Current Perspectives in Giant Cell Arteritis: Can We Better Connect Pathogenesis and Treatment?

Giant cell arteritis (GCA) is a large-vessel vasculitis affecting elderly patients and targeting the aorta and its main branches, leading to cranial and extracranial manifestations. The mechanism behind the ischemia is a granulomatous-type inflammation with potentially critical lesions, including visual loss involving the ophthalmic artery. Despite significant progress in unraveling the pathophysiology of this disease, treatment options still rely on glucocorticoids (GCs) to overcome active vascular lesions and disease flares. However, uncertainty still revolves around the optimal dose and tapering rhythm. Few corticosteroid-sparing agents have proven useful in GCA, namely, methotrexate and tocilizumab, benefiting cumulative GC dose and relapse-free intervals. The future looks promising with regard to using other agents like abatacept and Janus-kinase inhibitors or blocking the granulocyte-macrophage colony-stimulating factor receptor.

Performance of a fast-track pathway for giant cell arteritis in Waikato, Aotearoa New Zealand.

AIMS: Giant cell arteritis (GCA) is the most common primary vasculitis in adults over 50 years of age. To facilitate early diagnosis and reduce harms from corticosteroids and temporal artery biopsies, fast-track pathways have been established. We review the benefits of the fast-track pathway set up in Waikato, Aotearoa New Zealand. METHODS: Patients were collected prospectively as part of the fast-track pathway from 2014 to 2022. Their records were then reviewed retrospectively to collect data on clinical features, investigations and treatment. RESULTS: There were 648 individual patients over the study period who had a colour Doppler ultrasound (CDUS) of the temporal arteries. There were 17 true positive CDUS, giving a sensitivity of 10.3% (95% confidence interval [CI] 6.3-15.5%) and specificity of 99.8% (95% CI 99.1-100%). Patients with GCA and a positive scan had significantly fewer steroids than those with GCA and a negative scan (p=0.0037). There were 376 patients discharged after a CDUS who did not have a diagnosis of GCA, resulting in reduced corticosteroid and temporal artery biopsy exposure. CONCLUSIONS: This is a real-life study that reflects the benefits of fast-track pathways in Aotearoa New Zealand to patients and healthcare systems. It also shows the effect of corticosteroids on positive CDUS, an important consideration when setting up an fast-track pathway.

Eosinophilic giant cell arteritis: A different subset of disease?

OBJECTIVES: To describe the clinical findings, response to therapy and course of patients with transmural eosinophilic infiltration at temporal artery biopsy (TAB). METHODS: The study consisted of a retrospective cohort of 254 consecutive GCA patients with evidence of transmural inflammation at TAB seen at the Santa Maria Nuova Hospital over a 28-year period. The findings of the 22 patients with eosinophilic infiltration (≥ 20 eosinophils/hpf) at TAB were compared with those of 232 patients without. Among these 232 patients, we sampled 42 GCA patients matched for age, sex and follow-up duration to the 22 with eosinophilic infiltration, to compare allergic manifestations. RESULTS: GCA patients with eosinophilic infiltration compared to those without presented more frequently cranial symptoms (p = 0.052), headaches (p = 0.005), abnormalities of TAs at physical examination (p = 0.045), jaw claudication (p = 0.024), and systemic manifestations (p = 0.016) and had higher CRP levels at diagnosis (p = 0.001). Regarding histological lesions, a severe transmural inflammation, laminar necrosis and intraluminal acute thrombosis were more frequently observed in patients with eosinophilic infiltration (p = 0.066, p < 0.001, and p = 0.010, respectively). Long-term remission and flares were similar in the two groups. When 21 GCA patients with eosinophilic infiltration were compared to 42 without, blood eosinophilic counts at diagnosis were normal and no patients had evidence or developed allergic manifestations and/or clinical findings of systemic necrotizing vasculitis. CONCLUSION: Patients with transmural eosinophilic infiltration represent a subset of GCA with cranial disease and more severe inflammation.

Giant Cell Arteritis: Advances in Understanding Pathogenesis and Implications for Clinical Practice.

