Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial.

Importance: Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica. Objective: To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day. Interventions: Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone. Main Outcomes and Measures: The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone. Results: Of the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P < .001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 [95% CI, 5.4-9.6] vs 14.9 [95% CI, 11.4-18.4]; adjusted difference, -7.5 [95% CI, -11.2 to -3.8]; P < .001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% [95% CI, 18.9%-39.7%]; adjusted relative risk, 2.5 [95% CI, 1.8-3.5]; P < .001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group. Conclusions and Relevance: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms. Trial Registration: ClinicalTrials.gov Identifier: NCT02908217.

Systematic duplex ultrasound screening in conventional units for COVID-19 patients with follow-up of 5 days.

OBJECTIVE: COVID-19 patients may develop coagulopathy, which is associated with poor prognosis and high risk of thrombosis. The main objective of this work was to evaluate the prevalence of deep venous thrombosis of lower limbs (DVT) through ultrasonography in patients infected with COVID-19 admitted to conventional units at our hospital with 5 days of monitoring. The secondary objective was to determine if D-dimer levels, body mass index, and C-reactive protein were associated with DVT. METHODS: A total of 72 patients, with a mean age of 65 ± 12.3 years, infected with COVID-19 were admitted to three conventional units at our institution; 28 patients were women. A COVID-19 diagnosis was made by a transcriptase polymerase chain reaction by means of nasopharyngeal swab or by chest computer tomography without iodine contrast media. Demographics, comorbidities, and laboratory parameters were collected. A preventive anticoagulation treatment was established on admission with low-molecular-weight heparin. A complete venous duplex ultrasound (DU) test of lower limbs was performed on day (D) 0 and D5. A pulmonary computer tomography angiogram with iodine contrast media was required when pulmonary embolism was suspected. RESULTS: On D0, the DU showed acute DVT in seven patients (9.75%). A pulmonary computer tomography angiogram was performed in 12 patients (16.65%), 3 (25%) of whom had an acute pulmonary embolism. On D0, acute DVT was not significantly associated with C-reactive protein (mean 101 ± 98.6 in the group without DVT vs 67.6 ± 58.4 mg/L, P = .43) or body mass index (27.7 ± 5.04 vs 28.1 ± 2.65 kg/m2, P = .54). However, we found a significant association between acute DVT and D-dimer levels (1536 ± 2347 vs 9652 ± 10,205 ng/mL, P < .01). Among the patients included on D0, only 32 had a DU on D5. Forty of them (55.55%) were not examined for the following reasons: 7 (9.7%) were previously diagnosed with venous thromboembolism on D0 and therefore were excluded on D5, 8 (11%) were transferred to the intensive care unit, 10 (14%) were discharged from the hospital, 5 (7%) died, and 10 (13.9%) were excluded because of technical issues. On D5, five (15.6%) patients had acute DVT in addition to those found on D0; three were distal and two proximal despite preventive anticoagulation with low-molecular-weight heparin. CONCLUSIONS: Hospitalized non-intensive care unit patients with COVID-19 pneumonia have a high frequency of venous thrombotic events justifying screening with DU.