Search

Background:Visual involvement is one of the most feared complication of Giant Cell Arteritis (GCA).Tocilizumab (TCZ) has shown efficacy and safety in large-vessel vasculitis (LVV) including GCA (1-4).Objectives:To assess the efficacy of TCZ to: a) prevent the appearance of new ocular involvement, and b) to improve visual symptoms if present.Methods:Observational, multicenter study of 312 patients with GCA treated with TCZ. Patients were diagnosed with GCA accordingly to a) ACR criteria, and/or b) biopsy of temporal artery, and/or c) presence of LVV by imaging.Patients were divided into two subgroups: a) with, and b) without visual involvement at any time. Visual manifestations were classified as: a) Transient visual loss (TVL) (amaurosis fugax), b) Permanent visual loss (PVL) (longer than 24 hours) (partial or complete; unilateral or bilateral), c) diplopia, and d) blurred vision. Accordingly to visual duration up to TCZ onset, we considered: a) 1-10 days, b) 11-30 days, and c) more than 30 days.Results:We studied 312 (218 women/94 men; mean age73.4±9.6 years). Visual manifestations at any time (before and/or after TCZ) were observed in 78 (25%). In 47 of them visual manifestations were present at TCZ onset, and in the remaining 31 patients had had a complete recovery. Main clinical features of GCA with and without visual involvement are shown in TABLE. Patients with visual involvement were older, with other ischemic complications, and requiring more corticosteroids dose.Table 1.Main features of 312 patients at TCZ onset.OverallN= 312GCA with visual involvement(n= 78)GCA without visual involvement(n=234)pGeneral featuresAge (mean±SD)73.4±9.676.6±8.072.4±9.80.001*Female/Male(% of female), n218/94 (70)47/31 (60)171/63(73)0.046*Time from GCA diagnosis to TCZ onset (months), median [IQR]8 [3-24]5 [1-14]10 [3-24]0.040*Positive TAB, n (%)137/229 (60)33/60 (55)104/169 (61)0.444Ischemic manifestationsVisual involvement, n (%)47 (15)47 (60)00.000*Headache, n (%)166 (53)59 (76)107 (46)0.000*Jaw claudication60 (19)26 (33)34 (14)0.001*Systemic manifestationsFever, n (%)27 (9)8 (10)19 (8)0.743Constitutional syndrome, n (%)115 (37)30 (38)85 (36)0.878PmR, n (%)188 (60)46 (59)142 (61)0.830Acute phase reactantsESR, mm/1st hour, median [IQR]27 [10-50]34.5 [15.2-58]26.0 [10.0-48.0]0.193CRP (mg/dL), median [IQR]1.4 [0.4-3.3]1.5 [0.3-5.5]1.3 [0.4-2.9]0.134Prednisone dose, mg/day, mean±SD22.3±16.627.1±18.620.8±15.60.008*TCZmono/TCZcombo, n (%)211/10157/21154/800.295Follow-up (months), mean±SD28.4±21.825.8±22.429.3±21.60.119After TCZ onset, none patient developed new visual involvement. At TCZ onset 47 patients had the following visual manifestations; PVL (n= 28; unilateral/bilateral; 22/6), TVL (n=15; unilateral/bilateral; 9/6), diplopia (n=2) and blurred vision (n=2).None of the patients with TVL presented new episodes after TCZ onset, while 8 out of 28 patients with PVL experienced partial improvement (FIGURE). The 2 patients with diplopia and 1 of 2 patients with blurred vision improved.Figure 1.Efficacy of TCZ in 47 patients with GCA and visual involvement at TCZ onset.Conclusion:TCZ seems to prevent the appearance of new ocular manifestations. When they are present, TCZ may improve totally TVL and partially PVL.References:[1]Stone JH, et al. N Engl J Med. 2017; 377: 317-28.[2]Calderón-Goercke M, et al. Semin Arthritis Rheum 2019;49:126-35. https://doi.org/10.1016/j.semarthrit.2019.01.003.[3]Prieto Peña D et al. Clin Exp Rheumatol 2020 Nov 27. PMID: 33253103.