Recent advances in the treatment of giant cell arteritis.

Giant cell arteritis (GCA) is a systemic, granulomatous, large-vessel vasculitis that affects individuals over the age of 50 years. Morbidity from disease includes cranial manifestations which can cause irreversible blindness, while extra-cranial manifestations can cause vascular damage with large-artery stenosis, occlusions, aortitis, aneurysms, and dissections. Glucocorticoids while efficacious are associated with significant adverse effects. Furthermore, despite treatment with glucocorticoids, relapses are common. An understanding of the pathogenesis of GCA has led to the discovery of tocilizumab as an efficacious steroid-sparing therapy while additional therapeutic targets affecting different inflammatory pathways are under investigation. Surgical treatment may be indicated in cases of refractory ischemia or aortic complications but data on surgical outcomes are limited. Despite the recent advances, many unmet needs exist, including the identification of patients or subsets of GCA who would benefit from earlier initiation of adjunctive therapies, patients who may warrant long-term immunosuppression and medications that sustain permanent remission. The impact of medications like tocilizumab on long-term outcomes, including the development of aortic aneurysms and vascular damage also warrants investigation.

Vasculitis Mimics and Other Related Conditions.

The approach to diagnosis of primary systemic vasculitis can be challenging, often requiring consideration of important secondary causes of vasculitis and non-inflammatory mimics. An atypical pattern of vascular involvement and/or atypical features of primary vasculitis (eg, cytopenia, lymphadenopathy) should prompt a more thorough investigation into other diseases. Herein, we review selected mimics organized by the size of blood vessels typically affected.

Polyarteritis nodosa: an evolving primary systemic vasculitis.

Polyarteritis nodosa (PAN) is a primary form of vasculitis characterized by inflammation of primarily medium-sized arteries. Several key events have shaped the current spectrum of the disease including the separation of a subgroup with microscopic polyangiitis, the discovery of the association of hepatitis B, and the discovery of adenosine deaminase 2 deficiency (DADA2). With the discovery of secondary causes of PAN and changing nomenclature, the incidence of PAN has declined over time. Common manifestations include constitutional symptoms, skin involvement, peripheral neuropathy, gastrointestinal disease, and renal involvement. DADA2 is a genetic cause of medium vessel vasculitis that is important to distinguish from primary PAN as treatment with TNF inhibitors can prevent morbidity and mortality in those with a vasculitis phenotype. Treatment of systemic primary PAN involves the use of systemic immunosuppressive therapy largely guided by the severity of disease. With current treatment regimens, the prognosis has changed from a once uniformly fatal disease to a 5-year survival rate above 80%.

Self-Reported Data and Physician-Reported Data in Patients With Eosinophilic Granulomatosis With Polyangiitis: Comparative Analysis.

BACKGROUND: Patient-based registries can help advance research on rare diseases such as eosinophilic granulomatosis with polyangiitis (EGPA), a complex multiorgan form of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. OBJECTIVE: The aim of this study is to compare patient-reported and physician-reported data on manifestations, treatments, and outcomes for patients with EGPA. METHODS: We completed a comparative analysis of patients ≥18 years with EGPA in Canada and the United States from the following 2 cohorts: (1) The Vasculitis Patient-Powered Research Network (VPPRN), a self-enrolled secure portal with patient-entered data updated quarterly (2014-2019) and (2) the Vasculitis Clinical Research Consortium (VCRC) observational studies, a physician-entered database (2003-2019) of patients who fulfilled the 1990 American College of Rheumatology classification criteria for EGPA. The studied parameters included demographic characteristics, clinical manifestations, ANCA status, treatments, and relapses. RESULTS: Data from 195 patients with a validated diagnosis of EGPA in the VPPRN and 354 patients enrolled in the VCRC were analyzed. Compared to the VCRC cohort, the patients in the VPPRN cohort were more likely to be female (135/195, 69.2% compared to 209/354, 59%; P=.02) and younger at diagnosis (47.3 compared to 50.0 years; P=.03); both cohorts reported similar frequencies of asthma (177/184, 96.2% in the VPPRN cohort compared to 329/354, 92.9% in the VCRC cohort; P=.13) and cardiac manifestations (44/153, 28.8% compared to 75/354, 21.2%; P=.06), but the VPPRN cohort reported less frequent lung manifestations other than asthma and more frequent disease manifestations in all other organ systems. The ANCA positivity was 48.9% (64/131) in the VPPRN patients compared to 38.9% (123/316; P=.05) in the VCRC cohort. Relapsing disease after study enrollment was reported in 32.3% (63/195) of patients in the VPPRN compared to 35.7% (99/277) of patients in the VCRC. Most therapies (GC, cyclophosphamide, mepolizumab) were used at similar frequencies in both groups, except for rituximab with VPPRN patients reporting more use than the VCRC cohort (47/195, 24.1% compared to 29/277, 10.5%; P<.001). CONCLUSIONS: Overall, patients and physicians report manifestations of EGPA at similar frequencies. However, observed differences between patient and physician reports imply the potential occurrence of selection biases. These results support the use of patient-reported data in EGPA but also the need for careful consideration of disease-specific definitions for the study of EGPA and how patient- and physician-reported data are collected. TRIAL REGISTRATION: ClinicalTrials.gov NCT00315380, https://clinicaltrials.gov/ct2/show/NCT00315380; ClinicalTrials.gov NCT01241305, https://clinicaltrials.gov/ct2/show/NCT01241305.

