Abstract: Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.

Abstract: 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. TABLE SERIOUS INFECTIONS (n=16 ) WITHOUT SERIOUS INFECTIONS (n=118 ) p BASAL FEATURES AT TCZ ONSET GENERAL FEATURES  Age, years, mean± SD 74.3±9.6 72.9±8.7 0.552  Sex, female/male n(%) 13/3 88/30 0.760  Time from GCA diagnosis to TCZ onset (months), median [IQR] 20[4.3-45.6] 13[5-29.3] 0.604 COMORBIDITIES  Hypertension, n(%) 9(56) 86(73) 0.551  Diabetes, n(%) 3(19) 39(33) 0.677  Chronic kidney disease, n(%) 3(19) 27(23) 0.512 CLINICAL 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) 0.017 CORTICOSTEROIDS AT TCZ ONSET  Prednisone dose mg/d, mean (SD) 30.4±15.5 21.1±16.1 0.031 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, 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

Abstract: 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 ) p BASAL FEATURES AT TCZ ONSET GENERAL FEATURES Age, years, mean± SD 68.9±8.7 71.4±8.5 0.125 Sex, female/male n(%) 32/10 68/24 0.779 Time from GCA diagnosis to TCZ onset (months), median [IQR] 19.5[7.75-45] 10.5[4 – 25] 0.047 SYSTEMIC MANIFESTATIONS Fever, n(%) 1(2.4) 8(8.7) 0.176 Constitutional syndrome, n(%) 11(26.2) 19(20.7) 0.476 PMR, n(%) 18(42.9) 56(60.9) 0.052 ISCHEMIC MANIFESTATIONS Visual involvement, n(%) 5(11.9) 23(25) 0.084 Headache, n(%) 26(61.9) 42(45.7) 0.081 Jaw claudication, n(%) 1(2.4) 11(12) 0.072 CORTICOSTEROIDS AT TCZ ONSET Prednisone dose, mg/d mean (SD) 15.1±11.1 25±17.4 0.001 FOLLOW-UP ON TCZ THERAPY (MONTHS), MEDIAN [IQR] 24[18-27] 6 [3-18] 0.000 Relapses, n(%) 5(11.6) 5(5.5) 0.207 End follow-up remission, n(%) 40(93) 84(92) 0.99 Severe side efects, n(%) 14(32.6) 22(24.2) 0.307 Seriuos infections, n(%) 6(14) 10(11) 0.878 Cost, (mean) euros per year IV SC 7 538.4 7 329.0 11 726.4 11 726.4 - - 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

Abstract: There are different measures and tools validated to evaluate disease activity and damage in idiopathic inflammatory myopathies (IIM). Disease activity and damage in patients with early diagnosis is not still well defined. Objectives To analyze disease activity outcomes and their association with damage in IIM differentiating between incident and prevalent cases. Methods Multicenter cross-sectional study of a cohort of patients included in the Spanish Registry of patients with IIM (Myo-Spain)(1). Patients were classified as incident cohort (time between diagnosis and study initiation ≤ 12 months) or prevalent cohort ( 〉 12 months). Activity and damage data were collected at the initial visit. Differences between both groups were tested by Chi-square, Student’s t and Mann-Whitney tests. Spearman’s correlation coefficients (Rho) were used to analyze correlations between disease activity and damage measures (weak ≥ 0.2 - 〈 0.3; moderate ≥ 0.3 〈 0.7; strong ≥ 0.7). Results We included 139 (67.63% women) and 417 patients (74.34% women) with a mean age at diagnosis of 54 and 48 years in the incident and prevalent cohort, respectively. Patients in the incident cohort had significantly higher disease activity measures: myositis disease activity assessment visual analogue scale (MYOACT) total, extramuscular activity of MYOACT, physician global activity (PhGA), patient global activity (PGA), manual muscle testing (MMT)8, CK, and HAQ (p 〈 0.001).The organ systems with the bigger differences between the incident and the prevalent cohort were skin and constitutional (p 〈 0.001). No significant differences were found respect to physician global damage (PhGD), patient global damage (PGD) and myositis damage index (MDI), between both cohorts (p 〉 0.2). Correlations between disease activity and damage measures are showed in the Table 1. The main differences found between both cohorts were the correlations of PhGA, CK, PGD and MDI with other measures of disease activity. Table 1. Correlations between disease activity and damage measures Incident cohort Prevalent cohort MYOACT total Extramuscular activity of MYOACT PhGA MMT- 8 MYOACT total Extramuscular activity of MYOACT PhGA MMT- 8 Extramuscular activity of MYOACT Rho 0.76 1 0.673 -0.166 0.777 1 0.764 -0.214 P-value 〈 0.001 〈 0.001 〈 0.001 0.065 〈 0.001 〈 0.001 〈 0.001 〈 0.001 PhGA Rho 0.823 0.673 1 -0.5 0.779 0.764 1 -0.301 P-value 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 PGA Rho 0.667 0.544 0.679 -0.434 0.585 0.528 0.623 -0.345 P-value 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 MMT-8 Rho -0.471 -0.166 -0.5 1 -0.383 -0.214 -0.301 1 P-value 〈 0.001 0.065 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 CK Rho 0.221 -0.086 0.234 -0.438 0.07 -0.024 0.112 -0.11 P-value 0.014 0.351 0.008 〈 0.001 0.178 0.648 0.029 0.034 HAQ Rho 0.486 0.338 0.528 -0.49 0.386 0.248 0.384 -0.505 P-value 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 PhGD Rho 0.367 0.31 0.448 -0.305 0.573 0.492 0.598 -0.334 P-value 〈 0.001 0.001 〈 0.001 0.001 〈 0.001 〈 0.001 〈 0.001 〈 0.001 PGD Rho 0.293 0.163 0.354 -0.295 0.468 0.408 0.476 -0.347 P-value 0.003 0.102 〈 0.001 0.002 〈 0.001 〈 0.001 〈 0.001 〈 0.001 MDI Rho 0.398 0.279 0.388 -0.232 0.579 0.477 0.545 -0.343 P-value 〈 0.001 0.006 〈 0.001 0.026 〈 0.001 〈 0.001 〈 0.001 〈 0.001 Myositis disease activity assessment visual analogue scale (MYOACT), physician global activity (PhGA), patient globalactivity (PGA), manual muscle testing (MMT)8, health assessment questionnaire (HAQ), physician global damage(PhGD), patient global damage (PGD), myositis damage index (MDI). Conclusion Incident cases had higher disease activity. In those in whom damage was detected, no differences were found in damage measures with prevalent cases. The correlation between the different measures of activity and damage was slightly better in prevalent patients. References [1]Cobo-Ibáñez T, et al. Myo-Spain: Spanish Registry of patients with idiopathic inflammatory myopathy. Methodology. Reumatol Clin (Engl Ed). 2021 Aug 13:S2173-5743(21)00156-8. Acknowledgements To Nuria Montero for her contribution to data monitoring, and Francisco Javier Prado-Galbarro for his contribution to data analysis. Disclosure of Interests None declared