Giant cell arteritis (GCA) is a noninfectious granulomatous vasculitis of unknown etiology affecting individuals older than 50 years. Two forms of GCA have been identified: a cranial form involving the medium-caliber temporal artery causing temporal arteritis (TA) and an extracranial form involving the large vessels, mainly the thoracic aorta and its branches. GCA generally affects individuals with a genetic predisposition, but several epigenetic (micro)environmental factors are often critical for the onset of this vasculitis. A key role in the pathogenesis of GCA is played by cells of both the innate and adaptive immune systems, which contribute to the formation of granulomas that may include giant cells, a hallmark of the disease, and arterial tertiary follicular organs. Cells of the vessel wall cells, including vascular smooth muscle cells (VSMCs) and endothelial cells, actively contribute to vascular remodeling responsible for vascular stenosis and ischemic complications. This review will discuss new insights into the molecular and cellular pathogenetic mechanisms of GCA, as well as the implications of these findings for the development of new diagnostic biomarkers and targeted drugs that could hopefully replace glucocorticoids (GCs), still the backbone of therapy for this vasculitis.

Effect of combined treatment with prednisone and methotrexate versus prednisone alone over laboratory parameters in giant cell arteritis / Efecto del tratamiento combinado con prednisona y metotrexato versus prednisona sola sobre los parámetros de laboratorio en arteritis de células gigantes

Objective: To compare the effect of combined treatment with prednisone and methotrexate (MTX) versus prednisone alone over laboratory parameters in giant cell arteritis (GCA). Patients and methods: We performed a double-blind, placebo-controlled, randomized clinical trial about usefulness of treatment with prednisone and MTX versus prednisone and placebo in GCA (Ann Intern Med 2001;134:106–114). As a part of follow-up of patients (n=42), we performed laboratory analysis in 20 time points during the two-year period of follow-up. To analyze differences, we calculated the area under the curve (AUC) for erythrocyte sedimentation rate (ESR), hemoglobin, and platelets, and compared the results in both groups adjusting by time of follow-up, existence of relapses and dose of prednisone. Results: A total of 724 laboratory measurements were done. Median value of ESR was 33 [18–56] in patients with placebo and 26 [15–44] in patients with MTX (P=0.0002). No significant differences were observed in ESR during relapses. The mean ESR value followed a parallel course in both groups, but was lower in the group with MTX than in the group with placebo in 18 of 20 time points of follow-up. The AUC of ESR by time of follow-up was 28,461.7±12,326 in the group with placebo and 19,598.4±8,117 in the group with MTX (mean difference 8,863, 95% CI 1.542–16.184; P=0.019). The course of other laboratory parameters paralleled, without statistical significance, those observed for ESR. Conclusions: These data, along with clinical data, suggest that MTX might play a role as a disease-modifying agent in the treatment of GCA.(AU)

Objetivo: Comparar el efecto del tratamiento combinado con prednisona y metotrexato (MTX) versus prednisona sola sobre parámetros de laboratorio en arteritis de células gigantes (ACG). Pacientes y métodos: Realizamos un ensayo clínico aleatorizado, doble ciego, controlado con placebo sobre la utilidad del tratamiento con prednisona y MTX frente a prednisona y placebo en la ACG (Ann Intern Med. 2001;134:106-114). Como parte del seguimiento de los pacientes (n=42), realizamos análisis de laboratorio en 20 puntos temporales durante el período de seguimiento de 2 años. Para analizar diferencias calculamos el área bajo la curva (AUC) de VSG, hemoglobina y plaquetas, y comparamos los resultados en ambos grupos ajustando por tiempo de seguimiento, existencia de recaídas y dosis de prednisona. Resultados: Se realizaron un total de 724 mediciones de laboratorio. El valor medio de la VSG fue de 33 (18-56) en pacientes con placebo y de 26 (15-44) en pacientes con MTX (p=0,0002). No se observaron diferencias significativas en la VSG durante las recaídas. El valor medio de la VSG siguió un curso paralelo en ambos grupos, pero fue menor en el grupo con MTX que en el grupo con placebo en 18 de 20 puntos temporales de seguimiento. El AUC de la VSG por tiempo de seguimiento fue de 28.461,7±12.326 en el grupo con placebo y de 19.598,4±8.117 en el grupo con MTX (diferencia de medias 8.863; IC 95%: 1.542-16.184; p=0,019). La evolución de los demás parámetros de laboratorio fue paralela, sin significación estadística, a la observada para la VSG. Conclusiones: Estos datos, junto con los datos clínicos, sugieren que el MTX podría desempeñar un papel como agente modificador de la enfermedad en el tratamiento de la ACG.(AU)

