Kathryn Hobbs

Efficacy and safety of epratuzumab in patients with moderate/severe flaring systemic lupus erythematosus: results from two randomized, double-blind, placebo-controlled, multicentre studies (ALLEVIATE) and follow-up

OBJECTIVE To evaluate epratuzumab treatment in patients with moderately-to-severely active SLE in two international, randomized, controlled trials (ALLEVIATE-1 and -2) and an open-label extension study (SL0006). METHODS Ninety ALLEVIATE patients (43% BILAG A, median BILAG score 12.0) received standard of care plus 10 total doses of placebo (n = 37) or 360 mg/m(2) (n = 42) or 720 mg/m(2) (n = 11) epratuzumab, administered across 12-week cycles for up to 48 weeks, with BILAG assessments every 4 weeks. Patients were followed for ≥ 6 months and their data combined for analysis. The primary endpoint was BILAG response at week 12 (all BILAG A scores reduced to B/C/D and B scores to C/D, no new A and <2 new B scores). Twenty-nine patients continued in SL0006, receiving 12-week cycles of 360 mg/m(2) epratuzumab; this interim analysis was performed at median 120 weeks (range 13-184) of exposure. RESULTS Both ALLEVIATE trials were discontinued prematurely because of interruption in drug supply. Exploratory pooled analyses found that responses at week 12 were 15/34 (44.1%) and 2/10 (20.0%) for epratuzumab 360 and 720 mg/m(2), respectively, vs 9/30 (30.0%) for placebo. Total BILAG scores were lower in both epratuzumab arms vs placebo at week 48 and at all but two time points. The incidence of adverse events was similar between groups. In SL0006, median total BILAG score was 8.0 (n = 29) at study entry and 7.0 (n = 19) at week 100, with no additional safety signals. CONCLUSION This initial efficacy and safety profile of epratuzumab supports its continued development for SLE treatment.

Local delivery of a recombinant adenoassociated vector containing a tumour necrosis factor α antagonist gene in inflammatory arthritis: a phase 1 dose-escalation safety and tolerability study

Objective: To examine the safety and tolerability of a single intra-articular injection of rAAV2-TNFR:Fc, an adenoassociated virus serotype 2 vector containing the cDNA for the human tumour necrosis factor–immunoglobulin Fc fusion gene (tgAAC94), in subjects with inflammatory arthritis. Methods: In a double-blind, placebo-controlled, phase 1, dose-escalation study, 15 subjects with inflammatory arthritis (14 with rheumatoid arthritis and 1 with ankylosing spondylitis) not receiving tumour necrosis factor α (TNFα) inhibitors with persistent moderate (grade 2) or severe (grade 3) swelling in a target joint due to inflammatory arthritis received a single intra-articular injection of rAAV2-TNFR:Fc at 1×1010 (n = 5) or 1×1011 (n = 6) DNase resistant particles per ml joint volume or placebo (n = 4) into a knee (n = 14) or ankle (n = 1). Safety was assessed through adverse event monitoring. As a secondary objective, changes in injected joint tenderness and swelling scores, each measured on a four-point scale, were evaluated. Results: Intra-articular injections of rAAV2-TNFR:Fc were well tolerated with no major safety issues. One event, mild knee pruritis, was considered probably related. Synovial fluid TNFR:Fc protein was not detected (nor expected) at the doses used. At 12 weeks after injection, a two-point decrease in swelling was noted in 2/11 and 2/4 subjects injected with rAAV2-TNFR:Fc and placebo, respectively. Conclusion: A single dose of intra-articular rAAV2-TNFR:Fc appears to be safe and well tolerated in subjects without concurrent systemic TNFα antagonist use. It is thus feasible to proceed with larger trials to further test the safety and efficacy of local TNFR:Fc gene transfer as a therapeutic modality for patients with inflammatory arthritis.

Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials

Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double‐blind, placebo‐controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE).

Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results from the Phase 3, Randomized, Double-blind, Placebo-controlled Trials, EMBODY™ 1 and EMBODY™ 2.

Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double‐blind, placebo‐controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE).

Long‐Term Safety and Efficacy of Epratuzumab in the Treatment of Moderate‐to‐ Severe Systemic Lupus Erythematosus: Results From an Open‐Label Extension Study

The primary objective was to assess the long‐term safety of repeated courses of epratuzumab therapy in patients with moderate‐to‐severe systemic lupus erythematosus. Secondary objectives were to assess long‐term efficacy and health‐related quality of life (HRQOL).

A retrospective analysis of low-field strength magnetic resonance imaging and the management of patients with rheumatoid arthritis

ABSTRACT Objective: To assess how in-office magnetic resonance imaging (MRI) scans of the hand/wrist or feet are utilized in a rheumatology practice to make clinical evaluations regarding therapeutic options for rheumatoid arthritis (RA) patients. Methods: In a large clinical practice, a retrospective review was conducted on the first 300 RA patients who had office-based MRI scans at baseline. Information was collected on demographics, baseline therapy, and whether any change in therapy occurred at the time of the MRI scans. MR images of the affected wrist were obtained with a low-field strength dedicated extremity unit. Results: Of the 300 patients, 99 patients (33%) had MRIs that exhibited signs of erosions, joint space narrowing, or bone edema. These patients were classified as MRI-positive. The remaining 201 patients (67%) were classified as MRI-negative. A substantial majority (85%) of MRI-positive patients received a change in their therapeutic regimen, compared with only 9.5% of the MRI-negative patients ( p < 0.001). In the 84 MRI-positive patients who had their therapy changed, 65% received a new prescription for a biologic or an increase in the dose of their existing biologic and 34% of the MRI-positive patients received a DMARD. In the 19 MRI-negative patients with a therapeutic change, 11% received a biologic agent and 88% received a DMARD. The major limitation of this study is that it was a retrospective analysis and the assessments of MRI findings were qualitative. Conclusion: In this large population of RA patients, there was an association between MRI detection of joint space narrowing, erosions, and/or bone edema and change in therapeutic management.