Update on the Treatment of Giant Cell Arteritis and Polymyalgia Rheumatica.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are considered 2 diseases on the same spectrum due to their many underlying similarities. In recent years, both diseases have witnessed both diagnostic and treatment advances, which shaped the way we manage them. In this article, the authors focus on different diagnostic modalities in GCA as well as the presence of different clinical phenotypes and the role of screening for aortic involvement. The authors also discuss traditional treatments and the role of evolving steroid-sparing agents in the management of both GCA and PMR.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Kawasaki Disease.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of Kawasaki disease (KD), focusing on clinical scenarios more commonly addressed by rheumatologists. METHODS: Sixteen clinical questions regarding diagnostic testing, treatment, and management of KD were developed in the Patient/Population, Intervention, Comparison, and Outcomes (PICO) question format. Systematic literature reviews were conducted for each PICO question. We used the Grading of Recommendations, Assessment, Development and Evaluation method to assess the quality of evidence and formulate recommendations. Each recommendation required consensus from at least 70% of the Voting Panel. RESULTS: We present 1 good practice statement, 11 recommendations, and 1 ungraded position statement to guide the management of KD and clinical scenarios of suspected KD. These recommendations for KD are focused on situations in which input from rheumatologists may be requested by other managing specialists, such as in cases of treatment-refractory, severe, or complicated KD. The good practice statement affirms that all patients with KD should receive initial treatment with intravenous immunoglobulin (IVIG). In addition, we developed 7 strong and 4 conditional recommendations for the management of KD or suspected KD. Strong recommendations include prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in the setting of unexplained macrophage activation syndrome or shock. Conditional recommendations include use of IVIG with other adjuvant agents for patients with KD and high-risk features of IVIG resistance and/or coronary artery aneurysms. These recommendations endorse minimizing risk to the patient by using established therapy promptly at disease onset and identifying situations in which adjunctive therapy may be warranted. CONCLUSION: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and use of echocardiography in patients with suspected or confirmed KD.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Kawasaki Disease.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of Kawasaki disease (KD), focusing on clinical scenarios more commonly addressed by rheumatologists. METHODS: Sixteen clinical questions regarding diagnostic testing, treatment, and management of KD were developed in the Patient/Population, Intervention, Comparison, and Outcomes (PICO) question format. Systematic literature reviews were conducted for each PICO question. We used the Grading of Recommendations, Assessment, Development and Evaluation method to assess the quality of evidence and formulate recommendations. Each recommendation required consensus from at least 70% of the Voting Panel. RESULTS: We present 1 good practice statement, 11 recommendations, and 1 ungraded position statement to guide the management of KD and clinical scenarios of suspected KD. These recommendations for KD are focused on situations in which input from rheumatologists may be requested by other managing specialists, such as in cases of treatment-refractory, severe, or complicated KD. The good practice statement affirms that all patients with KD should receive initial treatment with intravenous immunoglobulin (IVIG). In addition, we developed 7 strong and 4 conditional recommendations for the management of KD or suspected KD. Strong recommendations include prompt treatment of incomplete KD, treatment with aspirin, and obtaining an echocardiogram in the setting of unexplained macrophage activation syndrome or shock. Conditional recommendations include use of IVIG with other adjuvant agents for patients with KD and high-risk features of IVIG resistance and/or coronary artery aneurysms. These recommendations endorse minimizing risk to the patient by using established therapy promptly at disease onset and identifying situations in which adjunctive therapy may be warranted. CONCLUSION: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and use of echocardiography in patients with suspected or confirmed KD.

