scholarly journals Assessment of the efficacy and safety of tocilizumab in patients over 80 years old with giant cell arteritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Hubert de Boysson ◽  
◽  
Maelle Le Besnerais ◽  
Félix Blaison ◽  
Aurélie Daumas ◽  
...  

Abstract Objective To assess the efficacy and tolerance of tocilizumab (TCZ) in giant cell arteritis (GCA) patients over 80. Method GCA patients over 80 years old from the French Study Group for Large Vessel Vasculitis register who received TCZ were analyzed. Results Twenty-one GCA patients (median age 84 [81–90] years old, including nine over 85) received TCZ for the following nonexclusive reasons: glucocorticoid (GC)-sparing effect in 14, relapsing disease in 8, disease severity in 4, and/or failure of another immunosuppressant in 4. TCZ was introduced with GCs at diagnosis in 6 patients and at 8 [3–37] months after GC initiation in 15 others. After a median delay of 8 [2–21] months post-TCZ introduction, 14 (67%) patients were able to definitively stop GCs, including 6 who were GC-dependent before TCZ. At the last follow-up (median 20 [3–48] months), 11 (52%) patients had definitively stopped TCZ, and 2 additional patients had stopped but relapsed and resumed TCZ. Seven (33%) patients experienced 11 adverse events: hypercholesterolemia in 4 patients; infections, i.e., pyelonephritis, bronchitis, and fatal septic shock associated with mesenteric infarction following planned surgery (GCs were stopped for 1 year and TCZ infusions for 2 months), respectively, in 3 patients; moderate thrombocytopenia and moderate neutropenia in 2 patients; and a 5-fold increase in transaminase levels in another that improved after TCZ dose reduction. Conclusion TCZ remains a valuable GC-sparing option in the oldest GCA patients with an interesting risk-benefit ratio. Mild-to-moderate adverse events were observed in one-third of patients.

Rheumatology ◽  
2021 ◽  
Author(s):  
Verena Schönau ◽  
Jessica Roth ◽  
Koray Tascilar ◽  
Giulia Corte ◽  
Bernhard Manger ◽  
...  

Abstract Objectives Efficacy evaluation of giant cell arteritis (GCA) treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT. Methods Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with methotrexate (MTX) or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients. Results We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX, and 19 with TOC. PETVAS decreased from 18.9–8.0 units at follow-up in the overall population (p< 0.001). PETVAS changes were numerically higher in patients receiving MTX (-12.3 units) or TOC (-11.7 units) compared with PRED (-8.7). Mean cumulative prednisolone dosages were 5637, 4418, and 2984 mg in patients treated with PRED, MTX, and TOC (p= 0.002). Risk ratios for glucocorticoid discontinuation at the time of follow-up PET/CT were 6.77 (95%CI 1.01–45.29; p= 0.049) and 16.25 (95%CI 2.60–101.73; p= 0.003) for MTX and TOC users compared with PRED users. Conclusion Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX, and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 397.1-397
Author(s):  
S. Deshayes ◽  
K. Ly ◽  
V. Rieu ◽  
G. Maigné ◽  
N. M. Silva ◽  
...  