Abstract: Tocilizumab (TCZ) has shown to be effective for large vessel vasculitis including giant cell arteritis (GCA) and Takayasu arteritis (TAK) (1-5 ). However, LVV-GCA and TAK show different demographic and clinical features that may influence on TCZ therapeutic response. Objectives To compare the effectiveness of TCZ in patients with LVV-GCA and patients with TAK. Methods Observational multicenter study of patients with LVV-GCA and TAK who received TCZ. Outcome variables were: a ) proportion of patients who achieved complete clinical improvement along with normalization of laboratory markers (CRP ≤0.5mg/dL and/or ESR ≤ 20 mm/1st hour) at 12 months b ) complete improvement in imaging techniques. A comparative study between patients with LVV-GCA and TAK was performed. Results We evaluated 70 LVV-GCA and 57 TAK patients who received TCZ. Main clinical and demographic characteristic are described in Table 1. Patients with TAK were younger, had longer disease duration, had received more commonly previous biologic therapy and were receiving higher doses of prednisone at baseline. TCZ intravenous administration was more common in TAK patients (80.7% vs 48.6%; p 〈 0.01). Follow-up time after TCZ onset was similar in both groups. At 12 months, about 75% of patients achieved complete clinical improvement and ESR/CRP normalization in both groups. A follow-up imaging technique was performed in 37 LVV-GCA patients after a mean time of 12.9±6.0 months and 38 TAK patients after 9.5±5.0 months. Complete improvement in imaging techniques was only observed in 18.9% and 21.1% of patients with LVV-GCA and TAK, respectively (Figure 1). Table 1. LVV-GCA (n=70) TAK (n=57) p General features Age (years), mean ± SD 67.2 ± 10.5 40.5 ± 16.3 〈 0.01 Sex (female), n (%) 51 (72.9) 49 (86) 0.07 Disease evolution before TCZ onset (months), median [IQR] 5 [2-15] 12 [3-37] 〈 0.01 Baseline laboratory parameters ESR (mm/1st hour), median [IQR] 32 [12.5-54.7] 31 [10-52] 0.82 CRP (mg/dL), median [IQR] 1.4 [0.5-2.4] 1.4 [0.5-3.5] 0.41 Baseline prednisone dose (mg/day), median [IQR] 15 [10-20] 30 [15-50] 〈 0.01 Previous therapy Conventional DMARDs, n(%) 45 (64.3) 44(77.2) 0.51 Biologic therapy, n (%) 0(0) 12 (21.1) 〈 0.01 TCZ therapy Intravenous, n (%) 34 (48.6) 46 (80.7) 〈 0.01 Combined with MTX, n(%) 24 (34.3) 24 (42.1) 0.37 Follow-up time after TCZ onset, median [IQR] 20 [10-36] 18 [7-41] 0.73 Complete clinical improvement and ESR/CRP normalization at 12 months, n/N (% ) 35/47 (74.4) 30/39 (76.9) 0.79 Complete improvement in imaging techniques, n/N(% ) 7/37 (18.9) 8/38 (21.1) 0.85 CRP: C-reactive protein; DMARDs: Disease-modifying anti-rheumatic drugs ESR: erythrocyte sedimentation rate; GCA: giant cell arteritis; IQR: interquartile range; LVV: large vessel; MTX: methotrexate; n: Number of patients; N: total number of patients: TCZ: tocilizumab; TAK:takayasu Figure 1. Conclusion The effectiveness of TCZ was similar in patients with LVV-GCA and TAK, despite a more refractory disease in TAK patients. A discordance between clinical and imaging activity improvement was observed in both LVV-GCA and TAK, as reported in previous studies (3 ). References [ 1 ] Calderón-Goercke M, et al. Semin Arthritis Rheum 2019; 49:126-35. https://doi.org/10.1016/j.semarthrit.2019.01.003 [2]Prieto-Peña D et al. Ther Adv Musculoskelet Dis. 2021;13:175. PMID: 34211589. [3]Prieto Peña D et al. Clin Exp Rheumatol. 2021;39 Suppl 129:69-75. PMID: 33253103. [4]González-Gay MA, et al. Expert Opin Biol Ther. 2019;19:65-72. doi: 10.1080/14712598.2019.1556256. [5]Prieto-Peña D, et al. Semin Arthritis Rheum. 2019;48(4):720-727. doi: 10.1016/j.semarthrit.2018.05.007 Disclosure of Interests None declared