Abetimus sodium

> ‘All other things being equal, we may assume the superiority of the demonstration which derives from fewer postulates or hypotheses’—Aristotle Therapeutic options for systemic lupus erythematosus (SLE) are still limited. A number of conventional immunosuppressives are used along with glucocorticoids and antimalarials, but the successes of biological therapies in the arthritides have not been duplicated for SLE. To date, only one biologic succeeded in phase III trials1 ,2 and was approved for use in SLE, but its proper role in the overall management of the patient with SLE has remained incompletely defined.3 Rituximab is used off-label on the strength of many observational studies,4 ,5 but two large trials failed to demonstrate efficacy.6 ,7 A distressingly large number of biologics failed in late-stage trials, where some have completely disappeared from further consideration (the B-cell tolerising oligonucleotide construct abetimus,8 the anti-CD20 monoclonal ocrelizumab9); for some others, the future looks bleak (the BLyS antagonist tabalumab,10 ,11 the anti-CD22 monoclonal epratuzumab) and for yet others, investigators and sponsors are struggling to find the best way forward (the T-cell costimulation blocker abatacept,12 ,13 the BLyS/APRIL antagonist atacicept14 ,15). The failure of many SLE trials may have been due, at least in part, to the simple fact that the drugs being studied were not very effective, but it has also been suggested that clinical trial methodology for SLE has been suboptimal. Any positive or successful trial could therefore give us the dual benefit of moving the field forward with a new compound, while also providing us with useful lessons for the design of clinical trials. The interferon (IFN) system has been identified as a key pathway in the immunopathogenesis of SLE.16–22 It was therefore logical to develop specific IFN …

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease that significantly affects health-related quality of life (HRQOL): physical, psychologic, mental, and social aspects of well-being that are influenced by disease, in the context of life experiences and expectations specific to each patient1. A relapsing, remitting chronic disease, SLE results in disability in 20%–40% of afflicted young and middle-aged women and men2. In patients with SLE, HRQOL is influenced by disease activity and symptoms of fatigue, depression, pain, sleep disturbances, and cognitive dysfunction3. Across 5 randomized controlled trials (RCT) in SLE, baseline HRQOL scores were low and were similar to those of subjects following myocardial infarction or with chronic congestive heart failure4. Lower scores were highly correlated with history of renal disease, presence of anti-dsDNA antibodies, higher disease activity scores by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and/or Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA-SLEDAI), hypocomplementemia, African American descent, and age. A variety of therapeutic interventions, including pharmacologic and biologic therapies, have been shown in RCT to improve HRQOL, including prasterone, mycophenolate mofetil, abetimus sodium, oral contraceptive, and hormone replacement therapy in the SELENA trials, as well as monoclonal antibodies epratuzumab and belimumab5,6,7,8. In 1998, an international consensus conference on outcome measures in rheumatology (OMERACT 4) recommended that 4 core domains be assessed in RCT and longitudinal observational studies (LOS) in SLE: disease activity, HRQOL, adverse events, and damage9. OMERACT has also recommended that both generic and disease-specific instruments be utilized to measure HRQOL. Ongoing efforts to develop promising therapies for SLE have demonstrated the importance of including patient-reported outcomes (PRO) to assess HRQOL in RCT. Measurement of HRQOL adds a unique dimension to … Address correspondence to Dr. Strand; E-mail: vstrand{at}stanford.edu