Background:The treatment of giant cell arteritis (GCA) relies on corticosteroids but is burdened by a high rate of relapses and adverse effects. Anti-interleukin-6 treatments show a clear benefit with a significant steroid-sparing effect, but late relapses occur after treatment discontinuation. In addition to interleukin-6, interleukin-1 also appears to play a significant role in GCA pathophysiology.Objectives:We report herein the efficacy of anakinra, an interleukin-1 receptor antagonist, in 6 GCA patients exhibiting corticosteroid dependence or resistance, specifically analyzing the outcome of aortitis in 4 of them, and including the long-term follow-up of 2 previously described patients (1).Methods:This retrospective study analyzed the cases of all GCA patients treated with anakinra from the French Study Group for Large Vessel Vasculitis.Patients had to satisfy the following two criteria to be enrolled in this retrospective study. First, their diagnosis of GCA should be based on the fulfillment of at least 3 criteria of the American College of Rheumatology (ACR) for GCA or on the satisfaction of 2 of these criteria along with the demonstration of LVI on imaging. Second, patients should have received anakinra because of corticosteroid dependence or resistance.Corticosteroid dependence was defined as ≥2 relapses or the combination of 2 of the following criteria: a daily dose of oral prednisone >20 mg/day (or 0.3 mg/kg) at 6 months; a daily dose of oral prednisone >10 mg/day (or 0.2 mg/kg) at 12 months; and/or a treatment maintained >24 months because of a relapsing disease course. Corticosteroid resistance was defined as persistent increased inflammatory parameters at month 3 despite a steroid dosage over 0.5 mg/kg.Results:After a median duration of anakinra therapy of 19 [18–32] months, all 6 patients exhibited complete clinical and biological remission. Among the 4 patients with large-vessel involvement, 2 had a disappearance of aortitis under anakinra, and 2 showed a decrease in vascular uptake. After a median follow-up of 56 [48–63] months, corticosteroids were discontinued in 4 patients, and corticosteroid dosage could be decreased to 5 mg/day in 2 patients. One patient relapsed 13 months after anakinra introduction in the context of increasing the daily anakinra injection interval to every 48 hours. Three patients experienced transient injection-site reactions, and 1 patient had pneumonia.Figure 1.Steroid dosages before and after the introduction of anakinra in 6 patients with giant-cell arteritis and corticosteroid dependence or resistance. The black arrow indicates the time of anakinra introduction.Conclusion:In this short series, anakinra appears to be an efficient and safe steroid-sparing agent in refractory GCA, with a possible beneficial effect on large-vessel involvement.References:[1]Ly K-H, Stirnemann J, Liozon E, Michel M, Fain O, Fauchais A-L. Interleukin-1 blockade in refractory giant cell arteritis. Joint Bone Spine 2014;81:76–8.Disclosure of Interests:Samuel Deshayes: None declared, Kim LY: None declared, Virginie Rieu: None declared, Gwénola Maigné: None declared, Nicolas Martin Silva: None declared, Alain Manrique: None declared, Jacques Monteil: None declared, Hubert de Boysson Speakers bureau: Roche-Chugai, Grant/research support from: Roche-Chugai, Achille Aouba Grant/research support from: SOBI


2016 ◽  
Vol 43 (8) ◽  
pp. 1547-1552 ◽  
Author(s):  
Alexis Régent ◽  
Serge Redeker ◽  
Alban Deroux ◽  
Pierre Kieffer ◽  
Kim Heang Ly ◽  
...  

Objective.To report the efficacy and safety of tocilizumab (TCZ) for giant cell arteritis (GCA).Methods.A retrospective multicenter study that included 34 patients receiving TCZ for GCA.Results.TCZ was effective in all but 6 patients, who still had mild symptoms. Mean glucocorticoid dose was tapered. One patient died and 3 patients had to stop TCZ therapy because of severe adverse events. Twenty-three patients stopped treatment; 8 of these experienced relapses after a mean of 3.5 ± 1.3 months.Conclusion.TCZ is effective in GCA. However, side effects occur. Whether this treatment has only a suspensive effect remains to be determined.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 655.1-655
Author(s):  
J. Rakholiya ◽  
M. Koster ◽  
H. Langenfeld ◽  
C. S. Crowson ◽  
A. Abril ◽  
...  

