CanVasc consensus recommendations for the use of avacopan in antineutrophil cytoplasm antibody-associated vasculitis: 2022 addendum.

OBJECTIVE: In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence. METHODS: An updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation. RESULTS: Three new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering. CONCLUSION: These 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.

CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update.

OBJECTIVE: In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aims to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence. METHODS: A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014 to September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a 2-step modified Delphi procedure to reach > 80% consensus on the inclusion, wording, and grading of each new and revised recommendation. RESULTS: Eleven new and 16 revised recommendations were created and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary material for practical use was revised to reflect the updated recommendations. CONCLUSION: The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts.

Impending radiographic erosive progression over the following year in a cohort of consecutive patients with inflammatory polyarthritis: prediction by serum biomarkers.

BACKGROUND/PURPOSE: To evaluate biomarkers as predictors of impending erosion progression. METHODS: Variables were measured at baseline and annually up to 5 years in patients with recent-onset polyarthritis treated to zero swollen joints. Erosive status was defined as ≥5 Units in Sharp/van der Heijde Erosion Score; Rapid Erosive Progression (REP) was defined as an increase ≥5 Units in Erosion Scores between consecutive visits. Generalised estimating equations (GEEs) evaluated the effect on REP of positive anticyclic citrullinated peptides (ACPAs) and/or rheumatoid factor (RF), C-reactive protein ˃8.0 mg/L (High-CRP) and 14-3-3η protein ≥0.50 ng/mL (High-14-3-3η), alone and in combinations. RESULTS: Out of 2155 evaluations in 749 consecutive patients, REP occurred after 186 (8.6%) visits, including 13 (2.2%) in patients recruited since 2010. Only 18/537 (3.4%; 6/411 (1.5%) in non-erosive vs 12/126 (9.5%) in patients already erosive) visits without any positive biomarker were followed by REP; at least one biomarker was positive prior to REP in 168/186 (90.3%) visits. Being positive for all four biomarkers conferred a positive predictive value (PPV) of 30.0% (RR 21.8) in patients non-erosive at the visit versus 35.5% (RR 3.07) in those already erosive. High-14-3-3η increased REP only in visits with High-CRP (eg, RR 2.5 to 3.9 when ACPA also positive) and in patients with non-erosive status (eg, RR from 4.3 to 9.4 when also High-CRP). CONCLUSIONS: Adding High-14-3-3η to positive antibodies and CRP improves prediction of impending REP. Although REP is becoming rarer, signatures of biomarkers might help to adapt treatment strategies in at-risk individuals, even those already erosive.

Antineutrophil Cytoplasmic Antibodies Testing and Interpretation.

The discovery of antineutrophil cytoplasmic antibodies (ANCA) helped establish ANCA-associated vasculitis as a separate and well-defined clinical entity. Its progressive incorporation into the clinical diagnosis algorithms has made ANCA testing a cornerstone immunoassay embedded in the management of ANCA-associated vasculitis. After its description by indirect immunofluorescence, proteinase-3 and myeloperoxidase were identified as principal ANCA targets. ANCA, and proteinase-3 and myeloperoxidase immunoassessment, have undergone iterative rounds of improvement in sensitivity and specificity. This article traces landmarks in the development of ANCA tests, describes common pitfalls arising during ANCA interpretation, and discusses new technologies to improve the future of ANCA testing.

The first case of bacillus Calmette-Guérin-induced small-vessel central nervous system vasculitis.

