Controlling inflammation and preventing organ damage are the goals of treatment of moderate to severe systemic lupus erythematosus (SLE). Corticosteroids have been the treatment gold standard, but such therapy is often associated with serious long-term complications. New therapies focused on inhibition of B-cell activation while avoiding total cellular depletion are in development. The only currently available agent is belimumab, a monoclonal antibody against the soluble B-lymphocyte stimulator, but a new monoclonal antibody drug, epratuzumab, has now been studied.
Results of an open-label extension (OLE) of the Phase IIb Multi-Center, Open-label, Follow-up Study to Assess Safety and Efficacy of Epratuzumab in Serologically-positive Systemic Lupus Erythematosus Patients With Active Disease Who Participated in Study SL0007 (EMBLEM) randomized controlled trial (NCT00660881) confirm epratuzumab is well tolerated and associated with improvements in disease activity and quality of life (QoL) in patients with moderate to severe SLE.1
Epratuzumab, a novel B-cell modulator, binds to the B-cell inhibitory coreceptor CD22. The safety and efficacy of epratuzumab were assessed in the Alleviate Lupus Affliction with Epratuzumab and Validate its Autoimmune Safety and Efficacy (ALLEVIATE)-1 and -2 randomized controlled trials (NCT00111306 and NCT00383214, respectively) and the phase IIb EMBLEM trial (NCT00624351).2,3
The OLE acted as a continuation of the 12-week dose-ranging EMBLEM trial through which the long-term safety and efficacy of epratuzumab and health-related QoL (HRQoL) in patients with moderate to severe SLE could be evaluated. Patients eligible for participation in the OLE were those who completed the trial or discontinued blinded treatment due to lack of efficacy but completed ≥ 8 weeks of the trial.
The OLE population consisted of 203 patients, of which 113 continued until the study’s end. The regimen was 1200 mg epratuzumab infusions at weeks 0 and 2 of every 12-week cycle plus standard of care for up to 3.2 years. Efficacy was measured by combined treatment response, the British Isles Lupus Assessment Group (BILAG) score, the Systemic Lupus Erythematosus Disease Activity Index score, and physician and patient global assessment of disease activity. HRQoL was assessed using the Medical Outcomes Study Short Form 36 (SF-36. Treatment-emergent adverse events (TEAEs), including and serious TEAEs, were documented. Total corticosteroid dose also was assessed.
Sustained Long-term Improvement
The multi-center research team, headed by Daniel J. Wallace, MD, of Cedars-Sinai Medical Center in Los Angeles, California, found that efficacy and HRQoL in the OLE study was comparable with that seen in the EMBLEM trial. BILAG score increased from 35% at OLE baseline screening to 64% at week 108, and therapeutic response increased from 34% at baseline to 41% at last visit among patients who had received the study drug during the trial. For those who received a placebo during the trial, response increased from 26% to 46% during the OLE. Clinically meaningful improvements were seen in SF-36 physical and mental component summary scores in 71% and 59% of patients, respectively, by week 108. With regard to corticosteroid dose, the median was reduced from 10.0 mg/d at OLE screening to 5.0 mg/d at week 108.
TEAEs were reported in 192 (95%) patients, and the most common were infections and infestations (68 %). Serious TEAEs were reported in 51 patients (25%), and serious infections developed in 14 (7%), but no incidence of pneumonia, herpes zoster, or tuberculosis was reported.
Summary and Clinical Applicability
This OLE demonstrated that epratuzumab maintains efficacy with long-term use, and long-term use is not associated with heightened risk of adverse events. These results suggest that epratuzumab may be a much-needed new addition to the therapeutic armamentarium in the management of moderate to severe SLE.
Limitations and Disclosures
A limitation of this study was the potential bias introduced by patient dropouts in the open-label design.
This study was funded by UCB Pharma. The following statement accompanied the published manuscript: “In addition to content approval by the authors, UCB Pharma signed off on the manuscript following a full review to ensure that the data presented in the publication are scientifically, technically, and medically supportable and did not contain any information that has the potential to damage the intellectual property of UCB Pharma1.“
1. Wallace DJ, Hobbs K, Clowse ME, et al. Long-term safety and efficacy of epratuzumab in the treatment of moderate-to-severe systemic lupus erythematosus: results from an open-label extension study. Arthritis Care Res (Hoboken). 2016;68(4):534-543.
2. Wallace DJ, Gordon C, Strand V, et al. 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. Rheumatology (Oxford). 2013;52(7):1313-1322.
3.Wallace DJ, Kalunian K, Petri MA, , et al. Efﬁcacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus:results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study. Ann Rheum Dis. 2014;73(1):183-190.