Background:Giant cell arteritis (GCA) is an inflammatory condition of medium- and large-sized arteries. Prospective clinical trials have demonstrated the efficacy of tocilizumab (TCZ) for treatment of patients with GCA (1). However, there is a limited data on the use of TCZ in routine clinical practice.Objectives:To evaluate the efficacy and safety of TCZ in a retrospective cohort study of patients with GCA treated with TCZ.Methods:Patients with GCA treated with TCZ at 4 clinical centers of a single tertiary care institution (2000-2020) were identified. The diagnosis of GCA was confirmed by at least one of the following modalities: 1. Arterial biopsy 2. Large vessel imaging 3. Clinical diagnosis of GCA meeting ACR classification criteria and established by a rheumatologist. Patient demographics, clinical presentation, laboratory studies, treatment course and adverse events were abstracted from the medical record; only patients with at least 6 months of follow-up after TCZ initiation were included. Kaplan-Meier methods were used to estimate time to TCZ discontinuation and time to first relapse after TCZ discontinuation. Poisson regression models were used to compare relapse rates before and after TCZ initiation.Results:The study cohort included 119 patients [61% female; mean (SD) age at GCA diagnosis 70.3 (8.2) years]. The majority of patients (89%) had a biopsy-proven and/or imaging-based diagnosis of GCA, while 13 (11%) had a clinical diagnosis of GCA. In addition to glucocorticoids, 40 (34%) patients received other immunosuppressive agents prior to TCZ. The method of initial TCZ administration was subcutaneous (162mg/ml) weekly in 48 (41%), subcutaneous every other week in 20 (17%), monthly 4mg/kg infusions in 34 (29%), monthly 8mg/kg infusions in 14 (12%) and non-standard dosing in 3 remaining patients. The median (IQR) duration from GCA diagnosis to TCZ initiation was 4.8 (1.2-22.0) months and the median (IQR) duration of TCZ treatment was 18 (11-28) months. The mean (SD) dose of prednisone at TCZ initiation was 31 (19) mg/day and was reduced to a mean (SD) dose of 3.9 (6.7) mg/day at TCZ discontinuation/last follow-up visit. The relapse rate per year decreased 43% from 0.77 to 0.44 after the initiation of TCZ (RR=0.57; 95% CI: 0.44-0.75; p<0.001). The mean (SD) ESR and CRP decreased from 22 (20) mm/hour to 6 (9.2) mm/hour and from 19.1 (25) mg/L to 5.4 (16.6) mg/L, respectively from TCZ initiation to TCZ discontinuation/last follow-up visit. At 2 years of follow-up, 67% of patients had discontinued glucocorticoids. At last follow up, 46 patients had discontinued TCZ, only 14 of which were due to adverse events. The median time to TCZ discontinuation was 2.9 years. Only 17% (95%CI: 10-24%) had discontinued by 1 year after TCZ initiation and 38% (95% CI: 26-47%) had discontinued by 2 years. The most common adverse events were infections and cytopenias. While on TCZ, 1 patient developed new onset vision loss related to GCA and 1 patient, without history of diverticulitis, had bowel perforation. Among those discontinuing TCZ, 61% had relapsed at least once by 1 year after TCZ discontinuation.Conclusion:In this large single institution cohort of patients with GCA, TCZ use resulted in a significantly reduced relapse rate and reduction in glucocorticoid dosage. Overall, patients tolerated long-term use with only 12% discontinuing due to adverse events. However, over half of patients stopping TCZ had a subsequent flare; highlighting ongoing use may be required beyond two years in several patients with GCA to maintain remission.References:[1]Stone JH, et al. Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med. 2017 Jul 27;377(4):317-328. doi: 10.1056/NEJMoa1613849. PMID: 28745999.[2]Calderón-Goercke M, et al. Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice. Semin Arthritis Rheum. 2019 Aug;49(1):126-135. doi: 10.1016/j.semarthrit.2019.01.003. Epub 2019 Jan 5. PMID: 30655091.Disclosure of Interests:Jigisha Rakholiya: None declared, Matthew Koster: None declared, Hannah Langenfeld: None declared, Cynthia S. Crowson: None declared, Andy Abril: None declared, Pankaj Bansal: None declared, Lester Mertz: None declared, Alicia Rodriguez-Pla: None declared, Rahul Sehgal: None declared, Benjamin Wang: None declared, Kenneth J Warrington Grant/research support from: Research support: Kiniksa, Eli Lilly


2016 ◽  
Vol 37 (3) ◽  
pp. 154-165 ◽  
Author(s):  
B. Bienvenu ◽  
K.H. Ly ◽  
M. Lambert ◽  
C. Agard ◽  
M. André ◽  
...  

Author(s):  
Jean-Charles Lafarge ◽  
Denis-Jean David ◽  
Cédric Carbonneil

IntroductionOne anastomosis gastric bypass (OAGB) has become a widespread technique over the last few years in France, without any prior assessment and despite existing controversies among bariatric surgeons. An older bypass technique for treating obesity, the Roux-en-Y gastric bypass (RYGB), is available and reimbursed, having been assessed and approved for use in 2005. In 2019, the French Haute Autorité de Santé (HAS) assessed OAGB for the treatment of severe and massive obesity. This assessment, the first in the world, was undertaken for OAGBs carried out with a 200- or 150-centimeter biliopancreatic-limb (BP-limb) length.MethodsA systematic review (SR) of the literature and consultation of a working group consisting of both healthcare professionals (clinician and surgeons) and patients were carried out. The primary aim of our assessment was to determine whether the OAGB technique can replace RYGB. The efficacy and safety profile of OAGB was compared with RYGB in adult patients with massive, severe obesity. Complications and postoperative follow up specific to OAGB were identified.ResultsThe three selected randomized controlled trials (RCTs) could not confirm the superiority or the non-inferiority of OAGB, compared with RYGB, on the selected efficacy endpoints of weight loss, resolution of comorbidities, and quality of life. Adverse events reported for OAGB included severe nutritional complications and bile reflux that could potentially lead to lower esophageal cancer. In one RCT, the frequency of serious adverse events in the OAGB group was almost two times higher than in the RYGB group.ConclusionsHAS considered that OAGB carried out with a longer (200 centimeter) BP-limb is not a validated technique for the surgical treatment of massive, severe obesity. Thus, it cannot be considered an alternative to RYGB. There were insufficient data available on OAGB performed with a 150-centimeter BP-limb. Thus, HAS recommended undertaking a multicenter RCT to assess the efficacy and safety of OAGB. Patients who have already undergone OAGB should receive the same follow up as patients who have received RYGB, including close monitoring for nutritional complications and lower esophageal cancer and an endoscopic examination five years after surgery.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 689.1-690
Author(s):  
S. Monti ◽  
L. Dagna ◽  
C. Campochiaro ◽  
A. Tomelleri ◽  
G. Zanframundo ◽  
...  

