Tuesday, 18 Dec 2018

You are here

SynBioSe: Combo Rituximab and Belimumab Succeeds in Severe Refractory Lupus

One of the driving pathogenic mechanisms in systemic lupus erythematosus (SLE) is the generation of immune complexes capable of inducing netosis (NET formation) and NET-derived DNA that may be an amplifying autoantigen and give rise to anti-nuclear autoantibodies (ANAs). 

Researchers from Leiden University Medical Center in The Netherlands sought to target autoreactive plasma cells and interfere with immune complex formation and netosis in SLE by treating patients with a combination of rituximab (RTX) and belimumab (BLM).

The SynBioSe study was a 2A, open-label, single arm proof-of-concept study that treated 16 SLE patients who had severe, refractory disease despite aggressive immunosuppressive treatments.  All had active disease with a mean SLEDAi of 18 and the majority had lupus nephritis and were on mycophenolate. 

Patients underwent CD20-mediated B-cell depletion with rituximab (1000 mg on days 0 and 14) followed by  belimumab 10 mg/kg (on days 28, 42, 56, and every 4 weeks thereafter). The protocol called for all to have their glucocorticoids (60 to 7.5 mg/day) and mycophenolate tapered (to zero). The study endpoints at 24 weeks examined SLEDAI scores, immunologic effects (autoantibodies, NET formation, etc) and safety outcomes. 

As expected, they demonstrated a significant rise in BlyS levels following RTX therapy, which was subsequently diminished with belimumab treatment. RTX + BLM led to specific reductions in ANAs, autoantibodies and dimunution of NET formation.

Significant clinical improvement was also seen with a low lupus disease activity state achieved in 10 patients, renal responses in 11 patients and concomitant immunosuppressive medication (MMF) tapered in 14 of the 16 patients.

The trial was a highlight presentation from EULAR 2017 meeting and is now published in the Journal of Autoimmunity.

Combination therapy with RTX + BLM appears to effectively reduce autoantibodies and excessive NET formation, with significant clinical benefits in severe refractory SLE patients.  Future studies with this intriguing combination are warranted.

ClinicalTrials.gov NCT02284984.

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

Genetic Diagnosis for Previously Undiagnosed Disorders

The NEJM has reported the NIH's Undiagnosed Diseases Network (UDN) study results of genetically identifying new diseases from prospectively followed persons with undiagnosed disorders. The UDN was formed in 2014 as a network of seven clinical sites, two sequencing cores, a coordinating center, central biorepository, a metabolomics core, and a model organisms screening center. It was established to apply a multidisciplinary model in the evaluation of the most challenging cases and to identify the biologic characteristics of newly discovered diseases.

SLE and Risk of Malignancy

The risk for cancer in systemic lupus erythematosus (SLE) patients has been inconsistently studied.  A new metanalysis shows that SLE has an increased risk for 16 specific cancers and decreased risk for prostate cancer and cutaneous melanoma. 

The Benefits of a Lupus Clinic

A comparative cohort study assessing the quality of care in patients with systemic lupus erythematosus (SLE) suggests that a dedicated lupus clinic has better quality measure performance compared to lupus management in a general rheumatology clinic.

A study from Rush University enrolled 150 consecutive SLE patients - with 73 followed in the general rheumatology clinic and 77 followed in a dedicated lupus clinic. 

Diagnosing Early Lupus from Mimics

A multicenter study of early systemic lupus erythematosus (SLE) patients examined manifestations at disease onset and found that certain clinical features can help to distinguish early SLE from other SLE‐mimicking conditions. 

High CV Risk in Lupus

Patients with systemic lupus erythematosus (SLE) remain at risk for accelerated atherosclerosis, and important questions have yet to be answered, British investigators reported.