The role of biologics in the treatment of giant cell arteritis

ABSTRACT: Introduction: Giant cell arteritis is a vasculitis of large and middle-sized arteries that affects individuals older than 50 years. Although glucocorticoids remain the mainstay in the treatment of this vasculitis, other drugs are often required to achieve clinical remission and allow glucocorticoid discontinuation. Areas covered: The review summarizes the main biologic therapies used for the managements of GCA. Expert commentary: Although several biologic agents have been used in patients with GCA, the only biologic agent currently approved for this purpose is the recombinant humanized anti-IL-6 receptor antibody: tocilizumab. It has demonstrated efficacy to improve clinical symptoms, decrease the cumulative prednisone dose and reduce the frequency of relapses in clinical trials and real-life studies on patients with GCA. A trial showed that abatacept may be useful to maintain remission in GCA patients. An openlabel study suggested that ustekinumab could be useful for the treatment of patients with refractory GCA. However, further studies are required to confirm if both abatacept and ustekinumab are useful as an adjunctive therapy to reduce relapses or as a glucocorticoid sparing agent in GCA. Anakinra has been successfully used in a few patients with refractory GCA. In contrast, anti-tumor necrosis factor- α therapy yielded disappointing results in GCA

The Spectrum of Interstitial Lung Disease Associated With Autoimmune Diseases: Data of a 3.6-Year Prospective Study From a Referral Center of Interstitial Lung Disease and Lung Transplantation

Interstitial lung disease (ILD) may occur in patients with a rheumatic autoimmune disease (AD), increasing their risk of morbidity and mortality. However, little is known about the prevalence of AD in patients diagnosed with an ILD. In this prospective study, we determined the spectrum of ILD associated with AD (AD-ILD) among patients sent for assessment to a single clinic of ILD and lung transplantation from a referral center between May 2016 and December 2019. ILD diagnosis was made by pneumologists based on clinical and radiological findings and pulmonary function test abnormalities. All patients with ILD were also assessed by experienced rheumatologists. During the period of assessment, 338 patients were diagnosed with ILD. Among them, 32.8% fulfilled definitions for an AD. Most cases with AD-ILD had a diagnosis of rheumatoid arthritis (27.0%), systemic sclerosis (26.1%) or anti-synthetase syndrome (17.1%). Interestingly, 18% of the patients with AD-ILD were diagnosed as having an interstitial pneumonia with autoimmune features. Antinuclear antibodies and non-specific interstitial pneumonia were the most frequent positive autoantibodies and radiological pattern found in AD-ILD patients, respectively. In conclusion, our study indicates that a high number of ILD patients have a related AD. Consequently, close collaboration among rheumatologists and pneumologists is needed.This research received no external funding. SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (Instituto de Salud Carlos III, co-funded by the European Regional Development Fund)

Predictors of positive (18) F-FDG PET/CT-scan for large vessel vasculitis in patients with persistent polymyalgia rheumatica

Objective: Polymyalgia rheumatica (PMR) is often the presenting manifestation of giant cell arteritis (GCA). Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan often discloses the presence of large vessel vasculitis (LVV) in PMR patients. We aimed to identify predictive factors of a positive PET/CT scan for LVV in patients classified as having isolated PMR according to well-established criteria. Methods: A set of consecutive patients with PMR from a single hospital were assessed. All of them underwent PET/CT scan between January 2010 and February 2018 based on clinical considerations. Patients with PMR associated to other diseases, including those with cranial features of GCA, were excluded. The remaining patients were categorized in classic PMR (if fulfilled the 2012 EULAR/ACR classification criteria at disease diagnosis; n=84) or atypical PMR (who did not fulfill these criteria; n=16). Only information on patients with classic PMR was assessed. Results: The mean age of the 84 patients (51 women) with classic PMR was 71.4±9.2 years. A PET/CT scan was positive in 51(60.7%). Persistence of classic PMR symptoms was the most common reason to perform a PET/CT scan. Nevertheless, patients with positive PET/CT scan often had unusual symptoms. The best set of predictors of a positive PET/CT scan were bilateral diffuse lower limb pain (OR=8.8, 95% CI 1.7-46.3; p=0.01), pelvic girdle pain (OR=4.9, 95% CI 1.50-16.53; p=0.01) and inflammatory low back pain (OR=4.7, 95% CI 1.03-21.5; p=0.04). Conclusion: Inflammatory low back pain, pelvic girdle and diffuse lower limb pain are predictors of positive PET/CT scan for LVV in PMR

Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice

OBJECTIVE: Tocilizumab (TCZ) has shown efficacy in clinical trials on giant cell arteritis (GCA). Real-world data are scarce. Our objective was to assess efficacy and safety of TCZ in unselected patients with GCA in clinical practice Methods: Observational, open-label multicenter study from 40 national referral centers of GCA patients treated with TCZ due to inefficacy or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants, glucocorticoid-sparing effect, prolonged remission and relapses. A comparative study was performed: (a) TCZ route (SC vs. IV); (b) GCA duration (?6 vs. >6 months); (c) serious infections (with or without); (d) ?15 vs. >15 mg/day at TCZ onset. RESULTS: 134 patients; mean age, 73.0 ± 8.8 years. TCZ was started after a median [IQR] time from GCA diagnosis of 13.5 [5.0-33.5] months. Ninety-eight (73.1%) patients had received immunosuppressive agents. After 1 month of TCZ 93.9% experienced clinical improvement. Reduction of CRP from 1.7 [0.4-3.2] to 0.11 [0.05-0.5] mg/dL (p < 0.0001), ESR from 33 [14.5-61] to 6 [2-12] mm/1st hour (p < 0.0001) and decrease in patients with anemia from 16.4% to 3.8% (p < 0.0001) were observed. Regardless of administration route or disease duration, clinical improvement leading to remission at 6, 12, 18, 24 months was observed in 55.5%, 70.4%, 69.2% and 90% of patients. Most relevant adverse side-effect was serious infections (10.6/100 patients-year), associated with higher doses of prednisone during the first three months of therapy. CONCLUSION: In clinical practice, TCZ yields a rapid and maintained improvement of refractory GCA. Serious infections appear to be higher than in clinical trials

Tocilizumab in visual involvement of giant cell arteritis: a multicenter study of 471 patients

Background: Visual involvement is the most feared complication of giant cell arteritis (GCA). Information on the efficacy of tocilizumab (TCZ) for this complication is scarce and controversial. Objective: We assessed a wide series of GCA treated with TCZ, to evaluate its role in the prevention of new visual complications and its efficacy when this manifestation was already present before the initiation of TCZ. Design: This is an observational multicenter study of patients with GCA treated with TCZ. Methods: Patients were divided into two subgroups according to the presence or absence of visual involvement before TCZ onset. Visual manifestations were classified into the following categories: transient visual loss (TVL), permanent visual loss (PVL), diplopia, and blurred vision. Results: Four hundred seventy-one GCA patients (mean age, 74 +/- 9 years) were treated with TCZ. Visual manifestations were observed in 122 cases (26%), of which 81 were present at TCZ onset: PVL (n = 60; unilateral/bilateral: 48/12), TVL (n = 17; unilateral/bilateral: 11/6), diplopia (n = 2), and blurred vision (n = 2). None of the patients without previous visual involvement or with TVL had new episodes after initiation of TCZ, while only 11 out of 60 (18%) patients with PVL experienced some improvement. The two patients with diplopia and one of the two patients with blurred vision improved. Conclusion: TCZ may have a protective effect against the development of visual complications or new episodes of TVL in GCA. However, once PVL was established, only a few patients improved

Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice.

Tocilizumab (TCZ) has shown efficacy in clinical trials on giant cell arteritis (GCA). Real-world data are scarce. Our objective was to assess efficacy and safety of TCZ in unselected patients with GCA in clinical practice Methods: Observational, open-label multicenter study from 40 national referral centers of GCA patients treated with TCZ due to inefficacy or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants, glucocorticoid-sparing effect, prolonged remission and relapses. A comparative study was performed: (a) TCZ route (SC vs. IV); (b) GCA duration (≤6 vs. >6 months); (c) serious infections (with or without); (d) ≤15 vs. >15 mg/day at TCZ onset. 134 patients; mean age, 73.0 ± 8.8 years. TCZ was started after a median [IQR] time from GCA diagnosis of 13.5 [5.0-33.5] months. Ninety-eight (73.1%) patients had received immunosuppressive agents. After 1 month of TCZ 93.9% experienced clinical improvement. Reduction of CRP from 1.7 [0.4-3.2] to 0.11 [0.05-0.5] mg/dL (p  In clinical practice, TCZ yields a rapid and maintained improvement of refractory GCA. Serious infections appear to be higher than in clinical trials