[4]Loricera J, et al. Clin Exp Rheumatol 2016; 34:S44-53. PMID: 27050507.Disclosure of Interests:Lara Sanchez-Bilbao: None declared, Javier Loricera: None declared, Vicente Aldasoro: None declared, Rafael Melero: None declared, Santos Castañeda: None declared, Olga Maiz: None declared, Clara Moriano: None declared, Ignacio Villa-Blanco: None declared, Eztizen Labrador-Sánchez: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, Eva Galíndez-Agirregoikoa: None declared, Eva Perez-Pampín: None declared, Andrea García-Valle: None declared, Cristina Campos Fernández: None declared, Juan Ramón De Dios: None declared, Carlota Laura Iñíguez: None declared, José Luis Andréu Sánchez: None declared, Julio Sánchez: None declared, Monica Calderón-Goercke: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Consultant of: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: Abbvie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Consultant of: Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Grant/research support from: Abbvie, MSD and Roche

Background:Giant cell arteritis (GCA) may be divided into cranial, and extracranial GCA. Tocilizumab (TCZ) has shown efficacy and safety in GCA and other large-vessel vasculitis (LVV) (1-5).Objectives:To compare the efficacy of TCZ in cranial and extracranial GCA.Methods:Multicenter observational study of 312 patients with GCA treated with TCZ. They were divided into 3 groups a) only cranial (cGCA), b) only extracranial (ecGCA), c) mixed affection (mixGCA). GCA was diagnosed by a) ACR criteria, and/or b) positive temporal artery biopsy, and/or c) LVV by imaging. Remission and sustained remission was defined according to EULAR definitions (1). In ecGCA and mixGCA we also studied the improvement (complete or partial) by imaging techniques.Results:We studied 312 patients (218 females; mean age, 73.4±9.6 years). TABLE shows the main features of the 3 groups. Remission at month 6 was higher in cGCA, as well as the sustained remission at month12 (FIGURE). At 18 and 24months, were similar in the 3 groups. Improvement by imaging techniques was partial/complete at 6,12,18 and 24 months, in 50%/0%,71%/0%, 61%/15% and 67%/17% respectively, in ecGCA, and in 75%/0%,53%/18%, 64%/12% and 50%/28% in mixGCA.Table 1.Main features of 312 patients at TCZ onset.Cranial GCA(n=152)Extracranial GCA(n=49)Mixed GCA(n=111)Cranial vs Extracranial GCApAge at TCZ onset, years, mean± SD76.0±8.265.4±12.273.5±8.10.000*Sex, female/male, n (% female)105/47 (69)33/16 (67)80/31 (72)0.960Time from diagnosis to TCZ onset (months, median [IQR]6 [2-21]7 [2-20]9 [3-25]0.765Biopsy-proven GCA, n (%)87/128 (68)0 (0)50/87 (57)0.000*Systemic manifestations at TCZ onset109 (72)32 (65)84 (76)0.501Fever, n (%)18 (12)1 (2)8 (7)0.048*Constitutional syndrome, n (%)52 (34)16 (33)47 (42)0.933PmR, n (%)88 (58)29 (59)71 (64)0.999Ischemic manifestations at TCZ onset117 (77)0 (0)70 (63)0.000*Visual involvement, n (%)31 (20)0 (0)16 (14)0.000*Headache, n (%)103 (85)0 (0)63 (57)0.000*Jaw claudication, n (%)39 (26)0 (0)21 (19)0.000*Acute phase reactantsESR, mm/1st hour, median [IQR]28 [9-53]24 [10-43]28 [15-48]0.462CRP, mg/dL, median [IQR]1.2 [0.3-3.4]0.7 [0.4-1.8]1.6 [0.4-3.8]0.153Prednisone dose at TCZ onset, mean ± SD26.2±17.615.4±14.220.1±14.90.000*TCZmono/TCZcombo, n (% TCZ mono)116/36 (76)26/23 (53)69/42 (62)0.003*Follow-up (months), mean ± SD27.3±21.132.7±23.327.9±22.00.143Figure 1.Remission and sustained remission of cGCA, ecGCA and mixGCA according to EULAR (1). In the first 3 months we only could assess cGCA because in ecGCA and mixGCA a control imaging was not performedConclusion:TCZ seems to be effective in all phenotypes but it is faster in cGCA in reaching remission. However, improvement by imaging techniques was partial and very rarely complete in ecGCA and mixGCA.References:[1]Hellmich B, et al. Ann Rheum Dis. 2020; 79: 19-30.