Glucocorticoid-sparing Agents Research Articles

Myositis-associated interstitial lung disease

Introduction/ObjectiveTo review the epidemiology, general clinical aspects and diagnosis, impact on morbidity and mortality, and general treatment approaches for myositis-associated ILD. Materials and methodsThe relevant literature was reviewed. ResultsThe clinical, radiographic, and histopathological features of interstitial lung disease (ILD) in idiopathic inflammatory myopathies (IIM) are similar to idiopathic ILD. Patients with a known diagnosis of myositis require prompt clinical evaluation including the determination of myositis-associated autoantibodies. Patients possessing autoantibodies associated with ILD or those with any pulmonary symptoms should undergo a pulmonary function test and high-resolution CT (HRCT) scanning of their lungs. ConclusionDespite the lack of placebo-controlled trials, systemic glucocorticoids are considered the mainstay of initial treatment of myositis-associated ILD. Glucocorticoid-sparing agents are often concomitantly administered, particularly in patients with severe disease. The first-line conventional immunosuppressive drugs include either mycophenolate mofetil or azathioprine. If these agents fail or if the pulmonary features are severe or rapidly progressive, then more aggressive immunosuppressive or immunomodulatory therapy including cyclophosphamide, tacrolimus or cyclosporine, rituximab, IVIg, or tofacitinib can be considered. Further investigations are required to assess the role of novel therapies in the treatment of myositis-associated ILD.

Current and future advances in practice: IgG4-related disease.

IgG4-related disease (IgG4-RD) is an increasingly recognized cause of fibroinflammatory lesions in patients of diverse racial and ethnic backgrounds and is associated with an increased risk of death. The aetiology of IgG4-RD is incompletely understood, but evidence to date suggests that B and T cells are important players in pathogenesis, both of which are key targets of ongoing drug development programmes. The diagnosis of IgG4-RD requires clinicopathological correlation because there is no highly specific or sensitive test. Glucocorticoids are highly effective, but their use is limited by toxicity, highlighting the need for studies investigating the efficacy of glucocorticoid-sparing agents. B cell-targeted therapies, particularly rituximab, have demonstrated benefit, but no randomized clinical trials have evaluated their efficacy. If untreated or under-treated, IgG4-RD can cause irreversible organ damage, hence close monitoring and consideration for long-term immunosuppression is warranted in certain cases.

The IL-17 pathway as a target in giant cell arteritis.

The network of IL-17 cytokines is considered a key component of autoimmune and inflammatory processes. Blocking IL-17 showed great success in psoriasis as well as psoriatic arthritis, and in patients with axial spondyloarthritis. Secukinumab is one of the approved IL-17A inhibitors for these diseases and is now routinely used. In giant cell arteritis, a large vessel vasculitis, there is accumulating evidence for a pathogenic role of IL-17 and Th17 cells, which are part of the CD4+ T-cell subset. Giant cell arteritis occurs in individuals over 50 years of age and many have relative contraindications to glucocorticoid therapy, which today still represents the mainstay therapy. Despite the approval of tocilizumab, which targets the IL-6 receptor, a high demand for glucocorticoid-sparing agents remains that combine the effective suppression of the acute inflammation observed in giant cell arteritis with a safety profile that matches the needs of an older patient population. The first results from a phase II proof-of-principle study (TitAIN) support an optimistic outlook on a potential new treatment option with secukinumab in giant cell arteritis.