Dose-dependent Pharmacological Response to Rituximab in the Treatment of Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

OBJECTIVE: Rituximab (RTX) is effective in the induction and maintenance of remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, uncertainty remains regarding the optimal maintenance dosing regimen. This work evaluates the relationship between variability in RTX dosing and pharmacological response in AAV. METHODS: A prospective cohort of patients with AAV (n = 28) with either granulomatosis with polyangiitis (n = 23) or microscopic polyangiitis (n = 5) receiving maintenance RTX therapy were followed in a single tertiary care academic medical center over a 2-year period. Patient demographics, RTX dosing information, and trough plasma RTX levels were collected along with laboratory measures of pharmacologic response, including B cell counts and ANCA titers. RESULTS: RTX dosing information from 94 infusions with 59 trough samples were collected with a mean ± SD dose of 640 ± 221 mg, dosing interval of 210 ± 88 days, and trough plasma RTX concentration of 622 ± 548 ng/mL. RTX trough concentrations were associated with RTX dose (ρ = 0.60, P < 0.0001) and dosing interval (ρ = -0.55, P < 0.0001). RTX dosing intensity (mg/d) was associated with RTX trough concentrations (ρ = 0.57, P < 0.0001). Higher dosing intensities were associated with undetectable B cell repopulation (P < 0.0001), but not negative ANCA titers (P = 0.60). Stratification of dosing intensities based on the standard dosing regimen of 500 mg every 6 months (2.4-3.3 mg/d) demonstrated that this regimen was associated with B cell repopulation in 8 of 17 doses (47%) compared to 0 of 23 doses (0%) with the high-dose regimen (> 3.3 mg/d; P < 0.0001). CONCLUSION: RTX maintenance dosing of 500 mg every 6 months may be inadequate to maintain B cell depletion in the treatment of AAV.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. METHODS: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. CONCLUSION: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low-quality evidence supporting the recommendations. CONCLUSION: This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Polyarteritis Nodosa.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). METHODS: Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. CONCLUSION: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) as exemplars of large vessel vasculitis. METHODS: Clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for GCA and TAK (27 for GCA, 27 for TAK). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of the evidence. Recommendations were developed by the Voting Panel, comprising adult and pediatric rheumatologists and patients. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 22 recommendations and 2 ungraded position statements for GCA, and 20 recommendations and 1 ungraded position statement for TAK. These recommendations and statements address clinical questions relating to the use of diagnostic testing, including imaging, treatments, and surgical interventions in GCA and TAK. Recommendations for GCA include support for the use of glucocorticoid-sparing immunosuppressive agents and the use of imaging to identify large vessel involvement. Recommendations for TAK include the use of nonglucocorticoid immunosuppressive agents with glucocorticoids as initial therapy. There were only 2 strong recommendations; the remaining recommendations were conditional due to the low quality of evidence available for most PICO questions. CONCLUSION: These recommendations provide guidance regarding the evaluation and management of patients with GCA and TAK, including diagnostic strategies, use of pharmacologic agents, and surgical interventions.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Polyarteritis Nodosa.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of systemic polyarteritis nodosa (PAN). METHODS: Twenty-one clinical questions regarding diagnostic testing, treatment, and management were developed in the population, intervention, comparator, and outcome (PICO) format for systemic, non-hepatitis B-related PAN. Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 16 recommendations and 1 ungraded position statement for PAN. Most recommendations were graded as conditional due to the paucity of evidence. These recommendations support early treatment of severe PAN with cyclophosphamide and glucocorticoids, limiting toxicity through minimizing long-term exposure to both treatments, and the use of imaging and tissue biopsy for disease diagnosis. These recommendations endorse minimizing risk to the patient by using established therapy at disease onset and identify new areas where adjunctive therapy may be warranted. CONCLUSION: These recommendations provide guidance regarding diagnostic strategies, use of pharmacologic agents, and imaging for patients with PAN.

2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVE: To provide evidence-based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel. RESULTS: We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low-quality evidence supporting the recommendations. CONCLUSION: This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases.

Kawasaki Disease: A Systematic Review and Meta-Analysis of Benefits and Harms of Common Treatments.