Effect of combined treatment with prednisone and methotrexate versus prednisone alone over laboratory parameters in giant cell arteritis.

OBJECTIVE: To compare the effect of combined treatment with prednisone and methotrexate (MTX) versus prednisone alone over laboratory parameters in giant cell arteritis (GCA). PATIENTS AND METHODS: We performed a double-blind, placebo-controlled, randomized clinical trial about usefulness of treatment with prednisone and MTX versus prednisone and placebo in GCA (Ann Intern Med 2001;134:106-114). As a part of follow-up of patients (n=42), we performed laboratory analysis in 20 time points during the two-year period of follow-up. To analyze differences, we calculated the area under the curve (AUC) for erythrocyte sedimentation rate (ESR), hemoglobin, and platelets, and compared the results in both groups adjusting by time of follow-up, existence of relapses and dose of prednisone. RESULTS: A total of 724 laboratory measurements were done. Median value of ESR was 33 [18-56] in patients with placebo and 26 [15-44] in patients with MTX (P=0.0002). No significant differences were observed in ESR during relapses. The mean ESR value followed a parallel course in both groups, but was lower in the group with MTX than in the group with placebo in 18 of 20 time points of follow-up. The AUC of ESR by time of follow-up was 28,461.7±12,326 in the group with placebo and 19,598.4±8,117 in the group with MTX (mean difference 8,863, 95% CI 1.542-16.184; P=0.019). The course of other laboratory parameters paralleled, without statistical significance, those observed for ESR. CONCLUSIONS: These data, along with clinical data, suggest that MTX might play a role as a disease-modifying agent in the treatment of GCA.

[Polymyalgia rheumatica-A challenge in geriatrics : Interdisciplinary presentation of diagnostics and treatment]. / Polymyalgia rheumatica ­ eine Herausforderung in der Altersmedizin : Diagnostik und Therapie interdisziplinär dargestellt.

Polymyalgia rheumatica is the second most frequent inflammatory rheumatic disease in people aged over 50 years, after rheumatoid arthritis. It is characterized by pain and morning stiffness in the region of the shoulders, hip girdle and neck. It can be associated with giant cell arteritis (CGA). Treatment with glucocorticoids is indispensable. The duration of treatment varies and often exceeds 1 year. The additive administration of methotrexate is an option for saving glucocorticoids. The biologicals tocilizumab or secukinumab are very promising alternatives. The course of treatment should be closely monitored for inflammation parameters, glucocorticoid side effects, pain, visual acuity, depression, activities of daily living and especially related to functions of the upper extremities. The geriatric assessment plays an important role in the management of this condition.

The Meteoritics Trial: efficacy of methotrexate after remission-induction with tocilizumab and glucocorticoids in giant cell arteritis-study protocol for a randomized, double-blind, placebo-controlled, parallel-group phase II study.

