In patients with active rheumatoid arthritis despite methotrexate treatment, a single course of two infusions of rituximab, alone or in combination with either cyclophosphamide or continued methotrexate, provided significant improvement in disease symptoms at both weeks 24 and 48.

Although "optimum" conditions were present in the patients receiving beta-blocker, the authors thought that the grading system was not discriminating enough to demonstrate a significant difference between the groups. The crucial finding in the study was the correlation between heart rate and surgical grade in the entire group. During endoscopic sinus surgery surgery, anesthetic manipulations should be directed at maintaining a low heart rate.

Objective. To investigate the efficacy and safety of ocrelizumab in patients with class III/IV lupus nephritis (LN).Methods. Patients were randomized 1:1:1 to receive placebo, 400 mg ocrelizumab, or 1,000 mg ocrelizumab given as an intravenous infusion on days 1 and 15, followed by a single infusion at week 16 and every 16 weeks thereafter, accompanied by background glucocorticoids plus either mycophenolate mofetil (MMF) or the Euro-Lupus Nephritis Trial (ELNT) regimen (cyclophosphamide followed by azathioprine). The study was terminated early due to an imbalance in serious infections in ocrelizumab-treated patients versus placebotreated patients. We report week 48 efficacy data for patients receiving >32 weeks of treatment (n ‫؍‬ 223) and safety results for all treated patients (n ‫؍‬ 378).Results. The overall renal response rate was 54.7%, 66.7%, 67.1%, and 66.9% in the placebo-treated, 400 mg ocrelizumab-treated, 1,000 mg ocrelizumabtreated, and combined ocrelizumab-treated groups, respectively. The associated treatment difference versus placebo for the combined ocrelizumab-treated groups was 12.7% (95% confidence interval [95% CI] ؊0.8, 26.1) (P ‫؍‬ 0.065), with similar differences observed for both ocrelizumab-treated groups. Ocrelizumab versus placebo treatment differences were apparent in patients receiving the background ELNT regimen, but not in those receiving background MMF. A numerically greater proportion of ocrelizumab-treated patients had a >50% reduction in the urinary protein:urinary creatinine ratio at 48 weeks compared with placebotreated patients (placebo-treated patients, 58.7%; 400 mg ocrelizumab-treated patients, 70.7%; 1,000 mg ocrelizumab-treated patients, 68.5%). Serious adverse events occurred in 27.2% of placebo-treated patients, 35.7% of 400 mg ocrelizumab-treated patients, and 22.0% of 1,000 mg ocrelizumab-treated patients. Corresponding serious infection rates (events/100 patientyears) were 18.7 (95% CI 12.2, 28.7), 28.8 (95% CI 20.6, 40.3), and 25.1 (95% CI 17.4, 36.1), respectively. The imbalance in serious infections with ocrelizumab ocClinicalTrials.gov identifier: NCT00626197.

ObjectivesDespite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte–macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA.MethodsIn a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)−C reactive protein (CRP)/erythrocyte sedimentation rate ≥3.2, ≥4 swollen joints despite methotrexate (MTX) were randomised 1:1:1:1 to subcutaneous mavrilimumab (150, 100, 30 mg), or placebo every other week (eow), plus MTX for 24 weeks. Coprimary outcomes were DAS28−CRP change from baseline to week 12 and American College of Rheumatology (ACR) 20 response rate (week 24).Results326 patients were randomised (150 mg, n=79; 100 mg, n=85; 30 mg, n=81; placebo, n=81); 305 completed the study (September 2012–June 2013). Mavrilimumab treatment significantly reduced DAS28−CRP scores from baseline compared with placebo (change from baseline (SE); 150 mg: −1.90 (0.14), 100 mg: −1.64 (0.13), 30 mg: −1.37 (0.14), placebo: −0.68 (0.14); p<0.001; all dosages compared with placebo).Significantly more mavrilimumab-treated patients achieved ACR20 compared with placebo (week 24: 73.4%, 61.2%, 50.6% vs 24.7%, respectively (p<0.001)). Adverse events were reported in 43 (54.4%), 36 (42.4%), 41 (50.6%) and 38 (46.9%) patients in the mavrilimumab 150, 100, 30 mg eow and placebo groups, respectively. No treatment-related safety signals were identified.ConclusionsMavrilimumab significantly decreased RA disease activity, with clinically meaningful responses observed 1 week after treatment initiation, representing a novel mechanism of action with persuasive therapeutic potential.Trial registration numberNCT01706926; results.

ObjectiveThis 24‐week, phase IIb, double‐blind study was undertaken to evaluate the efficacy and safety of mavrilimumab (a monoclonal antibody to granulocyte–macrophage colony‐stimulating factor receptor α) and golimumab (a monoclonal antibody to tumor necrosis factor [anti‐TNF]) in patients with rheumatoid arthritis (RA) who have had an inadequate response to disease‐modifying antirheumatic drugs (DMARDs) (referred to as DMARD‐IR) and/or inadequate response to other anti‐TNF agents (referred to as anti‐TNF–IR).MethodsPatients with active RA and a history of DMARD‐IR (≥1 failed regimen) or DMARD‐IR (≥1 failed regimen) and anti‐TNF–IR (1–2 failed regimens) were randomized 1:1 to receive either mavrilimumab 100 mg subcutaneously every other week or golimumab 50 mg subcutaneously every 4 weeks alternating with placebo every 4 weeks, administered concomitantly with methotrexate. The primary end points were the American College of Rheumatology 20% improvement (ACR20), 50% improvement, and 70% improvement response rates at week 24, percentage of patients achieving a Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) of <2.6 at week 24, percentage of patients with a score improvement of >0.22 on the Health Assessment Questionnaire (HAQ) disability index (DI) at week 24, and safety/tolerability measures. This study was not powered to formally compare the 2 treatments.ResultsAt week 24, differences in the ACR20, ACR50, and ACR70 response rates between the mavrilimumab treatment group (n = 70) and golimumab treatment group (n = 68) were as follows: in all patients, −3.5% (90% confidence interval [90% CI] −16.8, 9.8), −8.6% (90% CI −22.0, 4.8), and −9.8% (90% CI −21.1, 1.4), respectively; in the anti‐TNF–IR group, 11.1% (90% CI −7.8, 29.9), −8.7% (90% CI −28.1, 10.7), and −0.7% (90% CI −18.0, 16.7), respectively. Differences in the percentage of patients achieving a DAS28‐CRP of <2.6 at week 24 between the mavrilimumab and golimumab groups were −11.6% (90% CI −23.2, 0.0) in all patients, and −4.0% (90% CI −20.9, 12.9) in the anti‐TNF–IR group. The percentage of patients achieving a >0.22 improvement in the HAQ DI score at week 24 was similar between the treatment groups. Treatment‐emergent adverse events were reported in 51.4% of mavrilimumab‐treated patients and 42.6% of golimumab‐treated patients. No deaths were reported, and no specific safety signals were identified.ConclusionThe findings of this study demonstrate the clinical efficacy of both treatments, mavrilimumab at a dosage of 100 mg every other week and golimumab at a dosage of 50 mg every 4 weeks, in patients with RA. Both regimens were well‐tolerated in patients who had shown an inadequate response to DMARDs and/or other anti‐TNF agents.