To present an unrecognized vascular complication of bacillus Calmette-Guérin (BCG) therapy administered for superficial bladder carcinoma. We also review the potential mimickers for primary angiitis of the central nervous system (PACNS) as well as complications of intravesical BCG therapy. An 89-year-old Caucasian man with a history of relapsing high-grade bladder carcinoma treated with intravesical BCG presented with recurring episodes of right upper limb paresthesia with clumsiness and dysarthria. Magnetic resonance imaging of the head revealed multiple predominantly left-sided frontotemporal micronodular peri-vascular lesions. Left frontal lobe biopsy showed non-necrotizing granulomatous vasculitis. Ziehl staining was negative. Initially, he was treated for PACNS but his symptoms relapsed during every attempt to taper the corticosteroids. Six months later, he developed bilateral mycobacterial endophthalmitis, caused by Mycobacterium bovis. Brain biopsy was reviewed and confirmed the presence of perivascular mycobacteria. A retrospective diagnosis of BCG-induced central nervous system vasculitis was made and he was treated with high-dose corticosteroids, moxifloxacin, isoniazid, ethambutol, and rifampicin. BCG is a live attenuated form of Mycobacterium bovis widely used as tuberculosis vaccination and intravesical therapy for superficial forms of bladder cancer. Systemic complications affect roughly 5% of patients and can manifest months or years after the last instillation. Cases of endophthalmitis, meningitis, aortitis, or mycotic aneurysms have been described, but no reports of CNS vasculitis have been found. In disseminated forms of BCG infections, referred to as BCGitis, histopathology usually reveals granulomatous inflammation. Mycobacterial cultures are often negative, making this a diagnostic challenge. This is the first documented case of BCG-induced small-vessel CNS vasculitis. Mycobacterium bovis infection is rare and findings are often nonspecific, making the diagnosis very difficult. Other infectious and non-infectious causes must be ruled out appropriately before considering this entity.

Variations in the clinical practice of physicians managing Takayasu arteritis: a nationwide survey.

OBJECTIVE: Takayasu arteritis (TAK) is a large vessel vasculitis that predominately affects young women and can cause severe ischemic complications. Given the rarity of TAK, the management of this condition is challenging. We aim to describe current rheumatologist practices for the management of TAK and identify discrepancies and gaps in knowledge. METHODS: An online survey (developed by the Canadian Vasculitis Network and approved by the Canadian Rheumatology Association) containing 48 questions with regard to the diagnosis, monitoring and treatment of TAK was distributed to 495 Canadian adult and pediatric rheu-matologists by email. RESULTS: Sixty-six rheumatologists completed the survey (13% response rate): the majority (73%) were from academic centers and ≤25% reported managing more than ten patients in their career. For establishing the diagnosis of TAK, they relied on a combination of signs and symptoms of ischemia, elevations of inflammatory markers and vascular imaging (typically computed tomography and magnetic resonance angiography). The frequency of monitoring for disease activity and the methods employed (clinical, laboratory or imaging) were variable. All physicians used corticosteroids for the treatment of TAK, but 42% would treat for at least 6-12 months, 26% for 12-24 months and 23% would never stop corticosteroids. Fifty-three percent would always use an immunosuppressant (most commonly methotrexate or azathioprine) in addition to corticosteroids and the remainder would only start an immunosuppressant in patients with refractory or relapsing disease. CONCLUSION: Physician practices for the management of TAK are variable, suggesting that there are knowledge gaps, which may impact outcomes in patients with TAK.

Serum levels of 14-3-3η protein supplement C-reactive protein and rheumatoid arthritis-associated antibodies to predict clinical and radiographic outcomes in a prospective cohort of patients with recent-onset inflammatory polyarthritis.

BACKGROUND: Age, C-Reactive Protein (CRP) and autoantibodies (Abs) are associated with worse prognosis in patients with recent-onset inflammatory polyarthritis (EPA). Serum 14-3-3η protein is a joint-derived biomarker that up-regulates cytokines and enzymes that perpetuate local and systemic inflammation and may contribute to joint damage. Our objective was to evaluate, over a 5-year prospective period of observation, the additional prognostic potential of serum 14-3-3η protein in EPA patients. METHODS: Clinical variables, serum and radiographs (scored according to the Sharp/van der Heijde (SvH) method) were collected serially. Relationships between serum 14-3-3η protein and other biomarkers were computed with Spearman correlations. Outcomes were Simple Disease Activity Index (SDAI) scores and joint damage progression: ΔSvH for SvH score and ΔErosion for its Erosive component. The additional predictive contribution of 14-3-3η was defined using generalized estimating equations (GEE) and generalized linear mixed models (GLMM). RESULTS: Among 331 patients, baseline 14-3-3η was ≥0.19 and ≥0.50 ng/ml in 153 (46.2 %) and 119 (36.0 %), respectively; CRP was >8.0 mg/L in 207 (62.5 %), and at least one Ab (Rheumatoid Factor, anti-CCP2 or anti-Sa/citrullinated vimentin) was positive in 170 (51.5 %). Elevated 14-3-3η levels moderately correlated with positive Abs, but not with elevated CRP. Baseline 14-3-3η ≥0.19 ng/ml was associated with more radiographic progression over 5 years. The optimal levels of baseline 14-3-3η to predict radiographic progression was defined by ROC curves at 0.50 ng/ml. Levels of 14-3-3η ≥0.50 ng/ml at baseline were associated with lower likelihoods of ever reaching SDAI remission (RR 0.79 (95 % CI 0.64-0.98), p = 0.03) and higher subsequent progression of Total and Erosion SvH scores. Elevated levels of 14-3-3η during follow-up also predicted higher subsequent progression, even in patients in SDAI remission. Decreases of 14-3-3η levels by at least 0.76 ng/ml and reversion to negative during follow-up associated with less subsequent radiographic progression. In multivariate models, elevated 14-3-3η interacted with positive Abs, elevated CRP and older age to predict subsequent radiographic progression. CONCLUSIONS: Levels of 14-3-3η protein ≥0.50 ng/ml predict poorer clinical and radiographic outcomes in EPA, both at baseline and after initiation of treatment, even in SDAI remitters. 14-3-3η, CRP, age and Abs represent independent predictors of subsequent joint damage. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00512239 . Registered August 6, 2007.