Myositis-associated interstitial lung disease

Introduction/ObjectiveTo review the epidemiology, general clinical aspects and diagnosis, impact on morbidity and mortality, and general treatment approaches for myositis-associated ILD. Materials and methodsThe relevant literature was reviewed. ResultsThe clinical, radiographic, and histopathological features of interstitial lung disease (ILD) in idiopathic inflammatory myopathies (IIM) are similar to idiopathic ILD. Patients with a known diagnosis of myositis require prompt clinical evaluation including the determination of myositis-associated autoantibodies. Patients possessing autoantibodies associated with ILD or those with any pulmonary symptoms should undergo a pulmonary function test and high-resolution CT (HRCT) scanning of their lungs. ConclusionDespite the lack of placebo-controlled trials, systemic glucocorticoids are considered the mainstay of initial treatment of myositis-associated ILD. Glucocorticoid-sparing agents are often concomitantly administered, particularly in patients with severe disease. The first-line conventional immunosuppressive drugs include either mycophenolate mofetil or azathioprine. If these agents fail or if the pulmonary features are severe or rapidly progressive, then more aggressive immunosuppressive or immunomodulatory therapy including cyclophosphamide, tacrolimus or cyclosporine, rituximab, IVIg, or tofacitinib can be considered. Further investigations are required to assess the role of novel therapies in the treatment of myositis-associated ILD.

Pulmonary sarcoidosis: A comprehensive review: Past to present

Sarcoidosis is a sterile non-necrotizing granulomatous disease without known causes that can involve multiple organs with a predilection for the lung and thoracic lymph nodes. Worldwide it is estimated to affect 2–160/100,000 people and has a mortality rate over 5 years of approximately 7%. For sarcoidosis patients, the cause of death is due to sarcoid in 60% of the cases, of which up to 80% are from advanced cardiopulmonary failure (pulmonary hypertension and respiratory microbial infections) in all races except in Japan were greater than 70% of the sarcoidosis deaths are due to cardiac sarcoidosis.Scadding stages for pulmonary sarcoidosis associates with clinical outcomes. Stages I and II have radiographic remission in approximately 30%–80% of cases. Stage III only has a 10%–40% chance of resolution, while stage IV has no change of resolution. Up to 40% of pulmonary sarcoidosis patients progress to stage IV disease with lung parenchyma fibroplasia, bronchiectasis with hilar retraction and fibrocystic disease. These patients are at highest risk for the development of precapillary pulmonary hypertension, which may occur in up to 70% of these patients. Sarcoid patients with pre-capillary pulmonary hypertension can respond to targeted pulmonary arterial hypertension medications. Stage IV fibrocytic sarcoidosis with significant pulmonary physiologic impairment, >20% fibrosis on HRCT or pre-capillary pulmonary hypertension have the highest risk of mortality, which can be >40% at 5-years.First line treatment for patients who are symptomatic (cough and dyspnea) with parenchymal infiltrates and abnormal pulmonary function testing (PFT) is oral glucocorticoids, such as prednisone with a typical starting dose of 20–40 mg daily for 2 weeks to 2 months. Prednisone can be tapered over 6–18 months if symptoms, spirometry, PFTs, and radiographs improve. Prolonged prednisone may be required to stabilize disease. Patients requiring prolonged prednisone ≥10 mg/day or those with adverse effects due to glucocorticoids may be prescribed second and third line treatements. Second and third line treatments include immunosuppressive agents (e.g., methotrexate and azathioprine) and anti-tumor necrosis factor (TNF) medication; respectively. Effective treatments for advanced fibrocystic pulmonary disease are being explored. Despite different treatments, relapse rates range from 13% to 75% depending on the stage of sarcoid, number of organs involved, socioeconomic status, and geography. ConclusionThe mortality rate for sarcoidosis over a 5 year follow up is approximately 7%. Unfortunately, 10%–40% of patients with sarcoidosis develop progressive pulmonary disease, and >60% of deaths resulting from sarcoidosis are due to advance cardiopulmonary disease. Oral glucocorticoids are the first line treatment, while methotrexate and azathioprine are considered second and anti-TNF agents are third line treatments that are used solely or as glucocorticoid sparing agents for symptomatic extrapulmonary or pulmonary sarcoidosis with infiltrates on chest radiographs and abnormal PFT. Relapse rates have ranged from 13% to 75% depending on the population studied.

