

Project description:ImportanceTumor necrosis factor inhibitors (TNFis) have revolutionized the management of ankylosing spondylitis (AS); however, the lack of notable clinical responses in approximately one-half of patients suggests important heterogeneity in treatment response. Identifying patients likely to respond or not respond to TNFis could provide opportunities to personalize treatment strategies.ObjectiveTo develop models of the probability of short-term response to TNFi treatment in individual patients with active AS.Design, setting, and participantsThis is a retrospective cohort study using data of the TNFi group (ie, treatment group) from 10 randomized clinical trials (RCTs) of TNFi treatment among patients with active AS, conducted from 2002 to 2016. Participants were adult patients with active AS who failed nonsteroidal anti-inflammatory drugs. Included RCTs were phase 3 and 4 studies that assessed the efficacy of an originator TNFi at week 12 and/or week 24, either compared with placebo or an antirheumatic drug. The cohort was divided into a training and a testing set. Data analysis was conducted from July 1, 2019, to November 30, 2020.ExposuresAll included patients received an originator TNFi for at least 12 weeks.Main outcomes and measuresOutcomes included major response and no response based on the change of AS Disease Activity Score at 12 weeks. Machine learning algorithms were applied to estimate the probability of having major response and no response for individual patients.ResultsThe study included 1899 participants from 10 trials. The training set included 1207 individuals (mean [SD] age, 39 [12] years; 908 [75.2%] men), of whom 407 (33.7%) had major response and 414 (34.3%) had no response. In the reduced logistic regression models, accuracy was 0.74 for major response and 0.75 for no response. The probability of major response increased with higher C-reactive protein (CRP) level, patient global assessment (PGA), and Bath AS Disease Activity Index (BASDAI) question 2 score and decreased with higher body mass index (BMI) and Bath AS Functional Index (BASFI) score. The probability of no response increased with age and BASFI score, and decreased with higher CRP level, BASDAI question 2 score, and PGA. In the testing set (692 participants; mean [SD] age, 38 [11] years; 533 [77.0%] men), models demonstrated moderate to high accuracy.Conclusions and relevanceIn this cohort study, the probability of initial response to TNFi was predicted from baseline variables, which may facilitate personalized treatment decision-making.

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Adverse events of anti-tumor necrosis factor α therapy in ankylosing spondylitis.

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