CanVasc Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitides.

OBJECTIVE: The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties and researchers with expertise in vasculitis. One of its aims is to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. METHODS: Diagnostic and therapeutic questions were developed based on the results of a national needs assessment survey. A systematic review of existing non-Canadian recommendations and guidelines for the diagnosis and management of AAV and studies of AAV published after the 2009 European League Against Rheumatism/European Vasculitis Society recommendations (publication date: January 2009) until November 2014 was performed in the Medline database, Cochrane library, and main vasculitis conference proceedings. Quality of supporting evidence for each therapeutic recommendation was graded. The full working group as well as additional reviewers, including patients, reviewed the developed therapeutic recommendations and nontherapeutic statements using a modified 2-step Delphi technique and through discussion to reach consensus. RESULTS: Nineteen recommendations and 17 statements addressing general AAV diagnosis and management were developed, as well as appendices for practical use, for rheumatologists, nephrologists, respirologists, general internists, and all other healthcare professionals more occasionally involved in the management of patients with AAV in community and academic practice settings. CONCLUSION: These recommendations were developed based on a synthesis of existing international guidelines, other published supporting evidence, and expert consensus considering the Canadian healthcare context, with the intention of promoting best practices and improving healthcare delivery for patients with AAV.

CanVasc recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides - Executive summary.

The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties, including rheumatology and nephrology and researchers with expertise in vasculitis. One of its aims was to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides in Canada. This executive summary features the 19 recommendations and 17 statements addressing general AAV diagnosis and management, developed by CanVasc group based on a synthesis of existing international guidelines, other published supporting evidence and expert consensus considering the Canadian healthcare context.

Depressive symptoms predict future simple disease activity index scores and simple disease activity index remission in a prospective cohort of patients with early inflammatory polyarthritis.

OBJECTIVE: To determine whether depressive symptoms assessed in treated patients with early inflammatory polyarthritis (EPA) influence disease activity during follow-up. METHODS: Consecutively recruited EPA patients were actively treated to remission. Simple disease activity index (SDAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores were calculated at inclusion and up to 42 months into disease. SDAI scores were log-transformed to compute univariate and multivariate linear regressions. Parametric interval-censored Kaplan-Meier and survival regressions using Weibull distribution were used to assess time to and predictors of SDAI remission. RESULTS: A total of 275 EPA patients were recruited at a median of 4 months into disease. In multivariate linear regression models, accounting for baseline demographic, clinical, serological and functional variables and 12-month inflammation markers, CES-D scores at 12 months into disease were correlated (r(2) = 0.14) with subsequent SDAI scores. Patients with 12-month high CES-D (≥19; suggestive of depression) had a lower proportion of SDAI remission (31.3% vs 84.3%; P < 0.001) and reached SDAI remission less rapidly [hazard ratio = 0.25 (95% CI 0.12, 0.53); P < 0.001]. CONCLUSION: Each follow-up SDAI correlated significantly with 12-month depressive symptoms, a median of 7 months after initiation of treatment. CES-D scores suggestive of depression at 12 months were strongly correlated with delay and failure to reach remission later on. Depressive symptoms in treated EPA patients represent important clinical issues with long-term association with disease activity. Interventions to alleviate persistent depressive symptoms in treated EPA warrant careful evaluation of their potential to improve disease remission rates.