Background:Giant cell arteritis (GCA) is the most frequent systemic vasculitis after the age of 50 years old. Recent interest in the processes of immune and vascular aging have been proposed as a disease risk factor. Data on the impact of age at diagnosis of GCA on the clinical course of the disease are scarceObjectives:To assess the role of age at diagnosis of GCA on the risk and time to relapseMethods:Centres participating in the Italian Society of Rheumatology Vasculitis Study Group retrospectively enrolled patients with a diagnosis of GCA until December 2019. The cohort was divided in tertiles according to age at diagnosis (≤ 72; 73-79; > 79 years old). Negative binomial regression was used to assess the relapse rate according to age groups, and Cox regression for time to first relapse.Results:Of 720 patients enrolled in 14 Italian reference centres, 711 had complete follow-up data (female 50%; mean age 75±7). Median follow-up duration was 34 months (IQR 16;70). Patients in the older group at diagnosis (> 79 years) had more frequent visual loss compared to the 73-79 and ≤ 72 age groups (31% vs 20% vs 7%; p<0.001), but lower rates of general symptoms (56% vs 70% vs 77%; p<0.001). Large-vessel (LV)-GCA was less frequent in the older group (18% vs 22% vs 43%; p<0.001). At least one relapse occurred in 47% of patients. Median time to relapse was 12 months (IQR 6;23). Age did not influence the rate of relapses [18 per 100 persons/years (95%CI 15;21) vs 19 (95% CI 17;22) vs 19 (95%CI 17;22)], nor the time to first relapse (Figure 1). LV-GCA, presentation with significantly elevated c-reactive protein (> 50 mg/L) and general symptoms were independent predictors of relapse.Conclusion:Age at diagnosis of GCA influenced the clinical presentation and risk of ischaemic complications, but did not affect the relapse rate during follow-up. LV-GCA occurred more frequently in younger patients and was an independent predictor of relapse risk, highlighting the need for a correct characterization of the clinical subtype at the early stages of disease.Disclosure of Interests:Sara Monti: None declared, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Alessandro Tomelleri: None declared, Giovanni Zanframundo: None declared, Catherine Klersy: None declared, Francesco Muratore: None declared, Luigi Boiardi: None declared, Roberto Padoan: None declared, Mara Felicetti: None declared, Franco Schiavon: None declared, Milena Bond: None declared, Alvise Berti: None declared, Roberto Bortolotti: None declared, Carlotta Nannini: None declared, Fabrizio Cantini: None declared, Alessandro Giollo: None declared, Edoardo Conticini: None declared, angelica gattamelata: None declared, Roberta Priori: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Elena Treppo: None declared, Giacomo Emmi: None declared, Martina Finocchi: None declared, Giulia Cassone: None declared, Ariela Hoxha Speakers bureau: Celgene, UCB, Novartis, Sanofi, Werfen, Rosario Foti Consultant of: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Speakers bureau: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Michele Colaci: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Carlo Salvarani: None declared, Carlomaurizio Montecucco: None declared


Author(s):  
Fateh Bazerbachi ◽  
Akira Dobashi ◽  
Swarup Kumar ◽  
Sanjay Misra ◽  
Navtej S Buttar ◽  
...  

