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Autoimmunity Reviews Apr 2018Relapses upon corticosteroids tapering and immunosuppressive agents are frequent in Takayasu arteritis (TA). Interleukin-6 is highly involved in physiopathology of TA.... (Review)
Review
BACKGROUND
Relapses upon corticosteroids tapering and immunosuppressive agents are frequent in Takayasu arteritis (TA). Interleukin-6 is highly involved in physiopathology of TA. Many reports showed efficacy of tocilizumab (TCZ) in refractory TA cases. We report four cases and an updated literature review on the TCZ efficacy and safety in patients with TA.
METHODS
Patients with TA defined by ACR 1990 criteria were included. Clinical, biological and imaging data were retrospectively reported. Disease activity was analyzed before TCZ and during the follow-up. Medline database was searched for systematic literature review.
RESULTS
One hundred and five patients (median age 28years [22-38]) were included, mostly refractory cases (76 patients, 72%). Median TCZ duration was 12months [6-20]. Among 105 patients, 90 patients (85.7%) had an initial clinical response within three months [3-6] and 43/66 patients (65.2%) had a radiological improvement. Only seven patients (9%) showed relapse on therapy. Corticosteroid dose reduction was obtained in 75/83 patients (90.4%). Relapse after TCZ discontinuation was observed in six patients (46%), with a median time of five months [2-9]. Twenty-four side-effects were noted in 18 patients (18%), with TCZ interruption in seven cases (7%): 10 infections, five cytopenia, six hepatitis, one pancreatitis, one cutaneous rash and one breast cancer.
CONCLUSIONS
This review confirms that TCZ is safe and effective in refractory cases of TA and TCZ is a corticosteroid-sparing therapy in patients with or without previous TNFα blockers therapy. However relapses after TCZ discontinuation are frequent.
Topics: Adolescent; Adult; Antibodies, Monoclonal, Humanized; Female; Humans; Middle Aged; Retrospective Studies; Takayasu Arteritis; Treatment Outcome; Young Adult
PubMed: 29427826
DOI: 10.1016/j.autrev.2017.11.026 -
Autoimmunity Reviews Mar 2023Takayasu arteritis (TAK) refractory to conventional disease-modifying anti-rheumatic drugs (DMARDs) is commonly treated with biologic DMARDs such as tocilizumab or tumor... (Meta-Analysis)
Meta-Analysis Review
Takayasu arteritis (TAK) refractory to conventional disease-modifying anti-rheumatic drugs (DMARDs) is commonly treated with biologic DMARDs such as tocilizumab or tumor necrosis factor-alpha inhibitors (TNFi). The 2021 American College of Rheumatology (ACR) recommendations preferred TNFi to tocilizumab. Therefore, we conducted a systematic review with meta-analysis to assess the evidence base for tocilizumab in TAK by updating a previous systematic review on DMARDs in TAK through searches on MEDLINE, Pubmed Central, Scopus, major international Rheumatology conference abstracts, and clinical trial databases from January 2021 to November 2022. Thirty-five studies involving 1082 TAK [one randomized controlled trial (RCT), eleven controlled and twenty-one uncontrolled studies, most of moderate to high quality] had evaluated tocilizumab in TAK. The RCT of tocilizumab versus placebo failed to meet its primary end-point of superiority of tocilizumab on an intention-to-treat analysis (hazard ratio 0.41, 95%CI 0.15-1.10) but successfully met the secondary end-point of superiority on per-protocol analysis (hazard ratio 0.34, 95%CI 0.11-1.00). A meta-analysis of six studies identified similar rates of clinical remission [risk ratio (RR) tocilizumab vs TNFi 1.03, 95%CI 0.91-1.17)], angiographic stabilization (RR 1.00, 95%CI 0.72-1.40) or adverse events (RR 0.84, 95%CI 0.54-1.31) with tocilizumab or TNFi. A meta-analysis of three studies identified superior clinical response (RR 1.55, 95%CI 1.15-2.10) and adverse effect profile (RR 0.45, 95%CI 0.25-0.80) with tocilizumab than cyclophosphamide. Pooled data from uncontrolled studies identified clinical response in 85%(95%CI 79-91%) and angiographic stabilization in 82% (95%CI 68-94%). Our study suggests similar evidence for treating TAK with tocilizumab or TNFi, contrary to the ACR 2021 recommendations.
Topics: Humans; Tumor Necrosis Factor-alpha; Takayasu Arteritis; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Immunologic Factors
PubMed: 36652977
DOI: 10.1016/j.autrev.2023.103275 -
Seminars in Arthritis and Rheumatism Aug 2018To better communicate the results of randomized controlled trials (RCTs) of giant cell arteritis (GCA), we propose the use of the fragility index (FI), which is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To better communicate the results of randomized controlled trials (RCTs) of giant cell arteritis (GCA), we propose the use of the fragility index (FI), which is an intuitive measure defined as the minimum number of subjects whose status would have to change (e.g., from having the outcome to not) to render a statistically significant result nonsignificant, or vice-versa.