Epidemiology and predictors of relapse in giant cell arteritis: A systematic review and meta-analysis.

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). 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. 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. 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.

Clinical Images: Dacryoadenitis in eosinophilic granulomatosis with polyangiitis mimicking immunoglobulin G4-related disease.

The patient, a 26-year-old woman, presented with a 2-week history of acute swelling in both lacrimal glands (A). She had recently developed uncontrolled asthma and nasal polyps. The laboratory test results were notable for an absolute eosinophil count of 5300 cells per μl (reference range 100-400 μl), exceeding 50% of circulating leukocytes. The antineutrophil cytoplasmic antibody test result was negative. Magnetic resonance imaging of the head confirmed swelling of the bilateral lacrimal glands (B, yellow arrowheads) and rhinosinusitis. A biopsy of her lacrimal gland revealed eosinophil-rich necrotizing granulomatous inflammation with vasculitis (C). Her serum immunoglobulin G4 (IgG4) level was slightly elevated (265 mg/dl, normal upper limit is 121 mg/dl), but IgG4 immunostaining of the biopsy specimen did not show a significant finding. A diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) was made. Treatment with 30 mg of prednisone was initiated, which was gradually tapered without glucocorticoid-sparing agents over 12 months. The swelling of her lacrimal glands resolved, and she was free of symptoms, including asthma and lacrimal gland swelling, at the 12-month follow-up. In summary, EGPA can present with lacrimal gland swelling and mimic IgG4-related Mikulicz disease (1, 2). A histopathological examination of the swollen lacrimal gland is the key to differentiating EGPA from IgG4-related Mikulicz disease in such cases. Disclosureform Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Indirect Comparison of Glucocorticoid-Sparing Agents for Remission Maintenance in Giant Cell Arteritis: A Network Meta-analysis

ObjectiveTo compare and rank the effect of glucocorticoid-sparing agents in giant cell arteritis (GCA), for which several drugs have been evaluated but with a benefit-risk balance that remains uncertain. MethodsThe MEDLINE and Clinical Trials databases were searched up to November 2021; all randomized controlled trials investigating glucocorticoids in GCA were included. The glucocorticoid regimen was dichotomized into short (≤6 months) or prolonged (>6 months) use. Risk of relapse and safety were estimated using network meta-analysis with frequentist random effects models. ResultsOf the 96 records screened, 8 trials were included (572 patients). The trials compared glucocorticoids and a sparing agent: tocilizumab (2 trials), oral methotrexate (3 trials), infliximab (1 trial), etanercept (1 trial), and adalimumab (1 trial). The pooled prevalence of GCA relapse was 52.6% (95% CI, 38.1 to 66.9). The risk of relapse was significantly lower with tocilizumab compared with methotrexate (relative risk [RR], 0.41; 95% CI, 0.17 to 0.97) and prolonged (RR, 0.41; 95% CI, 0.20 to 0.83) and short (RR, 0.32; 95% CI, 0.16 to 0.66) glucocorticoid use. The risk of relapse was not significantly different with methotrexate compared with short (RR, 0.79; 95% CI, 0.48 to 1.31) and prolonged (RR, 0.95; 95% CI, 0.31 to 2.89) glucocorticoid use. The frequency of serious adverse events and serious infection was comparable between the different drugs. The certainty of the evidence was low to very low. ConclusionThis meta-analysis suggests that tocilizumab may be superior to other sparing agents to prevent GCA relapse, but with a low to very low certainty of evidence, and that safety is comparable to the other drugs. RegistrationThe protocol of the meta-analysis is registered in the international prospective register of systematic reviews PROSPERO (https://www.crd.york.ac.uk/prospero/; registration CRD42020112387).

