ObjectivesTo 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.MethodsThe study included 7 SLE pts (1M/6F) with high (SLEDAI2K≥10 – 4pts.) and moderate (SLEDAI2K<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<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 >0,011 10*9/l – absence of depletion. The comparison group included 20 pts receiving a single 500–2000 mg dose of RTM.Results6 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 × 109/l[0,1;0,28], 12mo -Me 0,01 × 109/l[0,0085; 0025]) vs pts receiving RTM monotherapy (0mo–Me 0,1 × 109/l[0,06;0,2], 12mo -Me 0,03 × 109/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.Abstract FRI0313 – Figure 1Dynamics in CD19+ B-lymphocytes in pts treated RTM and RTM+BLM combination therapyConclusionsCombination 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 combi...

Objective: to study the safety and efficacy of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE).Patients and methods. The study included 75 patients with definite diagnosis of SLE at the age of 19–68 years, 10 (13%) of them had high SLE activity, 18 (24%) – moderate, 42 (56%) – low, in 5 (7%) patients the disease was in remission. PPV-23 was injected subcutaneously in a single dose of 0.5 ml. In 60 patients the follow-up period was ≥12 months, in 15 – from 2 to 6 months. Patients were examined before and 1, 3 and 12 months after immunization.Results and discussion. In 38 (50.7%) patients, standard local vaccination reactions of mild and moderate severity were noted, in 1 (1.3%) – a general reaction of mild severity, in 2 (2.7%) – mild diarrhea during 1 day, in 1 (1.3%) – a hyperergic reaction of the Artyus phenomenon type, the symptoms were relieved within 7 days. During 12 months of follow-up, neither exacerbations of SLE, reliably associated with vaccination, nor new autoimmune phenomena, were detected. After 1 year of observation, the number of responders to vaccination was 58%, non-responders – 42%. The duration and activity of the disease, age over 50 years, glucocorticoid therapy > 10 mg per day, did not significantly affect the vaccine response. There was a decrease in the immune response in patients on biologic DMARDs (bDMARDs) therapy compared to patients without such treatment (43 and 68% of cases, respectively), p=0.058. There was no difference between rituximab and belimumab treated subjects. There was a tendency for the prevalence of vaccination responses among patients, who received bDMARDs <1 year before immunization, as well as among patients in whom this therapy was initiated after the administration of PPV-23. There was a positive trend in decrease of pneumonia, acute and exacerbations of chronic bronchitis episodes and sinusitis.Conclusion. Sufficient immunogenicity, good tolerability and clinical efficacy of PPV-23 in patients with SLE, including those who received combined immunosuppressive therapy, have been shown. The use of bDMARDs reduces the number of patients with a vaccine response. The number of responders to vaccination increases when immunization is carried out before the initiation of therapy with bDMARDs or when this therapy is initiated <1 year before immunization. Further long-term prospective studies in large patient cohorts are required.