METHODS
We conducted a systematic review and random-effects meta-analysis of RCTs of glucocorticoid (GC) sparing strategies for relapse-free maintenance in GCA, and used the FI to simplify the presentation of results.
RESULTS
Ten RCTs (nine phase II and one phase III enrolling 645 subjects) were included. Tocilizumab, IV GC and methotrexate significantly improved the likelihood of being relapse free with relative risks and 95% confidence intervals of 3.54 (2.28, 5.51), 5.11 (1.39, 18.81) and 1.54 (1.02, 2.30); respectively. The median FI was 4.5 (range, 1-28), and was generally higher for negative RCTs (n = 6; median FI 4.5) than for positive RCTs (n = 4; median FI 3.5). The range of FI per treatment was (1-8) for methotrexate, (2-6) for anti-TNF agents, 4 for abatacept, 3 for IV GC pulses and (4-28) for tocilizumab.
CONCLUSION
Tocilizumab, IV GC and methotrexate improve the likelihood of being relapse-free in subjects with GCA. Assessment of GC sparing strategies in GCA has long depended on imprecise trials that would change significance if outcomes were reversed for a handful of subjects. FI may be used in rheumatology to simplify communication of statistical significance and overcome limitations of p-value.
Topics: Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Giant Cell Arteritis; Glucocorticoids; Humans; Immunosuppressive Agents; Methotrexate; Treatment Outcome
PubMed: 29496228
DOI: 10.1016/j.semarthrit.2017.12.009 -
The Cochrane Database of Systematic... Aug 2014Giant cell arteritis (GCA) is a common inflammatory condition that affects medium and large-sized arteries and can cause sudden, permanent blindness. At present there is... (Review)
Review
BACKGROUND
Giant cell arteritis (GCA) is a common inflammatory condition that affects medium and large-sized arteries and can cause sudden, permanent blindness. At present there is no alternative to early treatment with high-dose corticosteroids as the recommended standard management. Corticosteroid-induced side effects can develop and further disease-related ischaemic complications can still occur. Alternative and adjunctive therapies are sought. Aspirin has been shown to have effects on the immune-mediated inflammation in GCA, hence it may reduce damage caused in the arterial wall.
OBJECTIVES
To assess the safety and effectiveness of low-dose aspirin, as an adjunctive, in the treatment of giant cell arteritis (GCA).
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2013, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2014), EMBASE (January 1980 to January 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) web site (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 24 January 2014.
SELECTION CRITERIA
We planned to include only randomised controlled trials (RCTs) comparing outcomes of GCA with and without concurrent adjunctive use of low-dose aspirin.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the search results for trials identified by the electronic searches. No trials met our inclusion criteria, therefore we undertook no assessment of risk of bias or meta-analysis.
MAIN RESULTS
We found no RCTs that met the inclusion criteria.
AUTHORS' CONCLUSIONS
There is currently no evidence from RCTs to determine the safety and efficacy of low-dose aspirin as an adjunctive treatment in GCA. Clinicians who are considering the use of low-dose aspirin as an adjunctive treatment in GCA must also recognise the established haemorraghic risks associated with aspirin, especially in the context of concurrent treatment with corticosteroids. There is a clear need for effectiveness trials to guide the management of this life-threatening condition.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Chemotherapy, Adjuvant; Giant Cell Arteritis; Humans
PubMed: 25087045
DOI: 10.1002/14651858.CD010453.pub2 -
International Journal of Rheumatic... Aug 2016To investigate the association between giant cell arteritis (GCA) and risk of peripheral arterial disease (PAD). (Meta-Analysis)
Meta-Analysis Review
AIM
To investigate the association between giant cell arteritis (GCA) and risk of peripheral arterial disease (PAD).
METHODS
We conducted a systematic review and meta-analysis of observational cohort studies that reported relative risks, hazard ratios or standardized incidence ratios with 95% confidence comparing PAD risk in patients with GCA versus non-GCA subjects. Pooled risk ratios and 95% confidence intervals were calculated using a random-effect, generic inverse variance of DerSimonian and Laird.
RESULTS
Four studies with 9789 patients with GCA and 236 728 controls were identified and included in our data analysis. The pooled risk ratio of PAD among patients with GCA compared with controls was 1.88 (95% CI 1.04-3.41). The statistical heterogeneity was high with an I(2) of 89%.
CONCLUSION
Our study demonstrated a statistically significant increased risk of PAD among patients with GCA.