Comparing treatment options for large vessel vasculitis

ABSTRACT Introduction Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the major forms of large vessel vasculitis (LVV). Glucocorticoids represent the cornerstone of LVV treatment, however, relapses and recurrences frequently occur when they are tapered or stopped, determining a prolonged exposure to glucocorticoids and a subsequent increased risk of glucocorticoid-related side effects. Therefore, conventional and biologic immunosuppressive drugs have been proposed to obtain a glucocorticoid-sparing effect. Areas covered We searched PubMed® using the keywords ‘giant cell arteritis/drug therapy’ and ‘Takayasu Arteritis/drug therapy’ OR ‘Takayasu Arteritis/surgery’ This review focuses on the management of LVV, based on the current evidence while highlighting the differences in terms of therapeutic management of TAK and GCA. Expert opinion Conventional disease modifying anti-rheumatic drugs, such as methotrexate or azathioprine, are recommended in association to glucocorticoids for selected GCA and all TAK patients. Two randomized placebo-controlled trials recently demonstrated the efficacy of tocilizumab in reducing relapses and cumulative prednisone dosage in GCA patients with newly diagnosed or relapsing disease. Observational evidence and two small randomized controlled trials support the use of TNF-alpha inhibitors and tocilizumab as glucocorticoid-sparing agents in relapsing TAK, albeit high-quality evidence regarding the management of TAK is still lacking.

An update on polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease affecting people older than 50 years and is 2-3 times more common in women. The most common symptoms are pain and morning stiffness in the shoulder and pelvic girdle and the onset may be acute or develop over a few days to weeks. General symptoms such as fatigue, fever and weight loss may occur, likely driven by systemic IL-6 signalling. The pathology includes synovial and periarticular inflammation and muscular vasculopathy. A new observation is that PMR may appear as a side effect of cancer treatment with checkpoint inhibitors. The diagnosis of PMR relies mainly on symptoms and signs combined with laboratory markers of inflammation. Imaging modalities including ultrasound, magnetic resonance imaging and positron emission tomography with computed tomography are promising new tools in the investigation of suspected PMR. However, they are still limited by availability, high cost and unclear performance in the diagnostic workup. Glucocorticoid (GC) therapy is effective in PMR, with most patients responding promptly to 15-25mg prednisolone per day. There are challenges in the management of patients with PMR as relapses do occur and patients with PMR may need to stay on GC for extended periods. This is associated with high rates of GC-related comorbidities, such as diabetes and osteoporosis, and there are limited data on the use of disease-modifying antirheumatic drugs and biologics as GC sparing agents. Finally, PMR is associated with giant cell arteritis that may complicate the disease course and require more intense and prolonged treatment.

OP0182 SECUKINUMAB IN GIANT CELL ARTERITIS: THE RANDOMISED, PARALLEL-GROUP, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTRE PHASE 2 TitAIN TRIAL