[2]Stone JH, et al. N Engl J Med. 2017; 377: 317-28.[3]Calderón-Goercke M, et al. Semin Arthritis Rheum 2019; 49:126-35. https://doi.org/10.1016/j.semarthrit.2019.01.003.[4]Prieto Peña D et al. Clin Exp Rheumatol 2020 Nov 27. PMID: 33253103.[5]Loricera J, et al. Clin Exp Rheumatol 2016; 34:S44-53. PMID: 27050507Disclosure of Interests:Lara Sanchez-Bilbao: None declared, Javier Loricera: None declared, Vicente Aldasoro: None declared, Juan Pablo Valdivieso-Achá: None declared, Ignacio Villa-Blanco: None declared, Olga Maiz: None declared, Rafael Melero: None declared, Clara Moriano: None declared, Julio Sánchez: None declared, Eugenio de Miguel: None declared, Eva Perez-Pampín: None declared, Juan Ramón De Dios: None declared, Juan Carlos Nieto González: None declared, Eva Galíndez-Agirregoikoa: None declared, Patricia Moya: None declared, Francisca Sivera: None declared, José Luis Andréu Sánchez: None declared, Valvanera Pinillos: None declared, Andrea García-Valle: None declared, Paloma Vela-Casasempere: None declared, Noelia Alvarez-Rivas: None declared, Marcelino Revenga: None declared, Sara Manrique Arija: None declared, Carlos Fernández-López: None declared, Enrique Raya: None declared, Cristina Hidalgo: None declared, Ruth López-González: None declared, Cristina Campos Fernández: None declared, Antonio Juan-Mas: None declared, Beatriz Arca: None declared, Iñigo Rua-Figueroa: None declared, María Dolors Boquet: None declared, Antonio García: None declared, Adela Gallego: None declared, Eva Salgado-Pérez: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Grant/research support from: Abbvie, MSD, Jansen and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Grant/research support from: Abbvie, MSD and Roche

Background:Infections are the most common adverse event of Tocilizumab (TCZ) in Giant Cell Arteritis (GCA). In GiACTA study(1),serious infections were observed in 7% (9.6/100 patient-years) of patients who received TCZ weekly. Randomized clinical trials (RCTs) are conducted under highly standardized design excluding some real-world patients. Therefore, adverse events may be underestimated in RCTs. In our series of real-life, serious infections occurred in 11.9% (10.6/100 patient-years)(2).Objectives:In a wide series of GCA of clinical practice treated with TCZ, we assess the frequency, type and predisposing factors of serious infections.Methods:Multicenter study of 134 patients diagnosed with GCA, all of them refractory to conventional therapy, treated with TCZ. Serious infection was considered when a life-threatening infection, fatal, or requiring hospitalization occurred, intravenous antibiotics were required, or the infectious process led to persistent or significant disability.Results:16 of 134 (11.9%, 10.6/100 patient-years) patients developed serious infections during follow-up. The most frequent infections were pneumonia (n=4), urinary tract infection (n=4), and facial herpes zoster (n=2). At TCZ onset, serious infections were more frequent in older patients (74.3±9.6 vs 72.9±8.7 years), with a longer GCA evolution (20 [4.3-45.6] vs 13 [5-29.3] months), with visual manifestations (43.75% vs 17.8%) and a higher dose of prednisone at TCZ onset (30.4±15.5 vs 21.1±16.1 mg/day) (TABLE). Presence of comorbidities were similar in both groups. 