FRI0313 A rituximab and belimumab combination therapy in sle patients
Authors: A.A. Mesnyankina, S.K. Soloviev, E.N. Aleksandrova, A.P. Aleksankin, A.A. Novikov, E.A. Aseeva, E.L. Nasonov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To assess the efficacy of a rituximab and belimumab combination therapy in pts with active SLE and dynamics of CD19+ B-lymphocytes count in treated pts. <h3>Methods</h3> The study included 7 SLE pts (1M/6F) with high (SLEDAI2K≥10 – 4pts.) and moderate (SLEDAI2K&lt;10- 2pts.) disease activity; out of them 1 patient had lupus nephritis, 1- vasculitis, and remaining 5 had predominantly mucocutaneous and articular manifestations of SLE. The dose of oral GCs at baseline did not exceed 20 mg/day, two pts were treated with prednisone 5 mg/day. The damage index at baseline was 0 in 3 pts,≤1 in 3pts, and ≥1 – in 1 patient. Rituximab (RTM) was administered at 500–1000 mg, with subsequent adding of Belimumab (BLM) 3 months later at a standard dosing regimen 10 mg/kg once a month during 9mo. CD19+ B- lymphocytes counts were obtained before initiation RTM (0), and subsequently after 3, 6, 9, and 12mo. Depletion of CD19+ B- lymphocytes after RTM was assessed as the decrease of B-cell counts after 3mo&lt;0,01 10*9/l, where 0 10*9/l was categorised as complete depletion, from 0001 to 0,01 10*9/l – partial depletion, and &gt;0,011 10*9/l – absence of depletion. The comparison group included 20 pts receiving a single 500–2000 mg dose of RTM. <h3>Results</h3> 6 pts demonstrated the decrease in clinical and laboratory SLE activity, starting from 3mo of follow-up (SLEDAI-2K 0 mo–Me 10, 9;16 3mo-Me 8, 4;86mo–Me 4, 2;6 9mo–Me 5,4;10 12mo–Me 2 2;6) with RTM+BLM combination therapy. The oral GCs dose was reduced to 7,5 5;10mg/day by 12mo, none of the patient required prednisone dose escalation during follow-up. There were no cases of severe infection. The damage index did not increase by 12mo. The combination therapy reduced the absolute counts of CD19+. B-cells. RTM therapy resulted in complete depletion in 2 pts, in partial depletion – in 3; in 1 patient the depletion was not documented. Addition of BLM resulted in slowing down of CD19+ B-cell repopulation (figure 1) among pts with complete and partial depletion (0mo–Me 0,11 × 10<sup>9</sup>/l[0,1;0,28], 12mo -Me 0,01 × 10<sup>9</sup>/l[0,0085; 0025]) vs pts receiving RTM monotherapy (0mo–Me 0,1 × 10<sup>9</sup>/l[0,06;0,2], 12mo -Me 0,03 × 10<sup>9</sup>/l[0,008; 0,08]). The decrease in CD19+ B-cell counts after RTM was also documented in the patient who didn't develop depletion initially (0mo–0,5 10*9/l, 12mo-0,04 10*9/l). RTM and BLM combination failure, as well as failure of standard GCS and cytostatic based therapy, was documented in one patient with cutaneous, articular and haematological SLE. <h3>Conclusions</h3> Combination therapy allows to gain control over disease activity in short time, due to the effect of RTM, while added BLM provides further prolongation of the effect achieved, minimising the risk of exacerbation. This combination may be used as a method of choice in pts with severe SLE involving vital organs, and in persistent cutaneous-articular disease and high immunological activity. Of notice is the fact, that use of RTM and BLM combination allowed to manage all pts on low and medium doses of GCs starting from RTM and BLM initiation and during the entire follow-up, thereby reducing the risk of irreversible organ damage. In these patients there were no signs of infection. <h3>Disclosure of Interest</h3> None declared