BACKGROUND: Glucocorticoids (GC) are the standard treatment for giant cell arteritis (GCA), even though they are associated with adverse side effects and high relapse rates. Tocilizumab (TCZ), an interleukin-6 receptor antagonist, has shown promise in sustaining remission and reducing the cumulative GC dosage, but it increases the risk of infections and is expensive. After discontinuation of TCZ, only about half of patients remain in remission. Additionally, only few studies have been conducted looking at remission maintenance, highlighting the need for alternative strategies to maintain remission in GCA. Methotrexate (MTX) has been shown to significantly decrease the risk of relapse in new-onset GCA and is already a proven safe drug in many rheumatologic diseases. METHODS: This study aims to evaluate the efficacy and safety of MTX in maintaining remission in patients with GCA who have previously been treated with GC and at least 6 months with TCZ. We hypothesize that MTX can maintain remission in GCA patients, who have achieved stable remission after treatment with GC and TCZ, and prevent the occurrence of relapses. The study design is a monocentric, randomized, double-blind, placebo-controlled, parallel-group phase II trial randomizing 40 GCA patients 1:1 into a MTX or placebo arm. Patients will receive 17.5 mg MTX/matching placebo weekly by subcutaneous injection for 12 months, with the possibility of dose reduction if clinically needed. A 6-month follow-up will take place. The primary endpoint is the time to first relapse in the MTX group versus placebo during the 12-month treatment period. Secondary outcomes include patient- and investigator-reported outcomes and laboratory findings, as well as the prevalence of aortitis, number of vasculitic vessels, and change in intima-media thickness during the study. DISCUSSION: This is the first clinical trial evaluating remission maintenance of GCA with MTX after a previous treatment cycle with TCZ. Following the discontinuation of TCZ in GCA, MTX could be a safe and inexpensive drug. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05623592. Registered on 21 November 2022. EU Clinical Trials Register, 2022-501058-12-00. German Clinical Trials Register DRKS00030571.

Trends in health care of patients with vasculitides, including giant cell arteritis, Takayasu arteritis, ANCA-associated vasculitis and Behçet's disease: cross-sectional data of the German National Database 2007-2021.

The aim of this study is to present the current care situation of patients with giant cell arteritis (GCA), Takayasu arteritis (TAK), ANCA-associated vasculitis (AAV) and Behçet's disease (BD). Trends over the last 15 years will reflect improvements and remaining deficits in the management of vasculitides. Consecutive cross-sectional data from patients with vasculitides from the German National Database (NDB) of the Collaborative Arthritis Centres between 2007 and 2021 were included. Medication, physician- and patient-reported outcomes on disease activity and disease burden, inpatient stays and occupational participation are compared for different vasculitis entities and over time. Employment rates were compared to German population rates. Between 502 and 854 vasculitis patients were annually documented. GCA and AAV were the most common vasculitides. Median disease duration ranged from 2 to 16 years. Over the years, glucocorticoids decreased in proportion and dose, most markedly in GCA and TAK, while biologic therapies increased up to 27%. Physicians rated disease activity as low for the vast majority of patients, while patients-reported moderate outcomes in many dimensions. PROs remained largely unchanged. The proportion of employed patients (< 65 years) increased from 47 to 57%. In recent years, biologics are increasingly used in patients with vasculitides, while glucocorticoids decreased significantly. PRO's have not improved. Work participation increased but remains lower than that in the German population.

Review of phase 2/3 trials in polymyalgia rheumatica and giant cell arteritis.

INTRODUCTION: GCA (giant cell arteritis) and PMR (polymyalgia rheumatica) are two overlapping inflammatory rheumatic conditions that are seen exclusively in older adults, sharing some common features. GCA is a clinical syndrome characterized by inflammation of the medium and large arteries, with both cranial and extracranial symptoms. PMR is a clinical syndrome characterized by stiffness in the neck, shoulder, and pelvic girdle muscles. Both are associated with constitutional symptoms. AREAS COVERED: In this review, we assess the established and upcoming treatments for GCA and PMR. We review the current treatment landscape, completed trials, and upcoming trials in these conditions, to identify new and promising therapies. EXPERT OPINION: Early use of glucocorticoids (GC) remains integral to the immediate management of PMR and GCA but being aware of patient co-morbidities that may influence treatment toxicity is paramount. As such GC sparing agents are required in the treatment of PMR. Currently there are limited treatment options available for PMR and GCA, and significant unmet needs remain. Newer mechanisms of action, and hence therapeutic options being studied include CD4 T cell co-stimulation blockade, IL-17 inhibition, IL-12/23 inhibition, GM-CSF inhibition, IL-1ß inhibition, TNF-α antagonist and Jak inhibition, among others, which will be discussed in this review.