Abstract Background Endoscopic cyanoacrylate (glue) injection of fundal varices may result in life-threatening embolic adverse events through spontaneous gastrorenal shunts (GRSs). Balloon-occluded retrograde transvenous occlusion (BRTOcc) of GRSs during cyanoacrylate injection may prevent serious systemic glue embolization through the shunt. This study aimed to evaluate the efficacy and safety of a combined endoscopic–interventional radiologic (BRTOcc) approach for the treatment of bleeding fundal varices. Methods We retrospectively analysed the data of patients who underwent the combined procedure for acutely bleeding fundal varices between January 2010 and April 2018. Data were extracted for patient demographics, clinical and endoscopic findings, technical details, and adverse events of the endoscopic–BRTOcc approach and patient outcomes. Results We identified 30 patients (13 [43.3%] women; median age 58 [range, 25–92] years) with gastroesophageal varices type 2 (53.3%, 16/30) and isolated gastric varices type 1 (46.7%, 14/30) per Sarin classification, and median clinical and endoscopic follow-up of 151 (range, 4–2,513) days and 98 (range, 3–2,373) days, respectively. The median volume of octyl-cyanoacrylate: Lipiodol injected was 7 (range, 4–22) mL. Procedure-related adverse events occurred in three (10.0%) patients, including transient fever, non-life-threatening pulmonary glue embolism, and an injection-site ulcer bleed. Complete gastric variceal obturation was achieved in 18 of 21 patients (85.7%) at endoscopic follow-up. Delayed variceal rebleeding was confirmed in one patient (3.3%) and suspected in two patients (6.7%). Although no procedure-related deaths occurred, the overall mortality rate was 46.7%, primarily from liver-disease progression and co-morbidities. Conclusion The combined endoscopic–BRTOcc procedure is a relatively safe and effective technique for bleeding fundal varices, with a high rate of variceal obturation and a low rate of serious adverse events.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Owen Cronin ◽  
Neil D McKay ◽  
Hannah Preston ◽  
Helen Harris ◽  
Barbara Hauser

Abstract Background/Aims  Giant cell arteritis with large vessel vasculitis (LV-GCA) represents a distinct, less researched sub-category of giant cell arteritis (GCA). In comparison to cranial GCA, the patient’s diagnostic pathway is less well described and it is thought that LV-GCA is underdiagnosed, including in patients with polymyalgia rheumatica and cranial-GCA. Advances in imaging (e.g. PET-CT) and treatment (tocilizumab), have provided additional options in the diagnosis and management of LV-GCA. The aim was to describe the contemporary clinical journey for patients diagnosed with LV-GCA. Methods  The electronic patient health record system in NHS Lothian (TrakCare) was used to collect relevant data. Patients with imaging-confirmed large vessel vasculitis, diagnosed with GCA after 1 January 2017 were included. Follow-up was until August 2020. Results  Eighteen patients with LV-GCA were included. The mean age was 65 years and 66.7% were female. Two patients had known cranial-GCA but 89% of patients were diagnosed exclusively with large vessel involvement. The most common symptoms were malaise (55%), weight loss (55%), polymyalgia rheumatica (55%) and limb claudication (44%). Pyrexia of unknown origin was a feature in only 17% of patients. Two patients were asymptomatic and were investigated on the basis of raised inflammatory markers. Mean CRP at baseline was 99mg/L and ESR 85mm/hour. The mean time from symptom-onset to diagnosis was 6.8 months (range 1 to 15 months). Sixteen patients (89%) were reviewed by at least one other secondary care specialist. One third of patients were referred from General Medicine followed by Vascular Surgery (16%) and General Practice (16%). 7/18 patients were inpatients at the time of referral. 56% of patients required two modalities of imaging to confirm large vessel involvement. The most commonly used imaging techniques (in descending order) were CT-Chest/Abdomen/Pelvis, CT-angiogram, PET-CT and Vascular Ultrasound. 50% of patients underwent follow-up imaging, most commonly MR- or CT-angiography. Mean follow-up was for 1.6 years. The mean prednisolone dose at 3 months (n = 18) was 24mg daily and 8mg at 12 months (n = 12). 28% of patients relapsed during the follow-up period at 4, 5, 8, 9 and 24 months post-diagnosis. 7/18 patients were commenced on methotrexate for steroid-side effects or for relapse. 8/18 received subcutaneous tocilizumab in combination with methotrexate in two cases. Three patients were started on azathioprine but only one continued. Conclusion  In modern-day clinical practice, patients with LV-GCA experience a longer time to diagnosis than those with cranial symptoms. Patients with LV-GCA can experience an array of constitutional symptoms. Frequently, more than one imaging modality is required to confirm LV-GCA and the majority of patients will have seen other hospital specialists or have been admitted to hospital before diagnosis. Methotrexate and tocilizumab are the most frequently-used and effective steroid-adjunct in this single-centre cohort. Disclosure  O. Cronin: None. N.D. McKay: Consultancies; Gilead. Other; Has received support for conference attendance from Pfizer and Gilead, Has received educational support from UCB, Gilead, Celgene, Biogen, Sanofi, Abbvie, Novartis, Pfizer. H. Preston: None. H. Harris: None. B. Hauser: None.


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