Development of Canadian Recommendations for the Management of ANCA-Associated Vasculitides: Results of the National Needs Assessment Questionnaire.

OBJECTIVES: To study variations in Canadian clinical practice patterns for the management of ANCA-associated vasculitis (AAV) and identify points to consider for the development of national recommendations. MATERIAL AND METHODOLOGY: A 30-item needs assessment questionnaire was sent to all members of the Canadian Vasculitis network (CanVasc), Canadian Rheumatology Association (CRA), Canadian Thoracic Society (CTS) and Canadian Society of Nephrology (CSN). Respondent characteristics, practice patterns, concerns and expectations were analyzed. RESULTS: Among 132 physicians who followed at least 1 vasculitis patient and responded to the survey, 39% stated that they felt confident in their management of AAV. Several variations in practice were observed regarding diagnostic procedure, induction and maintenance treatments and use of biologics; some were due to logistic constraints (difficulties in access to some specific tests, drugs or care; lack of health care coverage for the costs). The top 5 topics for which recommendations are expected involve treatment for remission induction, maintenance, refractory disease, and relapse as well as biologics. CONCLUSION: Practice variations identified in this needs assessment survey will serve to formulate key questions for the development of CanVasc recommendations.

Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels.

INTRODUCTION: We hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity. METHODS: Serum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort. The Wilcoxon rank-sum test, a t-test and Spearman's correlation analysis were utilized to determine relationships between variables. RESULTS: In both the Dartmouth and Sherbrooke cohorts, CXCL13 levels were selectively increased in seropositive relative to seronegative RA patients (P = 0.0002 and P < 0.0001 for the respective cohorts), with a strong correlation to both immunoglobulin M (IgM) and IgA RF levels (P < 0.0001). There was a weaker relationship to ACPA titers (P = 0.03 and P = 0.006, respectively) and total IgG (P = 0.02 and P = 0.14, respectively). No relationship was seen with regard to age, sex, shared epitope status or inclusion high-sensitivity C-reactive protein (hsCRP) in either cohort or regarding the presence of baseline erosions in the Sherbrooke Cohort, whereas a modest relationship with Disease Activity Score in 28 joints CRP (DAS28-CRP) was seen in the Dartmouth cohort but not the Sherbrooke cohort. CONCLUSION: Using both established and early RA cohorts, marked elevations of serum CXCL13 levels resided nearly completely within the seropositive population. CXCL13 levels exhibited a strong relationship with RF, whereas the association with clinical parameters (age, sex, DAS28-CRP and erosions) or other serologic markers (ACPA and IgG) was either much weaker or absent. Elevated serum CXCL13 levels may identify a subset of seropositive RA patients whose disease is shaped by or responsive to RF production.

Outcomes in recent-onset inflammatory polyarthritis differ according to initial titers, persistence over time, and specificity of the autoantibodies.

OBJECTIVE: To prospectively evaluate the predictive value of initial titers and subsequent variations of 3 rheumatoid arthritis­associated antibodies for outcomes at 30 months in patients with recent-onset polyarthritis. METHODS: IgM rheumatoid factor (RF), anti-Sa (citrullinated vimentin) antibodies, anti­ cyclic citrullinated peptide 2 (anti­CCP-2) antibodies, modified Health Assessment Questionnaire score, Disease Activity Score in 28 joints, and Sharp/van der Heijde radiologic scores were determined at baseline and at 18 and 30 months in a cohort of consecutive HLA­DR-typed treated patients with recent-onset polyarthritis aiming at remission. RESULTS: At inclusion, 113 (44.7%), 58 (22.9%), and 97 (38.3%) of 253 recent-onset polyarthritis patients were positive for RF, anti-Sa, and anti­CCP-2, respectively; at 30 months, 85 (33.6%), 31 (12.4%), and 100 (39.5%) patients were similarly positive. A low titer of any particular antibody was associated with higher risks for seroreversion. Similar to their persistent absence, reversion of RF and anti­CCP-2 was associated with low risks for severity. Patients who acquired RF or anti­CCP-2 after inclusion trended toward a poor prognosis. Relative to RF and anti­CCP-2 antibodies, only the presence of anti-Sa at inclusion, especially at higher titers and even when it subsequently disappeared, significantly predicted more rapid radiographic damage and lower remission rates at 30 months. CONCLUSION: In treated recent-onset polyarthritis, anti­CCP-2 prevalence is stable or increases slightly, whereas anti-Sa and RF frequently disappear. Subsequent reversion and conversion of RF and anti­CCP-2 blur the prognostic significance of initial RF and anti­CCP-2 positivity. Of the 3 antibodies, only anti-Sa, even if it disappears afterward, independently predicts severe outcomes.