Topics: Case-Control Studies; Chi-Square Distribution; Giant Cell Arteritis; Humans; Observational Studies as Topic; Odds Ratio; Peripheral Arterial Disease; Risk Factors
PubMed: 26218931
DOI: 10.1111/1756-185X.12631 -
Rheumatology (Oxford, England) Nov 2021Takayasu arteritis (TAK) is a rare autoimmune rheumatic disease causing large-vessel vasculitis. Onset is typically between the ages of 20 and 30 years. It is associated... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Takayasu arteritis (TAK) is a rare autoimmune rheumatic disease causing large-vessel vasculitis. Onset is typically between the ages of 20 and 30 years. It is associated with substantial morbidity and mortality, notably due to its effects on the cardiovascular system. It has a poorly understood global epidemiology. Our objective was to systematically review the available evidence in order to calculate the incidence rate of TAK.
METHODS
Three databases (MEDLINE, PubMed and Embase) were searched in November 2019 and the results were screened by two reviewers. A random effects meta-analysis was then conducted in R to calculate the overall incidence rate. Heterogeneity was assessed using I2. The quality of the studies was assessed using an adapted Newcastle-Ottawa scale. Further subgroup analyses were performed by quality, sex, research setting and geographical location. Publication bias was assessed using a Begg's funnel plot.
RESULTS
The incidence rate for TAK was 1.11 per million person-years (95% CI 0.70-1.76). The heterogeneity in the data was extremely high in all analyses, which suggests that there was considerable variation in incidence rates across the different populations studied. TAK was found to be more common in women (incidence rate 2.01 per million person-years, 95% CI 1.39-2.90).
CONCLUSIONS
TAK is an extremely rare disease. It affects women more commonly than men. There is considerable variation in the incidence rate between populations. We suggest that future research should focus on discrete populations in order to better identify genetic and environmental risk factors.
Topics: Global Health; Humans; Incidence; Takayasu Arteritis
PubMed: 33944899
DOI: 10.1093/rheumatology/keab406 -
Joint Bone Spine Jan 2023The aim of this study was to estimate the timing of relapse, the prevalence of multiple relapses and the predictors of relapse in patients with giant cell arteritis... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The aim of this study was to estimate the timing of relapse, the prevalence of multiple relapses and the predictors of relapse in patients with giant cell arteritis (GCA).
METHODS
PubMed, Embase and Cochrane databases were searched from inception till November, 30 2021. Outcome measures include cumulative relapse rate (CRR) of first relapse at year 1, 2, and 5 after treatment initiation, CRR of second and third relapse and predictors of relapse.
RESULTS
Thirty studies (2595 patients) were included for timing of relapse, 16 studies (1947 patients) for prevalence of multiple relapses and 40 studies (4213 patients) for predictors of relapse. One-year, 2-year and 5-year CRRs were 32% [95% confidence interval (CI) 22-43%], 44% [95% CI 31-59%], and 47% [95% CI 27-67%], respectively. The duration of scheduled glucocorticoid therapy was negatively associated with the 1-year CRR (P=0.03). CRR of second and third relapse were 30% [95% CI 21-40] and 17% [95% CI 8-33%], respectively. Female sex (OR 1.43) and large vessel involvement (OR 2.04) were predictors of relapse.
CONCLUSION
Relapse occurred in almost half of GCA patients mainly during the first two years after diagnosis. One in three patients had multiple relapses. The optimal glucocorticoid tapering schedule, which seeks a balance between the lowest relapse risk and the shortest glucocorticoid duration, needs to be determined in future studies. Longer scheduled glucocorticoid therapy or early introduction of glucocorticoid-sparing agents may be warranted in female patients and patients with large vessel involvement.
Topics: Humans; Female; Glucocorticoids; Giant Cell Arteritis; Chronic Disease; Outcome Assessment, Health Care; Recurrence
PubMed: 36410684
DOI: 10.1016/j.jbspin.2022.105494 -
Autoimmunity Reviews Jul 2018Takayasu's Arteritis (TAK) affects mostly young women and causes significant morbidity. Most patients are refractory to glucocorticoids (GC) or relapse when GC doses are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Takayasu's Arteritis (TAK) affects mostly young women and causes significant morbidity. Most patients are refractory to glucocorticoids (GC) or relapse when GC doses are reduced. The objective of this study is to summarize the literature pertaining to the effectiveness of non-GC drugs for the treatment of TAK.
METHODS
MEDLINE and Embase were searched for English-language studies of TAK patients with a sample size >5. Studies were included if the effectiveness of non-GC drugs for the treatment of TAK was reported. Random effects meta-analyses of various effect measures were performed.