Treatment of giant cell arteritis with ultra-short glucocorticoids and tocilizumab: the role of imaging in a prospective observational study.

OBJECTIVES: To assess the impact of tocilizumab (TCZ) monotherapy after ultra-short-pulse glucocorticoids (GCs) on clinical manifestations, and vessel inflammation and damage in large vessel-GCA (LV-GCA). METHODS: In this prospective observational study, we enrolled patients with active LV-GCA. All patients received 500 mg per day i.v. methylprednisolone for three consecutive days and weekly s.c. TCZ injections from day 4 until week 52. PET/CT was performed on all patients at baseline and at weeks 24 and 52. The primary end points were the reduction in the PET vascular activity score (PETVAS) at weeks 24 and 52 compared with baseline, and the proportion of patients with relapse-free remission at weeks 24 and 52. The secondary end point was the proportion of patients with new aortic dilation at weeks 24 and 52. RESULTS: A total of 18 patients were included (72% female, mean age 68.5 years). Compared with the baseline value, a significant reduction in the PETVAS was observed at weeks 24 and 52, mean (95% CI) reductions -8.6 (-11.5 to -5.7) and -10.4 (-13.6 to -7.2), P = 0.001 and 0.002, respectively. The proportion of patients with relapse-free remission at weeks 24 and 52 was 10/18 (56%, 95% CI 31-78) and 8/17 (47%, 95% CI 23-72), respectively. At weeks 24 and 52, no patient had shown new aortic dilation. However, 4 patients who had shown aortic dilation at baseline showed a significant increase in aortic diameter (≥5 mm) at week 52. CONCLUSION: TCZ monotherapy after ultra-short-pulse GCs controlled the clinical symptoms of GCA and reduced vascular inflammation. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05394909.

Risk Factors for Relapse and/or Prolonged Glucocorticoid Therapy in Polymyalgia Rheumatica: Multicenter Study in 185 Patients.

BACKGROUND: In polymyalgia rheumatica (PMR) relapses and long-term GC dependency are common. We assessed risk factors for higher relapse rate and/or prolonged glucocorticoid therapy in PMR patients. METHODS: A multicenter and observational study (chart review) of PMR patients seen between 2006 and 2021 who had at least a 3-month follow-up period after starting GCs was performed. Results were expressed as median and interquartile range 25th-75th or mean ± standard deviation for numerical variables and percentage for categorical ones. Relapse versus nonrelapse groups were compared using Cox proportional analysis. Hazards ratios (HRs) with 95% confidence intervals (CIs) are reported. In all cases, a p value <0.05 was considered to indicate statistical significance. RESULTS: We included 185 patients (69.1% female). The median follow-up time was 17.1 months (interquartile range, 6.8-34.7). Incidence of relapses was 1.2 per 100 persons/month. In univariate analysis, PMR patients with a previous history of dyslipidemia had a lower risk of relapse (HR, 0.55; 95% CI, 0.33-0.94; p = 0.03); high-dose GC (HR, 2.35; 95% CI, 1.42-3.87; p = 0.001) and faster GC dose reduction had higher risk of relapse (HR, 3.04; 95% CI, 1.77-5.21; p = 0.001). In multivariate analysis, a previous history of dyslipidemia had a lower risk of relapse (HR, 0.54; 95% CI, 0.32-0.92; p = 0.023), and high dose of GC (HR, 2.46; 95% CI, 1.49-4.08; p = 0.001) remained the only risk factors for relapse. CONCLUSIONS: Lower doses of corticosteroids and a slow rate of reduction are critical to avoid relapse in PMR. Risk factors for higher relapse rate rely on therapy more than clinical characteristics of the patients at the time of diagnosis of PMR.

Humoral SARS-CoV-2 Vaccine Responses in Patients With Giant Cell Arteritis and Polymyalgia Rheumatica: Decay After Primary Vaccination and Effects of the Booster.