OBJECTIVE: Kawasaki disease (KD) is a self-limited vasculitis affecting medium-sized vessels with a predilection for the coronary arteries. Although treatment reduces the likelihood of developing of coronary artery aneurysms, 5% of patients still develop aneurysms despite treatment, making KD the leading cause of acquired heart disease in children in the United States. Consequently, there is a great deal of interest in optimizing treatment regimens, particularly for higher-risk patients, to decrease morbidity. The aim of this systematic review is to support the development of the American College of Rheumatology/Vasculitis Foundation for the diagnosis and management of KD, focusing on the more complex scenarios in which rheumatologists may become involved, such as high-risk and refractory disease. METHODS: Eighty-nine articles were considered for full review in this systematic literature review to address 16 Population, Intervention, Comparison, and Outcome questions related to KD. Data were abstracted in hierarchical fashion. Randomized control trials (RCTs) were considered first; if none were identified or if they contained insufficient information, comparative observational studies were then viewed, followed by single-arm observational studies/single arms from comparative studies. Only observational studies with more than 10 subjects with vasculitis were included. RESULTS: Eight RCTs and 28 observational studies that addressed the questions were identified. Two questions were addressed by RCTs, seven questions had at least some comparative observational studies, three questions were only addressed by single-arm data, and four questions had no relevant studies. CONCLUSION: This systematic review evaluates the benefits and harms of treatments for KD beyond first-line therapy.

Clinical Manifestations and Long-Term Outcomes of Eosinophilic Granulomatosis With Polyangiitis in North America.

OBJECTIVE: To describe clinical manifestations and outcomes in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in North America. METHODS: Analysis of patients aged 18 years or older who fulfilled the 1990 American College of Rheumatology Classification Criteria for EGPA enrolled in the Vasculitis Clinical Research Consortium from 2003 to 2019. Main clinical characteristics, treatments, outcomes, and accumulated damage were studied. RESULTS: The cohort included 354 patients; 59% female; age at diagnosis of 50.0 (±14) years; 39% were antineutrophil cytoplasm antibody (ANCA) positive. Time from diagnosis to last follow-up was 7.0 (±6.2) years; 49.4% had one or more relapse. Patients positive for ANCA more commonly had neurological and kidney involvement when compared with patients negative for ANCA, who had more cardiac and lung manifestations. At last study visit, only 35 (12.6%) patients had been off all therapy for more than 2 years during their follow-up. The overall mortality rate was 4.0% and did not differ by ANCA status or cyclophosphamide use. Scores on the Vasculitis Damage Index (VDI) for 134 patients with two or more visits and more than 1 year of follow-up increased from 1.7 (±1.8) at enrollment (3.7 [±5.1] years after diagnosis) to 3.35 (±2.1) at last follow-up (7.5 [±5.8] years after diagnosis), mainly represented by chronic asthma (67.5%), peripheral neuropathy (49.6%), and chronic sinusitis (31.3%). Longer duration of glucocorticoid use and relapse were associated with higher VDI scores. CONCLUSION: This analysis describes the many clinical manifestations and varied outcomes of EGPA and highlights the ongoing need to attain more sustained, long-term remission to limit the accrual of disease-related damage.

Giant Cell Arteritis: A Systematic Review and Meta-Analysis of Test Accuracy and Benefits and Harms of Common Treatments.

This systematic review compares treatment options for patients with giant cell arteritis (GCA) and evaluates the test accuracy of studies used in diagnosing and monitoring GCA. These studies were used to inform evidence-based recommendations for the American College of Rheumatology (ACR)/Vasculitis Foundation (VF) vasculitis management guidelines. A systematic review and search of articles in English in Ovid Medline, PubMed, Embase, and the Cochrane Library was conducted. Articles were screened for suitability, and studies presenting the highest level of evidence were given preference. Three hundred ninety-nine full-text articles addressing GCA questions were reviewed to inform 27 Population, Intervention, Comparison, and Outcome questions. No benefit was found with intravenous glucocorticoids (GCs) compared with high-dose oral GCs in patients with cranial ischemic symptoms (27.4% vs 12.3%; odds ratio [OR] 2.39 [95% confidence interval (CI) 0.75-7.62], [very low certainty of evidence]). Weekly tocilizumab with a 26-week GC taper was superior to a 52-week GC taper in patients achieving remission (risk ratio 4.00 [95% CI 1.97-8.12], [low certainty of evidence]). Non-GC immunosuppressive therapies with GCs compared with GCs alone showed no statistically significant in relapse at 1 year (OR 0.87 [95% CI 0.73-1.04], [moderate certainty of evidence]) or serious adverse events (OR 0.81 [95% CI 0.54-1.20]; [moderate certainty of evidence]). Temporal artery biopsy has a sensitivity of 61% (95% CI 38%-79%) and a specificity of 98% (95% CI 95%-99%) in patients with a clinical diagnosis of suspected GCA. This comprehensive systematic review synthesizes and evaluates the benefits and harms of different treatment options and the accuracy of commonly used tests for the diagnosis and monitoring of GCA.