BackgroundLittle is known about glucocorticoid-sparing agents in giant cell arteritis (GCA) except for IL-6 inhibition. Secukinumab (SEC) has shown significant improvements in the signs and symptoms of IL-17A driven medical conditions such as plaque psoriasis, psoriatic arthritis, and axial spondyloarthritis.1,2 It has a favourable long-term safety profile.1,2ObjectivesTitAIN is the first randomised controlled trial investigating the potential efficacy, safety, and tolerability of SEC in GCA patients (pts).MethodsThis phase 2, randomised, double-blind, placebo (PBO) controlled, multicentre, proof-of-concept trial enrolled pts (aged ≥50 years) with new onset (diagnosed within 6 weeks (wks) of baseline) or relapsing (diagnosed >6 wks from baseline) GCA, naïve to biological therapy. Pts were randomised (1:1) to SEC 300 mg or PBO initially administered wkly (5 doses) and every 4 wks thereafter through Wk 48 (last dose), in combination with a 26-wk prednisolone taper regimen starting from baseline. Proportion of GCA pts in sustained remission until Wk 28 was the primary endpoint assessed by a Bayesian analysis of the posterior distribution with non-responder imputation. Other key endpoints included proportion of GCA pts in sustained remission until Wk 52 (based on study data with non-responder imputation) and time to first GCA flare after baseline.ResultsOut of 52 randomised pts (SEC, n=27; PBO, n=25), 71.2% (n=37) completed study treatment (SEC, 81.5%; PBO, 60.0%). Overall, 42 (80.8%) pts had new onset GCA and 10 (19.2%) pts had relapsing GCA at baseline. Proportion (posterior median with 95% credibility interval) of GCA pts in sustained remission until Wk 28 was higher with SEC, 70.1% (51.6%-84.9%), than with PBO, 20.3% (12.4%-30.0%); odds ratio (posterior median with 95% credibility interval), 9.31 (3.54-26.29) (Table 1). Until Wk 52, proportion (95% confidence interval) of GCA pts in sustained remission were 59.3% (38.8%-77.6%) in SEC group and 8.0% (1.0%-26.0%) in PBO group (Table 1). Median (95% confidence interval) time to first GCA flare after baseline was not reached for GCA pts treated with SEC and was 197.0 (101.0-280.0) days for PBO (Figure 1). Overall, treatment-emergent adverse events (AEs) occurred in 98.1% (SEC vs PBO, 100.0% vs 96.0%) and serious AEs in 32.7% (SEC vs PBO, 22.2% vs 44.0%) pts. Two pts in each SEC and PBO groups had AEs that led to study drug discontinuation and 1 pt in each group had AEs that led to death (not treatment-related). There were no new or unexpected safety signals identified with SEC treatment.Table 1.Proportion of GCA patients with sustained remission (Full analysis set) until Week 28 and 52Proportion of ptsSecukinumab (N=27)Placebo (N=25)Median percentage (95% credibility interval), Wk 2870.1% (51.6%, 84.9%)20.3% (12.4%, 30.0%)Percentage (95% confidence interval), Wk 5259.3% (38.8%, 77.6%)8.0% (1.0%, 26.0%)The full analysis set comprises all pts to whom study treatment has been assigned by randomisation and who received at least one dose of randomised study treatment (secukinumab or placebo).GCA, giant cell arteritis; N, number of pts in each treatment group in the full analysis set, pts, patients; Wk, WeekFigure 1.Kaplan-Meier plot of time to first GCA flare from baseline up to Week 52 (Full analysis set)ConclusionSEC demonstrated a higher sustained remission rate and longer time to first GCA flare vs PBO through 52 wks in pts with GCA. This proof-of-concept phase 2 study supports further development of SEC as a potential treatment in combination with 26 wk glucocorticoid taper for pts with GCA.

Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial

BackgroundPolymyalgia rheumatica is the second most common inflammatory rheumatic disease of people >50 years. Glucocorticoid therapy is highly effective, but many patients require treatment for several years. Effective glucocorticoid sparing...

Efficacy of rituximab in patients with polymyalgia rheumatica: a double-blind, randomised, placebo-controlled, proof-of-concept trial