RESULTS
Of the 915 studies identified by the search, 14 of small molecule immunosuppressants (IS) and 25 of biologic therapies were included. Studies had a high risk of bias. Pooled remission rates were similar for both categories of non-GC drugs: 58% (95% CI: 40-74%) and 64% (95% CI: 56-72%), respectively. The relapse rate was 54% (95% CI: 39-68%) for IS therapies and 31% (95% CI: 22-41%) for biologics. Both significantly decreased GC doses and acute phase reactants. Observational studies suggested that anti-TNF agents were more effective than IS at maintaining remission. Randomized-controlled trials (RCTs) of biologics were of small sample size: abatacept was not effective and the trial of tocilizumab was underpowered to detect a difference in time to relapse versus placebo. Serious adverse events were uncommon.
CONCLUSIONS
Non-GC agents were moderately effective in inducing remission in TAK, but relapse rates were high. Larger, better designed studies are required to determine the optimal treatment regimen for TAK.
Topics: Abatacept; Antibodies, Monoclonal, Humanized; Biological Products; Glucocorticoids; Humans; Immunosuppressive Agents; Observational Studies as Topic; Remission Induction; Takayasu Arteritis; Tumor Necrosis Factor-alpha
PubMed: 29729444
DOI: 10.1016/j.autrev.2018.01.019 -
Rheumatology International Jul 2017The purpose of this study is to assess the effectiveness of mycophenolate mofetil (MMF) in treating Takayasu arteritis (TA) patients. Embase, Cochrane Library, Pubmed,... (Meta-Analysis)
Meta-Analysis Review
The purpose of this study is to assess the effectiveness of mycophenolate mofetil (MMF) in treating Takayasu arteritis (TA) patients. Embase, Cochrane Library, Pubmed, Clinicaltrials. Gov and three Chinese literature databases (VIP, CNKI, WanFang) were searched; randomized-controlled trials and observational studies that compared the efficacy before and after treatment with MMF were included. The efficacy outcomes were disease activity, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) values and steroid dosage. The results were expressed as mean differences with 95% confidence intervals. Compared with the baseline, there were significant reductions in the ESR (-14.92 [25.35, -4.48]), CRP values (-12.99 [-23.29, -2.68]) and the steroid dosage (-17.64 [-24.89, -10.4]) after the addition of MMF, and the disease tended to stabilize. Therefore, MMF might be an alternative immunosuppressive drug for TA for the control of disease activity and to taper the steroid dosage.
Topics: Adolescent; Adult; Biomarkers; Blood Sedimentation; C-Reactive Protein; Chi-Square Distribution; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Steroids; Takayasu Arteritis; Treatment Outcome; Young Adult
PubMed: 28364217
DOI: 10.1007/s00296-017-3704-7 -
Seminars in Arthritis and Rheumatism Oct 2022To conduct a systematic literature review and meta-analysis to estimate the proportion of fever of unknown origin (FUO) and inflammation of unknown origin (IUO) cases... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To conduct a systematic literature review and meta-analysis to estimate the proportion of fever of unknown origin (FUO) and inflammation of unknown origin (IUO) cases that are due to rheumatic disorders and the relative frequency of specific entities associated with FUO/IUO.
METHODS
We searched PubMed and EMBASE between January 1, 2002, and December 31, 2021, for studies with ≥50 patients reporting on causes of FUO/IUO. The primary outcome was the proportion of FUO/IUO patients with rheumatic disease. Secondary outcomes include the association between study and patient characteristics and the proportion of rheumatic disease in addition to the relative frequency of rheumatic disorders within this group. Proportion estimates were calculated using random-effects models.
RESULTS
The included studies represented 16884 patients with FUO/IUO. Rheumatic disease explained 22.2% (95%CI 19.6 - 25.0%) of cases. Adult-onset Still's disease (22.8% [95%CI 18.4-27.9%]), giant cell arteritis (11.4% [95%CI 8.0-16.3%]), and systemic lupus erythematosus (11.1% [95%CI 9.0-13.8%]) were the most frequent disorders. The proportion of rheumatic disorders was significantly higher in high-income countries (25.9% [95%CI 21.5 - 30.8%]) versus middle-income countries (19.5% [95%CI 16.7 - 22.7%]) and in prospective studies (27.0% [95%CI 21.9-32.8%]) versus retrospective studies (20.6% [95%CI 18.1-24.0%]). Multivariable meta-regression analysis demonstrated that rheumatic disease was associated with the fever duration (0.011 [95%CI 0.003-0.021]; P=0.01) and with the fraction of patients with IUO (1.05 [95%CI 0.41-1.68]; P=0.002).
CONCLUSION
Rheumatic disorders are a common cause of FUO/IUO. The care of patients with FUO/IUO should involve physicians who are familiar with the diagnostic workup of rheumatic disease.
Topics: Adult; Fever of Unknown Origin; Fluorodeoxyglucose F18; Humans; Inflammation; Prospective Studies; Retrospective Studies; Rheumatic Diseases
PubMed: 35868032
DOI: 10.1016/j.semarthrit.2022.152066