OBJECTIVE: Vaccination remains essential in preventing morbidity of SARS-CoV-2 infections. We previously showed that >10 mg/day of prednisolone and methotrexate was associated with reduced antibody concentrations after primary vaccination in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). This follow-up study was undertaken to measure the decay of antibody concentrations and the immunogenicity of SARS-CoV-2 booster vaccination. METHODS: Patients with GCA/PMR included in the primary vaccination (BNT162b2 [Pfizer-BioNTech] or ChAdOx1 [Oxford/AstraZeneca]) study were asked again to donate blood samples 6 months after primary vaccination (n = 24) and 1 month after booster vaccination (n = 46, BNT162b2 or mRNA1273). Data were compared to those of age-, sex-, and vaccine-matched controls (n = 58 and n = 42, respectively). Multiple linear regression was performed with post-booster antibody concentrations as dependent variable and post-primary vaccination antibodies, prednisolone >10mg/day, and methotrexate use as predicting variables. RESULTS: Antibody concentrations decreased faster over time in GCA/PMR patients than in controls, which was associated with prednisolone treatment during primary vaccination. Post-booster antibody concentrations were comparable between patients and controls. Antibody concentrations post primary vaccination, but not treatment during booster vaccination, were predictive for antibody concentrations post booster vaccination. CONCLUSION: These results indicate that the decay of humoral immunity after primary vaccination is associated with prednisolone treatment, whereas the subsequent increase after booster vaccination, was not. Patients with low antibody concentrations following primary vaccination remained at an immunogenic disadvantage after a single booster vaccination. This longitudinal study in GCA/PMR patients stresses the importance of repeated booster vaccination for patients with poor responses to primary vaccination.

New Therapeutic Approaches to Large-Vessel Vasculitis.

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are large-vessel vasculitides affecting the aorta and its branches. Arterial damage from these diseases may result in ischemic complications, aneurysms, and dissections. Despite their similarities, the management of GCA and TAK differs. Glucocorticoids are used frequently but relapses are common, and glucocorticoid toxicity contributes to significant morbidity. Conventional immunosuppressive therapies can be beneficial in TAK, though their role in the management of GCA remains unclear. Tumor necrosis factor inhibitors improve remission rates and appear to limit vascular damage in TAK; these agents are not beneficial in GCA. Tocilizumab is the first biologic glucocorticoid-sparing agent approved for use in GCA and also appears to be effective in TAK. A better understanding of the pathogenesis of both conditions and the availability of targeted therapies hold much promise for future management.

Subclinical giant cell arteritis increases the risk of relapse in polymyalgia rheumatica.

OBJECTIVE: The aim of the present study was to determine the clinical significance of subclinical giant cell arteritis (GCA) in polymyalgia rheumatica (PMR) and ascertain its optimal treatment approach. METHODS: Patients with PMR who fulfilled the 2012 European Alliance of Associations for Rheumatology/American College of Rheumatology Provisional Classification Criteria for PMR, did not have GCA symptoms and were routinely followed up for 2 years and were stratified into two groups, according to their ultrasound results: isolated PMR and PMR with subclinical GCA. The outcomes (relapses, glucocorticoid use and disease-modifying antirheumatic drug treatments) between groups were compared. RESULTS: We included 150 patients with PMR (50 with subclinical GCA) with a median (IQR) follow-up of 22 (20-24) months. Overall, 47 patients (31.3 %) had a relapse, 31 (62%) in the subclinical GCA group and 16 (16%) in the isolated PMR group (p<0.001). Among patients with subclinical GCA, no differences were found in the mean (SD) prednisone starting dosage between relapsed and non-relapsed patients (32.4±15.6 vs 35.5±12.1 mg, respectively, p=0.722). Patients with subclinical GCA who relapsed had a faster prednisone dose tapering in the first 3 months compared with the non-relapsed patients, with a mean dose at the third month of 10.0±5.2 versus 15.2±7.9 mg daily (p<0.001). No differences were found between relapsing and non-relapsed patients with subclinical GCA regarding age, sex, C reactive protein and erythrocyte sedimentation rate. CONCLUSIONS: Patients with PMR and subclinical GCA had a significantly higher number of relapses during a 2-year follow-up than patients with isolated PMR. Lower starting doses and rapid glucocorticoid tapering in the first 3 months emerged as risk factors for relapse.