Background Glucocorticoids remain the cornerstone of polymyalgia rheumatica treatment, but their use has several drawbacks, such as long treatment duration and glucocorticoid-related adverse events. Effective glucocorticoid-sparing agents with a strong evidence base in polymyalgia rheumatica are absent. As B cells have been implicated in the pathogenesis of polymyalgia rheumatica, we aimed to evaluate the efficacy of rituximab for the treatment of polymyalgia rheumatica. Methods We did a double-blind, randomised, placebo-controlled, proof-of-concept trial at Sint Maartenskliniek, Nijmegen, Netherlands. We enrolled patients with polymyalgia rheumatica according to the 2012 European League Against Rheumatism and American College of Rheumatology criteria, who were recently diagnosed or who had relapsed on prednisolone and were unable to taper their dose to less than 7·5 mg per day. Participants were randomly assigned (1:1) to a single intravenous infusion of rituximab 1000 mg or placebo, with a 17-week glucocorticoid tapering scheme. Participants and care and research personnel were masked to treatment assignment and randomisation sequence. The primary outcome was glucocorticoid-free remission at 21 weeks after infusion in patients who completed the study. This trial is registered with EudraCT (2018-002641-11) and the Dutch trial database (NL7414). Findings Between Jan 14, 2019, and March 10, 2020, 116 patients were screened and 49 (42%) were enrolled. 47 patients (38 who were recently diagnosed, nine who had relapsed on prednisolone) completed the study: 23 (49%) in the rituximab group and 24 (51%) in the placebo group. Mean age (SD) in years was 64 (8) in the rituximab group and 66 (10) in the placebo group, the proportion of women was 11 (48%) of 23 versus 13 (54%) of 24, and all participants were White. 11 (48%) of 23 patients in the rituximab group and five (21%) of 24 in the placebo group achieved glucocorticoid-free remission at 21 weeks (difference 27% [one-sided 95% CI 4]; relative risk 2·3 [1·1]; p=0·049). Ten infusion-related complaints occurred in the rituximab group versus three in the placebo group (relative rate 3·5 [one-sided 95% CI 1·3]). One serious adverse event occurred (pulmonary embolism; in the rituximab group), and there were no deaths. Interpretation Rituximab was shown to be efficacious in combination with 17-week glucocorticoid treatment compared with glucocorticoid treatment alone in terms of glucocorticoid-free remission in patients with polymyalgia rheumatica. If these findings are confirmed by larger trials, rituximab could be a valuable glucocorticoid-sparing treatment for patients with polymyalgia rheumatica. Funding Sint Maartenskliniek. Glucocorticoids remain the cornerstone of polymyalgia rheumatica treatment, but their use has several drawbacks, such as long treatment duration and glucocorticoid-related adverse events. Effective glucocorticoid-sparing agents with a strong evidence base in polymyalgia rheumatica are absent. As B cells have been implicated in the pathogenesis of polymyalgia rheumatica, we aimed to evaluate the efficacy of rituximab for the treatment of polymyalgia rheumatica. We did a double-blind, randomised, placebo-controlled, proof-of-concept trial at Sint Maartenskliniek, Nijmegen, Netherlands. We enrolled patients with polymyalgia rheumatica according to the 2012 European League Against Rheumatism and American College of Rheumatology criteria, who were recently diagnosed or who had relapsed on prednisolone and were unable to taper their dose to less than 7·5 mg per day. Participants were randomly assigned (1:1) to a single intravenous infusion of rituximab 1000 mg or placebo, with a 17-week glucocorticoid tapering scheme. Participants and care and research personnel were masked to treatment assignment and randomisation sequence. The primary outcome was glucocorticoid-free remission at 21 weeks after infusion in patients who completed the study. This trial is registered with EudraCT (2018-002641-11) and the Dutch trial database (NL7414). Between Jan 14, 2019, and March 10, 2020, 116 patients were screened and 49 (42%) were enrolled. 47 patients (38 who were recently diagnosed, nine who had relapsed on prednisolone) completed the study: 23 (49%) in the rituximab group and 24 (51%) in the placebo group. Mean age (SD) in years was 64 (8) in the rituximab group and 66 (10) in the placebo group, the proportion of women was 11 (48%) of 23 versus 13 (54%) of 24, and all participants were White. 11 (48%) of 23 patients in the rituximab group and five (21%) of 24 in the placebo group achieved glucocorticoid-free remission at 21 weeks (difference 27% [one-sided 95% CI 4]; relative risk 2·3 [1·1]; p=0·049). Ten infusion-related complaints occurred in the rituximab group versus three in the placebo group (relative rate 3·5 [one-sided 95% CI 1·3]). One serious adverse event occurred (pulmonary embolism; in the rituximab group), and there were no deaths. Rituximab was shown to be efficacious in combination with 17-week glucocorticoid treatment compared with glucocorticoid treatment alone in terms of glucocorticoid-free remission in patients with polymyalgia rheumatica. If these findings are confirmed by larger trials, rituximab could be a valuable glucocorticoid-sparing treatment for patients with polymyalgia rheumatica.