Granulomatosis With Polyangiitis and Microscopic Polyangiitis: A Systematic Review and Meta-Analysis of Benefits and Harms of Common Treatments.

OBJECTIVE: The aim of this systemic review is to compare different treatments for patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) to inform evidence-based recommendations for the American College of Rheumatology (ACR)/Vasculitis Foundation (VF) Vasculitis Management Guidelines. METHODS: A systemic review was conducted by searching articles in English using OVID Medline, PubMed, Embase, and the Cochrane Library. Articles were screened for suitability in addressing PICO questions, with studies presenting the highest level of evidence given preference. RESULTS: A total of 729 full-text articles addressing GPA and MPA PICO questions were reviewed. For remission induction, rituximab was shown to be noninferior to cyclophosphamide (CYC) (odds ratio [OR]: 1.55, moderate certainty of evidence). The addition of plasma exchange to induction therapy in severe disease did not improve the composite end point of death or end stage renal disease (hazard ratio [HR]: 0.86 [95% confidence interval CI: 0.65, 1.13], moderate certainty of evidence). In nonsevere disease, methotrexate was noninferior to CYC for induction of remission (remission at 6 months of 90% vs. 94%). For maintenance of remission, methotrexate and azathioprine showed no difference in the risk of relapse over a mean follow-up of 29 months (HR: 0.92, [95% CI: 0.52, 1.65]low certainty of evidence). As maintenance therapy, rituximab was superior to a tapering azathioprine strategy in major relapse-free survival at 28 months (HR: 6.61, [95% CI: 1.56, 27.96], moderate certainty of evidence). In two randomized trials, longer-term azathioprine maintenance therapy (>24 months) is associated with fewer relapses without an increase in adverse events. CONCLUSION: This comprehensive systematic review synthesizes and evaluates the benefits and toxicities of different treatment options for GPA and MPA.

Update on the Treatment of Giant Cell Arteritis and Polymyalgia Rheumatica.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are considered 2 diseases on the same spectrum due to their many underlying similarities. In recent years, both diseases have witnessed both diagnostic and treatment advances, which shaped the way we manage them. In this article, the authors focus on different diagnostic modalities in GCA as well as the presence of different clinical phenotypes and the role of screening for aortic involvement. The authors also discuss traditional treatments and the role of evolving steroid-sparing agents in the management of both GCA and PMR.

Polyarteritis Nodosa: A Systematic Review of Test Accuracy and Benefits and Harms of Common Treatments.

OBJECTIVE: The object of this study was to analyze the benefits and harms of different treatment options and to analyze test accuracy used in the evaluation of patients with primary systemic polyarteritis nodosa (PAN). METHODS: A systematic search of published English-language literature was performed in Ovid Medline, PubMed, Embase, and the Cochrane Library from the inception of each database through August 2019. Articles were screened for suitability in addressing patient, intervention, comparison, and outcome questions, with studies presenting the highest level of evidence given preference. RESULTS: Of 137 articles selected for data abstraction, we analyzed 21 observational studies and seven randomized controlled trials (RCTs). The results showed indirect evidence that a deep skin biopsy provides good diagnostic accuracy. A combined nerve and muscle biopsy should be obtained for patients with PAN with peripheral neuropathy. Cyclophosphamide with high-dose glucocorticoids (GCs) is effective as an induction treatment for newly diagnosed active and severe PAN. GC monotherapy is adequate in the majority of patients with nonsevere PAN, although it has a high relapse rate with GC taper. There was insufficient data in determining the optimal duration of non-GC and GC maintenance therapy. Tumor necrosis factor inhibitors are effective treatment for patients with deficiency of adenosine deaminase 2 (DADA2) with stroke and vasculitis manifestations. CONCLUSION: This comprehensive systematic review synthesizes and evaluates the harms and benefits of different treatment options and the accuracy of commonly used tests for the diagnosis of systemic PAN. Data for diagnosis and management of PAN and DADA2 are mostly limited to observational studies. More high-quality RCTs are needed.