Objective: to investigate the safety and immunogenicity of 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE). Subjects and methods. The investigation enrolled 30 patients with a reliable diagnosis of SLE; of them there were 27 women and 3 men at the age of 19 to 62 years. The disease duration ranged from 9 months to 20 years. At the time of inclusion in the investigation, the disease activity was high in 2 patients, moderate in 3, and low in 20; five patients were in remission. During a year before vaccination, pneumonia was detected in 5 (16.7%) of the 30 patients; there were a total of 18 episodes of various respiratory and ENT infections. The patients were examined at baseline and at 1, 3 and 12 months after vaccination. Standard clinical and laboratory studies and a detailed blood immunological analysis were carried out at visits. The levels of IgG antibodies to capsular polysaccharide pneumococcus were determined during each visit. Twenty-nine patients received glucocorticoids (GCs) at a dose of 5–30 mg/day; 24 – hydroxychloroquine; 14 – cytostatics (CS); 10 – biological agents (BAs) (5 – rituximab, 5 – belimumab). A single dose of 0.5 ml of PPV-23 (Pneumo 23, Aventis) was subcutaneously injected into the upper outer arm. Vaccination was done during the ongoing therapy with GC/CS and belimumab, as well as at least 1 month before the first (next) administration and/or 4.5–5 months after the last rituximab infusion. Results and discussion. 60% of patients were observed to have mild and moderate standard local vaccine reactions; 1 (3.3%) patient had a local hyperergic reaction eliminated within 7 days of the local application of antihistamines and GCs. During the follow-up, there was no SLE exacerbation significantly associated with the vaccination performed. No new autoimmune phenomena were found in any of the cases. A year after vaccination, a significant (2-fold or more) increase in anti-pneumococcal antibody levels remained in 19 (63.3%) patients (respondents); 36.7% of patients were nonrespondents. Among the patients who received a BA, the non-responders were significantly more than among those who did not take the drug (7 (70%) and 4 (20%), respectively) (p = 0.01). When treated with rituximab and belimumab, the number of non-respondents was comparable (4 and 3, respectively). The immunogenicity of PPV-23 was independent of the degree of SLE activity: the vaccine response was absent in 1 out of the 5 patients with high (n = 2) and medium (n = 3) SLE activities, as well as in 10 out of the 25 patients with low disease activity and remission. There was no development of considerable adverse reactions after vaccination in patients with high and medium SLE activity. The overall clinical efficiency of vaccination was 93.3%. Conclusion. Thus, PPV-23 shows a good tolerability and a sufficient immunogenicity in patients with SLE. There is a need for further investigations conducted in large samples of patients during long-term follow-ups in order to more fully evaluate the clinical efficacy, tolerability, and immunogenicity of PPV-23.

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Background:Antiphospholipid syndrome (APS) is an autoimmune disease often associated with severe, life-threatening vascular complications. The majority of patients (and in case of secondary APS, in 100% of cases) receive immunosuppressive therapy. Immunization with pneumococcal vaccines in patients with both primary APS (PAPS) and APS+SLE or secondary (sAPS) is necessary to prevent severe respiratory infections in these patients.Objectives:Purpose of the study - to study the tolerance and safety of 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with PAPS and sAPS.Methods:At this stage, the study included 28 patients with APS, of which 10 with PAPS, 18 with sAPS proceeding against the background of systemic lupus erythematosus (SLE), of which 23 women (82%), 5 men (18%). The average age (Me) of patients was 43 (35.5; 53.0) g. 20 patients received glucocorticoids (GC) 5-30 mg/day equivalent to prednisone, 17- hydroxychloroquine, 6- cytostatics (3-cyclophosphamide, 2-azathioprine, 1- mycophenolate mofetil), 8- biologics: 5-rituximab (RTM), 3-belimumab (BLM); 20-received anticoagulants (direct-10, indirect-10).1 dose (0.5 ml) of PPV-23 was administered subcutaneously. The follow-up time was 1 year in 23 patients and 5-5.5 months in 5-5.5 months. During the visits, standard clinical and laboratory tests were performed, immunological blood test and the level of antibodies to S.pneumoniaeResults:Vaccination was well tolerated in all patients. In 29% of cases, vaccine reactions of mild severity were observed: in 7 (25%) - a local reaction (pain in the arm for 1-3 days-at 7, redness up to 2 cm at the injection site-at 1), in 1 (3,6%), the patient experienced general weakness (moderately pronounced) for 1 month. Vaccinal reactions were completely reversible and did not require additional prescriptions. Post-vaccination complications develop, as a rule, in the first 1-2 months after vaccination. During the observation period, none of the patients had an exacerbation of the disease, reliably associated with the vaccination. There was no recurrence of thrombosis, both in patients receiving anticoagulant therapy and without it. No new autoimmune phenomena, both clinical and laboratory, were identified. The dynamics of the production of anti-streptococcal antibodies during the year was followed in 16 patients. One year after vaccination, 31% of patients showed a significant (more than 2-fold compared to the initial) increase in the concentration of antibodies to polysaccharides of the cell wall of S. pneumoniae (“responders”), 69% of patients were “non-responders” to the vaccine. At the same time, all 5 patients with PAPS were “non-responders”, and 45.5% “respondents” with sAPS.Conclusion:Preliminary results show that patients with APS tolerate PPV-23 vaccination well. In the next post-vaccination period, exacerbations of the disease, thrombosis were not recorded. Attention is drawn to the large number of “non-responders” in PAPS, however, to obtain statistically reliable results, it is necessary to continue the study and recruit more patients.Disclosure of Interests:None declared