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

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. 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. 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. 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 Giant Cell Arteritis and Takayasu Arteritis.

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. 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. 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. 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.

Impact of age at diagnosis in polymyalgia rheumatica: A retrospective cohort study of 218 patients

Polymyalgia rheumatica (PMR) is a common musculoskeletal inflammatory disease that may occur with giant-cell arteritis (GCA) or in an isolated form. While the incidence is highest in the elderly, there is a paucity of data on its presentation, clinical course and response to treatment in younger individuals. We conducted a retrospective review of 40 patients who were diagnosed with isolated PMR under the age of 60 and 178 patients diagnosed above this age, taking into account clinical and laboratory data and treatment history. Patients who were diagnosed at a younger age had lower acute-phase reactant levels at diagnosis but not after initiation of treatment or at the time of relapse. The risk of relapse was lower in the group diagnosed under age 60 (35% vs 55%). Cumulative and maximal glucocorticoid doses, use of glucocorticoid-sparing agents and duration of glucocorticoid treatment, did not differ between the groups. In multivariate analysis, younger age at diagnosis was associated with cervical pain and male gender. Compared to patients diagnosed above age 60, patients diagnosed with PMR at a younger age have a lower risk of relapse, but similar long-term outcomes with regards to continued need for treatment.

49. Giant cell arteritis and Takayasu arteritis: two sides of the same coin in an elderly female?

49. Giant cell arteritis and Takayasu arteritis: two sides of the same coin in an elderly female?

Clinical Manifestations, Diagnosis, and Treatment of Sarcoidosis.

The focus of this review is current knowledge about the epidemiology, clinical manifestations, diagnosis, and treatment of both pulmonary sarcoidosis and extrapulmonary sarcoidosis. Although intrathoracic involvement is the hallmark of the disease, present in over 90% of patients, sarcoidosis can affect virtually any organ. Clinical presentations of sarcoidosis are diverse, ranging from asymptomatic, incidental findings to organ failure. Diagnosis requires the presence of noncaseating granuloma and compatible presentations after exclusion of other identifiable causes. Spontaneous remission is frequent, so treatment is not always indicated unless the disease is symptomatic or causes progressive organ damage/dysfunction. Glucocorticoids are the cornerstone of treatment of sarcoidosis even though evidence from randomized controlled studies is lacking. Glucocorticoid-sparing agents and biologic agents are often used as second- and third-line therapy for patients who do not respond to glucocorticoids or experience serious adverse effects.

2018 Update of the EULAR recommendations for the management of large vessel vasculitis

BackgroundSince the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have...

Management of large-vessel vasculitis.

Glucocorticoids are the mainstay of therapy for large-vessel vasculitis, but potential toxicity and frequent relapses led to studies with nonbiologic and biologic glucocorticoid-sparing agents. The aim of this review is to discuss the recent evidence for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK). Tocilizumab proved to be a powerful glucocorticoid-sparing agent for GCA in a randomized placebo-controlled trial, whereas the trials with tocilizumab and abatacept failed to show a significant difference from placebo in relapse-free survival rate in TAK. Further trials are awaiting for establishing the role of abatacept and ustekinumab for GCA, and rituximab and tumor necrosis factor inhibitors, including certolizumab for TAK, as well as nonbiologic agents for both indications. Despite recent randomized controlled trials with biologic agents, management of large-vessel vasculitis largely depends on observational studies. Well designed controlled trials using validated outcome measures in large number of patients, identification of biologic markers that could guide the choice of targeted treatments, and standardization of disease assessment including imaging modalities are unmet needs for the management of large-vessel vasculitis.