Evidence on treat to target strategies in polymyalgia rheumatica and giant cell arteritis: a systematic literature review.

OBJECTIVES: To inform an international task force about current evidence on Treat to Target (T2T) strategies in PMR and GCA. METHODS: A systematic literature research (SLR) was conducted in Medline, EMBASE, Cochrane Library, clinicaltrials.gov from their inception date to May 2022, and in the EULAR/ACR abstract database (2019-2021). Randomised clinical trials (RCTs) and non-randomised interventional studies published in English and answering at least one of the eleven PICO questions on T2T strategies, treatment targets and outcomes, framed by the taskforce, were identified. Study selection process, data extraction and risk of bias assessment were conducted independently by two investigators. RESULTS: Of 7809 screened abstracts, 397 were selected for detailed review and 76 manuscripts were finally included (31 RCTs, eight subgroup/exploratory analyses of RCTs and 37 non-randomised interventional studies). No study comparing a T2T strategy against standard of care was identified. In PMR RCTs, the most frequently applied outcomes concerned treatment (90.9% of RCTs), particularly the cumulative glucocorticoids (GC) dose and GC tapering, followed by clinical, laboratory and safety outcomes (63.3% each). Conversely, the most commonly reported outcomes in RCTs in GCA were prevention of relapses (72.2%), remission as well as treatment-related and safety outcomes (67.0% each). CONCLUSIONS: This SLR provides evidence and highlights the knowledge gaps on T2T strategies in PMR and GCA, informing the task force developing T2T recommendations for these diseases.

BOB-ACG study: Pulse methylprednisolone to prevent bilateral ophthalmologic damage in giant cell arteritis. A multicentre retrospective study with propensity score analysis.

INTRODUCTION: Giant cell arteritis (GCA) is complicated in 10 to 20% of cases by permanent visual ischemia (PVI). International guidelines advocate the use of intravenous pulse of methylprednisolone from 250 to 1000mg per day, for three days, followed by oral prednisone at 1mg/kg per day. The aim of this study is to assess whether this strategy significantly reduces the risk of early PVI of the second eye, compared with direct prednisone at 1mg/kg per day. METHODS: We conducted a multicentre retrospective observational study over the past 15 years in 13 French hospital centres. Inclusion criteria included: new case of GCA; strictly unilateral PVI, prednisone at dose greater than or equal to 0.9mg/kg per day; for the intravenous methylprednisolone (IV-MP) group, total dose between 900 and 5000mg, close follow-up and knowledge of visual status at 1 month of treatment, or earlier, in case of contralateral PVI. The groups were compared on demographic, clinical, biological, iconographic, and therapeutic parameters. Statistical analysis was optimised using propensity scores. RESULTS: One hundred and sixteen patients were included, 86 in the IV-MP group and 30 in the direct prednisone group. One patient in the direct prednisone group and 13 in the IV-MP group bilateralised, without significant difference between the two strategies (3.3% vs 15.1%). Investigation of the association between IV-MP patients and contralateral PVI through classical logistic regression, matching or stratification on propensity score did not show a significant association. Weighting on propensity score shows a significant association between IV-MP patients and contralateral PVI (OR=12.9 [3.4; 94.3]; P<0.001). Improvement in visual acuity of the initially affected eye was not significantly associated with IV-MP (visual acuity difference 0.02 vs -0.28 LogMar), even in the case of early management, i.e., within the first 48hours after the onset of PVI (n=61; visual acuity difference -0.11 vs 0.25 LogMar). Complications attributable to corticosteroid therapy in the first month were significantly more frequent in the IV-MP group (31.8 vs 10.7%; P<0.05). DISCUSSION: Our data do not support the routine use of pulse IV-MP for GCA complicated by unilateral PVI to avoid bilateral ophthalmologic damage. It might be safer to not give pulse IV-MP to selected patients with high risks of glucocorticoids pulse side effects. A prospective randomised multicentre study comparing pulse IV-MP and prednisone at 1mg/kg per day is desirable.