The DERAA HLA-DR alleles in patients with early polyarthritis: protection against severe disease and lack of association with rheumatoid arthritis autoantibodies.

OBJECTIVE: To define the association of alleles encoding the HLA-DR rheumatoid arthritis (RA) protective epitope (DERAA) with the presence of RA-associated antibodies at study inclusion and with severe outcome in patients with early polyarthritis (EPA). METHODS: Consecutive EPA patients (n = 210) were evaluated early (mean of 4.8 months after diagnosis) and prospectively (for 30 months). HLA class II typing was performed by polymerase chain reaction using sequence-specific primers, and HLA-DR alleles DERAA, RA-associated shared epitope (SE), and non-SE/non-DERAA (neither SE nor DERAA) were identified. RA-associated antibodies identified were anti-Sa/citrullinated vimentin, anti-cyclic citrullinated peptide 2, and IgM rheumatoid factor. Severe disease was defined according to a preset threshold of joint destruction and/or functional limitation. RESULTS: DERAA and SE alleles were present in 62 and 110 of the 210 EPA patients, respectively. At 30 months, severe disease was present in 78 patients (37%). In contrast to SE alleles, DERAA alleles were not associated with the production of RA-associated antibodies, but were strongly protective against severe disease at 30 months (odds ratio 0.30, P < 0.001). DERAA alleles emerged as a strong, independent protective marker on multivariate analysis. The protective effect of DERAA was seen only in patients who did not already have erosions at study inclusion, was independent of the presence of antibodies, but was not associated with spontaneous remission. CONCLUSION: In our EPA cohort, the presence of a DERAA sequence was a strong independent predictor of a better prognosis, but only in the absence of erosive disease that was already present at inclusion. Identification of DERAA alleles may help in managing the large subgroup of EPA patients who do not have erosions at baseline.

Anti-Sa antibodies and antibodies against cyclic citrullinated peptide are not equivalent as predictors of severe outcomes in patients with recent-onset polyarthritis.

The prognostic value of two antibodies targeting citrullinated antigens, anti-Sa and anti-cyclic citrullinated peptide (CCP), present at inclusion, was evaluated prospectively in a cohort of 165 consecutive patients with recent-onset or early polyarthritis (EPA) followed for up to 30 months. Patients were treated according to current Good Clinical Practice standards. Predefined outcomes were severe arthritis and persistent arthritis. At inclusion, a median of 3 months after disease onset, 133 (81%) patients fulfilled at least four American College of Rheumatology criteria for rheumatoid arthritis and 30 (18%) had erosive changes on radiographs of hands and feet. Disease-modifying anti-rheumatic drugs were used in close to 80% of the patients at 30 months. Joint damage increased linearly over time, whereas disease activity declined markedly and remained low at each follow-up. Autoantibodies were identified in 76 (46%) patients: rheumatoid factor (RF) in 68 (41%), anti-CCP in 53 (33%), and anti-Sa in 46 (28%). All three antibodies were correlated, but anti-Sa antibodies best predicted severity at 18 and 30 months. RF and anti-CCP performed less well. For both outcomes, anti-Sa alone performed better than any combination of antibodies. The presence of any autoantibody identified about 50 to 60% of the patients with poor outcomes. In multivariate analysis, anti-Sa (odds ratio (OR) 8.83), the presence of erosions at inclusion (OR 3.47) and increasing age (OR 1.06/year) were significantly associated with severity, whereas RF and anti-CCP were not significant predictors. Persistent arthritis was present in up to 84% of patients; autoantibodies were specific but poorly sensitive predictors of this outcome. We conclude that assays for antibodies against citrullinated antigens differ in their ability to predict poorer outcomes in patients with EPA. In our EPA cohort treated in accordance with current standards, detection of anti-Sa but not of RF or anti-CCP antibodies, in combination with clinical and radiological variables present at the first encounter, allowed the identification of a subgroup of EPA patients suffering more rapid and more severe joint damage over 30 months.

Advances in the medical and surgical treatment of Takayasu arteritis.