13 of the 16 patients who had infections received a dose of prednisone greater than 15 mg/day (16.3/100 patient-years) compared to 3 patients under treatment with less than 15 mg/day of prednisone (4.2/100 patient-years).Conclusion:The age, GCA duration, ocular involvement and the dose of glucocorticoids, at TCZ onset, seem to be predisposing factors related to an increased risk of developing serious infections in GCA patients.References:[1]Stone JH, et al. N Engl J Med. 2017; 377:317-28.[2]Calderón-Goercke M et al. Semin Arthritis Rheum 2019 Aug;49(1): 126-135.TABLESERIOUS INFECTIONS(n=16)WITHOUT SERIOUS INFECTIONS(n=118)pBASAL FEATURES AT TCZ ONSETGENERAL FEATURES Age, years, mean± SD74.3±9.672.9±8.70.552 Sex, female/male n(%)13/388/300.760 Time from GCA diagnosis to TCZ onset (months), median [IQR]20[4.3-45.6]13[5-29.3]0.604COMORBIDITIES Hypertension, n(%)9(56)86(73)0.551 Diabetes, n(%)3(19)39(33)0.677 Chronic kidney disease, n(%)3(19)27(23)0.512CLINICAL FEATURES OF GCA PMR, n(%)9(56.25)64(54.2)0.879 Aortitis, n(%)5(31.25)53(45)0.301 Visual manifestations, n(%)7(43.75)21(17.8)0.017CORTICOSTEROIDS AT TCZ ONSET Prednisone dose mg/d, mean (SD)30.4±15.521.1±16.10.031Disclosure of Interests:Monica Calderón-Goercke: None declared, D. Prieto-Peña: None declared, Santos Castañeda: None declared, Clara Moriano: None declared, Elena Becerra-Fernández: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Águeda Prior-Español: None declared, E. Galindez: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Eva Salgado-Pérez: None declared, Vicente Aldasoro Speakers bureau: Roche, Abbvie, MSD, UCB, Pfizer, Menarini, Grunenthal, Gebro, Novartis, Janssen, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Susana Romero-Yuste: None declared, J. Narváez: None declared, Catalina Gomez-Arango: None declared, Eva Perez-Pampín: None declared, Rafael Melero: None declared, Francisca Sivera: None declared, Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Alejandro Olive: None declared, María Álvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernández-López: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Beatriz Arca: None declared, Roser Solans-Laqué: None declared, Arantxa Conesa: None declared, Carlos Vázquez: None declared, Jose Andrés Román-Ivorra: None declared, Pau Lluch: None declared, Paloma Vela-Casasempere: None declared, Carmen Torres-Martín: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Carmen Ordas-Calvo: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Sáenz de Miera: None declared, Nagore Fernández-Llanio: None declared, Antonio García: None declared, Carmen González-Vela: None declared, Javier García-Fernández: None declared, Patricia Vicente-Gómez: None declared, Ángel García-Manzanares: None declared, Norberto Ortego: None declared, Francisco Ortiz-Sanjuán: None declared, Montserrat Corteguera: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background:Tocilizumab (TCZ) is the only biological agent approved in Giant Cell Arteritis (GCA). There is general agreement on the initial and the standard maintenance dose of TCZ. However, information on duration and optimization of TCZ in GCA is scarce.Objectives:Our aim was to assess efficacy and safety of TCZ therapy optimization in an unselected wide series of GCA in clinical practice.Methods:Multicenter study, 134 patients with GCA who received TCZ due to inefficacy/adverse events of previous therapy. Once complete remission was reached and based on a shared decision between patient and physician TCZ was optimized in some cases. Optimization was done by decreasing the dose and/or prolonging the TCZ dosing interval progressively.Results:134 GCA patients treated with TCZ (101w/33m); mean age 73.0±8.8 years. TCZ was administered IV to 106 (79.1%) patients and SC to 28 (20.9%). TCZ was optimized in 43 (32.1%) patients. No demographic, clinical manifestations or laboratory data differences had been found at TCZ onset (TABLE). After a follow up of 12 [6-15.5] months, and a complete remission for 6 [3-12] months; the first TCZ optimization was performed. Median prednisone dose at first TCZ optimization was 2.5 [0-5] mg/day. TCZ IV was optimized from 8 to 4 mg/kg/4weeks in 12 of 106 (11.3%) and from 162 mg/SC/week to 162 mg/SC/2weeks in 9 of 28 (32.1%) cases. Five (11.6%) of the 43 optimized cases relapsed. In 4 cases, the relapses were treated increasing TCZ up to the pre-optimization dose, in 1 case the route of administration was change (4 mg/kg/4week to 162 mg/SC/week). In 8 of 43 optimized patients (18.6%), it was possible to withdraw TCZ after complete remission for 30 [16.25-45.75] months. Regarding adverse events and severe infections were similar in both groups. The mean TCZ treatment costs were lower in the optimized group.Conclusion:Once remission is reached in GCA patients under TCZ treatment, optimization of TCZ may be performed. Based on our experience it could be performed by reducing the dose with IV TCZ or by prolonging dosing interval with SC TCZ.References:[1]Calderón-Goercke M et al. Semin Arthritis Rheum 2019 Aug;49(1): 126-135.TABLE.OPTIMIZED-TCZ GROUP (n=43)NON-OPTIMIZED TCZ GROUP (n=91)pBASAL FEATURES AT TCZ ONSETGENERAL FEATURESAge, years, mean± SD68.9±8.771.4±8.50.125Sex, female/male n(%)32/1068/240.779Time from GCA diagnosis to TCZ onset (months), median [IQR]19.5[7.75-45]10.5[4 – 25]0.047SYSTEMIC MANIFESTATIONSFever, n(%)1(2.4)8(8.7)0.176Constitutional syndrome, n(%)11(26.2)19(20.7)0.476PMR, n(%)18(42.9)56(60.9)0.052ISCHEMIC MANIFESTATIONSVisual involvement, n(%)5(11.9)23(25)0.084Headache, n(%)26(61.9)42(45.7)0.081Jaw claudication, n(%)1(2.4)11(12)0.072CORTICOSTEROIDS AT TCZ ONSETPrednisone dose, mg/d mean (SD)15.1±11.125±17.40.001FOLLOW-UP ON TCZ THERAPY (MONTHS), MEDIAN [IQR]24[18-27]6 [3-18]0.000Relapses, n(%)5(11.6)5(5.5)0.207End follow-up remission, n(%)40(93)84(92)0.99Severe side efects, n(%)14(32.6)22(24.2)0.307Seriuos infections, n(%)6(14)10(11)0.878Cost, (mean) euros per yearIVSC7 538.47 329.011 726.411 726.4--Disclosure of Interests:Monica Calderón-Goercke: None declared, D. Prieto-Peña: None declared, Santos Castañeda: None declared, Clara Moriano: None declared, Elena Becerra-Fernández: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Águeda Prior-Español: None declared, E. Galindez: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Eva Salgado-Pérez: None declared, Vicente Aldasoro Speakers bureau: Roche, Abbvie, MSD, UCB, Pfizer, Menarini, Grunenthal, Gebro, Novartis, Janssen, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Susana Romero-Yuste: None declared, J. Narváez: None declared, Catalina Gomez-Arango: None declared, Eva Perez-Pampín: None declared, Rafael Melero: None declared, Francisca Sivera: None declared, Alejandro Olive: None declared, María Álvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernández-López: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Beatriz Arca: None declared, Roser Solans-Laqué: None declared, Arantxa Conesa: None declared, Carlos Vázquez: None declared, Jose Andrés Román-Ivorra: None declared, Pau Lluch: None declared, Paloma Vela-Casasempere: None declared, Carmen Torres-Martín: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Carmen Ordas-Calvo: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Sáenz de Miera: None declared, Nagore Fernández-Llanio: None declared, Antonio García: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD