Ofatumumab Safe, Effective for B Cell Depletion in Rituximab-Intolerant SLE

Patients with systemic lupus erythematosus (SLE) with aggressive disease who have experienced rituximab infusion reactions may benefit from a switch to ofatumumab as an alternative for B cell depletion, according to a retrospective case series recently published in Rheumatology. The results of the trial revealed good efficacy and an acceptable safety profile for the monoclonal antibody.

Despite clinical success with rituximab in patients with SLE who have indications for B cell depletion, individuals often develop allergic reactions that make further therapy untenable. The lower immunogenicity of humanized ofatumumab makes this treatment an excellent candidate to replace rituximab as the depleting agent in patients intolerant to rituximab.

Between 2012 and 2015, 16 rituximab-intolerant patients with SLE received ofatumumab therapy, and 14 participants (100% women; median age, 34; median SLE duration, 9.2 years) tolerated the infusions and were subjected to further analysis. This cohort was heavily pre-treated, with a 4 g median rituximab cumulative dose and 50% had previously received cyclophosphamide. Of the 14 individuals, 12 had lupus nephritis as an indication for B cell depletion.

After analysis of the 14 remaining patients, 12 achieved B cell depletion (median time, 14 days), demonstrating cell counts and kinetics comparable to those seen with rituximab. Serological biomarker levels — for antinuclear antibodies, anti-double stranded DNA antibodies and complement levels — were improved in this cohort. Results also showed that 50% of the patients with lupus nephritis had reached renal remission at 6-month follow-up.

There were 5 non-responders with progressive disease who did not respond to cyclophosphamide augmentation, and 4 eventually experienced systemic flares. The median long-term follow-up in the 14 participants was 28 months. During this period, 3 patients developed a total of 5 serious infections, although none were atypical or opportunistic. No persistent neutropenia, malignancies, or deaths were reported.

Study limitations included the small size, lack of controls and heterogeneity, inability to identify obvious response predictors, and inability to analyze the B cell effects in detail.

Treatment with ofatumumab offered an alternative to B cell depletion in patients allergic to rituximab, yielding equivocal clinical and laboratory improvements without provoking many infusion reactions. Its utility in treating resistant SLE should continue to be explored to better understand its overall safety and efficacy in this population.

Disclosures: LL has received honoraria for advisory boards and lectures from Aurinia, Genentech, GSK, Hoffman La Roche, and UCB and has received research support from Hoffman La Roche. All other authors have declared no conflicts of interest.

Reference

Masoud S, Mcadoo SP, Bedi R, Cairns TD, Lightstone L. Ofatumumab for B cell depletion in patients with systemic lupus erythematosus who are allergic to rituximab [published online March 19, 2018]. Rheumatology (Oxford).  doi:10.1093/rheumatology/key042