PURPOSE OF REVIEW: Takayasu arteritis remains a therapeutic challenge. In spite of current treatments, progression of vascular lesions is observed frequently. The purpose of this article is to describe advances in therapeutic strategies for Takayasu arteritis. RECENT FINDINGS: Immunosuppressive agents including methotrexate, mycophenolate mofetil, and azathioprine added to corticosteroids can bring Takayasu arteritis into remission in many patients. Unfortunately, relapse is common when prednisone is tapered to dosages of 15 mg/day or less. A better understanding of pathogenesis has lead to trials with anti-tumor necrosis factor-alpha agents in patients with refractory disease. Preliminary results are encouraging. For patients who require revascularization intervention, both surgical and endovascular procedures can be performed that are safe, with low morbidity and mortality. The best long-term outcomes are achieved with conventional bypass grafts. Percutaneous transluminal angioplasty provides good results for short lesions. In contrast to the results in treating atherosclerosis, the use of conventional stents may not yield long-term vessel patency in Takayasu arteritis. Persistent inflammation and endothelial dysfunction may put patients with Takayasu arteritis at risk for premature atherosclerosis. SUMMARY: In the future, greater therapeutic success may be achieved by addressing both the inflammatory and the myointimal proliferative components of Takayasu arteritis. New drugs that target intimal hyperplasia, as well as drug-eluting stents, deserve to be studied for possible utility as adjuncts to present treatments.

Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis.

OBJECTIVE: Granulomatous inflammation is a typical feature of Takayasu arteritis (TA), and tumor necrosis factor (TNF) is important in the formation of granulomas. In this study, we assessed therapy with anti-TNF agents in patients with TA that was not controlled by glucocorticoid therapy or other immunosuppressants. METHODS: We conducted an open-label trial of anti-TNF therapy at 3 academic medical centers over a period of 4.25 years. Fifteen patients with active, relapsing TA (median 6 years) were selected. Seven received etanercept (later changed to infliximab in 3 patients), and 8 received infliximab. Relapses had occurred in all patients while they were receiving glucocorticoids and, in 13 patients, additional immunosuppressive drugs. No other agents were added to the treatment regimen concurrently with anti-TNF. If patients were receiving cytotoxic agents, the dosage was not increased. Clinical symptoms were recorded, and physical examinations, laboratory studies, and serial magnetic resonance imaging were performed. RESULTS: The median daily dose of prednisone required to maintain remission prior to anti-TNF therapy was 20 mg. Ten of the 15 patients achieved complete remission that was sustained for 1-3.3 years without glucocorticoid therapy. Four patients achieved partial remission, with a >50% reduction in the glucocorticoid requirement. At a median of 12 months of followup, the median dose of prednisone was 0. Therapy failed in 1 patient. In 9 of the 14 responders, an increase in the anti-TNF dosage was required to sustain remission. Two relapses occurred during periods when anti-TNF therapy (etanercept) was interrupted, but remission was reestablished upon reinstitution of therapy. CONCLUSION: In this pilot study of relapsing TA, addition of anti-TNF therapy resulted in improvement in 14 of 15 patients and sustained remission in 10 of 15 patients, who were able to discontinue glucocorticoid therapy. Anti-TNF may be a useful adjunct to glucocorticoids in the treatment of TA. Our results justify a randomized, controlled clinical trial of anti-TNF therapy for TA.

Takayasu's arteritis: vascular interventions and outcomes.

OBJECTIVE: To provide an analysis of outcomes of vascular interventions in 20 patients with Takayasu's arteritis (TA) who received care at the Cleveland Clinic Foundation between 1979 and 2001. METHODS: We performed a retrospective chart review. The primary outcome measure of our review was patency of vessels as assessed by repeat invasive angiography or magnetic resonance angiography. The secondary outcome measures included periprocedural complications, morbidity, and mortality. Interventions included bypass grafts, patch angioplasty, endarterectomy, percutaneous transluminal angioplasty (PTA), or stent placement. RESULTS: Sixty-two revascularization procedures were performed in 20 patients. Followup evaluations were available for 52 procedures. Eleven of 31 bypass grafts restenosed or occluded between one day to 168 months after surgery. Three of 7 PTA and 5 of 7 stents restenosed or became occluded after 1-72 months and 2-45 months of followup, respectively. There were no deaths associated with revascularization procedures. CONCLUSION: Despite providing short term benefit, endovascular revascularization procedures are associated with a high failure rate in patients with TA.