Background The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. Methods We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. Results We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P=0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P=0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P=0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. Conclusions Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937 .)

Opioid usage was more likely to be associated with subjective measures (depression, BASDAI, BASFI) than objective measures (CRP, ESR), suggesting that pain in AS may derive from sources other than spinal inflammation alone.

ObjectivesTo investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).MethodsDemographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression.ResultsOf 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25–2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39–2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42–0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19.ConclusionOlder age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

No abstract

Background:Spinal involvement in calcium pyrophosphate deposition disease (CPPD) is thought to be a rare occurrence and is seen infrequently as crowned dens syndrome. Furthermore, data on anatomical locations and correlates of calcium pyrophosphate (CPP) deposits in spinal CPPD are scarce.Objectives:To describe the anatomical locations and correlates of pathologically confirmed CPPD of the spine.Methods:Consecutive patients with spinal CPPD were identified via retrospective chart review of individuals who underwent spine surgery for intractable chronic neck or back pain at Massachusetts General Hospital between 2009 and 2014. These deposits and surrounding anatomical structures were surgically resected and confirmed to have calcium pyrophosphate deposition upon pathologic review. We reviewed musculoskeletal imaging (CT, MRI, XR) and laboratory data from these pathologically confirmed cases.Results:From April 2009 to August 2014, we identified 77 individuals with pathologically confirmed CPPD of the spine. The mean age was 68 years; 41 (53%) were female; mean BMI was 28.7. Calcium pyrophosphate (CPP) was grossly identified intraoperatively by the surgeon in 38 cases (50%), typically as “chalky white deposits” (Figure 1). CPP deposits were seen most frequently in the ligamentum flavum (23%) and intervertebral disc (23%), followed by other less common locations (Table 1). Imaging findings in the soft tissue or intervertebral disc suggestive of CPPD were found in 5 cases (6%), whereas findings of spinal canal narrowing, facet arthropathy, or ligamentum flavum thickening were eventually correlative with CPP deposits in pathologic specimens. Only 7 (9%) experienced a prior episode of acute CPP arthritis (pseudogout). Chondrocalcinosis on x-ray was seen in 26 cases (34%), most commonly in the wrist and/or knees. Osteoarthritis was present in all spinal imaging, and 65% had comorbid scoliosis. Laboratory abnormalities associated with secondary causes of CPPD (hypercalcemia, hypomagnesemia, hyperparathyroidism) were not seen with spinal CPPD.Conclusion:Spinal CPPD may occur more frequently than previously perceived. The ligamentum flavum and intervertebral discs were common anatomical locations for spinal CPPD. Advanced imaging of the spine showed low sensitivity for detecting spinal CPPD. Only a small minority had typical peripheral joint involvement or imaging with peripheral joint chondrocalcinosis. Thus, without pathologic confirmation, the vast majority of cases would remain unidentified. These findings call for the need to seek pathologic confirmation to determine the robust epidemiology and also raise the potential role for preoperative CPPD treatment.Table 1.Spinal Anatomic Locations of Pathologically Confirmed CPPDSpinal Anatomic LocationNo. of Sites (%)*ligamentum flavum29 (23)Intervetebral Disc28 (23)Other Location19 (15)Posterior Elements18 (15)Facet14 (11)Synovium8 (6)Interspinous Ligament3 (2)Subarticular/Lateral Recess2 (2)Fibrocartilaginous Tissue1 (1)Inner Spine1 (1)Other Ligament1 (1)*Some patients had more than one anatomic location where CPP was isolatedFigure 1.Gross visualization of calcium pyrophosphate deposition (black arrow)Disclosure of Interests:Jonathan Dau: None declared, Gary Ho: None declared, Hyon Choi Consultant of: Ironwood, Selecta, Horizon, Takeda, Kowa, Vaxart, Grant/research support from: Ironwood, Horizon, Joseph Schwab: None declared, Minna Kohler Speakers bureau: Eli Lily, Consultant of: Novartis.

No abstract

No abstract

BackgroundPatients with ankylosing spondylitis (AS) are at higher risk for developing cardiovascular comorbidities. While aortic valve and conduction defects are most common, increased levels of LDL cholesterol are also seen. Statin usage has been reported to lower CRP and ESR though the power of these studies are limited due to small sample size and short-term follow-up (1,2).ObjectivesThis study examines associations of statin usage with socio-demographic and clinical factors, including disease activity, functional impairment, and radiographic severity in patients with two years of follow-up or more.Methods655 AS patients meeting modified New York criteria followed at least 2 years (and up to 12 years) were included in the analysis. Demographic and clinical parameters (disease activity and functional impairment were collected every 6 months, as well as radiographic assessments (BASRI and mSASSS) every 2 years. Univariable and multivariable mixed effect models were developed to identify independent factors associated with statin usage over time.ResultsMean disease duration was 18 years (SD=13). 10% (n=66) of the cohort were using statins. Univariable longitudinal regression models are shown below:Factors associated with statin usage based on a univariable longitudinal analysisVariableOR95% CIP-valueMale gender2.7(1.4,5.4)0.004White3.8(1.7,8.6)0.001Marital status: married3.3(1.9, 6.0)<0.001Disease duration >20 years15.8(8.6, 28.7)<0.001Age >40 years5.5(2.3,13.3)<0.001History of hip involvement0.4(0.3, 0.8)0.004History of cardiovascular comorbidity13.7(7.7,24.4)<0.001History of diabetes4.7(1.4,15.4)0.01History of smoking2.2(1.2,3.8)0.01History of hypertension9.9(5.4,17.4)<0.001Concomitant use of NSAID's0.4(0.2,0.8)0.01Concomitant use of TNF-blockers1.0(0.6,1.5)0.96Radiographic severity (mSASSS >4)3.8(2.1,6.7)<0.001Radiographic severity (BASRI >6)2.6(1.6,4.4)0.001Impaired functionality (BASFI >4)1.6(1.1,2.5)0.03Disease activity (BASDAI >4)0.6(0.3,0.9)0.04Elevated CRP0.7(0.5,0.9)0.03Elevated ESR1.1(0.7,1.5)0.76Multivariable longitudinal analyses controlling for confounders showed independent associations of age >40 years (p<0.001, OR=5.5 (2.3, 13.3)), the presence of cardiovascular disease (p<0.001, OR=7.6 (3.8, 15.5)), diabetes (p=0.01, OR=4.7 (1.4, 15.4)), opiate use (p=0.03, OR=2.0 (1.1, 3.7)), and CRP (p=0.03, OR=0.4 (0.2, 0.9)).ConclusionsStatin usage was, as expected, more likely in those of older age with greater disease duration and greater radiographic severity. Even though statins are known to reduce CRP, the association with markers of lower disease activity, both subjective (BASDAI on univariable analysis) and objective (CRP on both univariable and multivariable analyses), raises the possibility of a role in suppressing inflammation in patients with AS.ReferencesHeinemann S and Daemen M. Cardiovascular risks in spondyloarthropaties. Curt Opin Rheumatol. 2007 19:358–362.Denderen JC, Peters MJL, van Halm VP, van de Horst-Bruinsma, Dijkmans BAC, Nurmohamed MT. Statin therapy might be beneficial for patients ...