Safety and efficacy of 23-valent polysaccharide pneumococcal vaccine in patients with systemic lupus erythematosus

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.

AB0310 TOLERABILITY AND SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME, PRELIMINARY RESULTS

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

AB0309 SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Background:Vaccination of patients with autoimmune diseases with pneumococcal vaccines is necessary to prevent severe respiratory infections in this group of patients. The main issue of immunization of patients with systemic lupus erythematosus (SLE) remains the issue of safety.Objectives:The aim of the study was to study the safety of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with SLE.Methods:The study included 73 patients with a reliable diagnosis of SLE, of which women - 64, men - 9, aged 19 - 68 years. 69 patients received glucocorticoids (GC) 5-30 mg/day, 55- hydroxychloroquine (GCH), 37-cytostatics (CS), 27 – biologics (14 – rituximab (RTM), 11 – belimumab (BLM), 2-BLM and RTM). 1 dose (0.5 ml) of PPV23 was administered subcutaneously. 60 patients were examined within 1 year, 13 - within 2-3 months.Results:Vaccination tolerance was assessed in 73 patients: in 33 (45.2%) - vaccine reactions were absent, in 36 (49.3%) - local reactions of mild and moderate severity were noted (pain, swelling, skin hyperemia at the injection site of the vaccine), lasting from 2 to 7 days, in 1 (1.4%) - general weakness within 1 month, in 2 (2.7%) - mild diarrhea within 1 day. Vaccinal reactions were typical and completely reversible, did not require additional appointments. One patient (1.4%) developed a hyperergic reaction of the Artyus phenomenon type, which was arrested within 7 days by the use of antihistamines and topical GCs. None of the 60 patients, whose follow-up period was 1 year, had no exacerbations of the disease directly related to vaccination (i.e., in the next 2-3 months). Vaccination was carried out both at a low degree of activity (n = 33 (55%)) and remission (n = 6 (10%)), and at an average (n = 12 (20%)) and high (n = 9 (15%))) the degree of SLE activity. The dynamics of the SLE activity index SLEDAI-2k (Me) during the year was as follows: initially - 4 (2; 6), after 2-3 months - 2 (2; 4), after 12 months - 2 (2; 4). During the year, 7 out of 60 patients had a moderate exacerbation of the disease, which was not related to the vaccination in terms of timing: after 3.5-5 months (3), 12 months (4). An exacerbation occurred in 4 - with a decrease in the HA dose, in 1 - after psychological stress, in 1 - against the background of persistently high immunological activity and insufficient therapy, in 1 - without an increase in immunological activity. In 4 out of 7, exacerbation was manifested by skin rashes and articular syndrome, in 1 - by the development of panniculitis, in 2 - by leukopenia. All these symptoms were noted earlier in the period of exacerbation. In all, the exacerbation was quickly stopped by a moderate increase in the HA dose. In 60 patients, the dynamics of immunological markers of SLE was analyzed during the year after vaccination. There was no evidence of a significant increase in the immunological activity of SLE after vaccination with PPV-23. After vaccination, no new autoimmune phenomena have been identified. In the first 3 months. after vaccination, in isolated cases, there was a transient increase / decrease in SLE markers (a-DNA, ANF, C3, C4) with a subsequent return to the initial values, without symptoms of exacerbation of the disease.Conclusion:1. During the year of observation, no exacerbations were observed that were reliably associated with vaccination. 2. Vaccination with PPV-23 is safe for SLE patients during periods of low and moderate activity. If necessary, vaccination is possible at high activity without the development of adverse events. 3. The multidirectional dynamics of the main markers of SLE observed during the year reflects the instability of immunological parameters characteristic of SLE.Disclosure of Interests:None declared

POS0729 INFLUENCE OF VARIOUS FACTORS ON THE IMMUNOGENICITY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Background:Immunosuppressive therapy increases the risk of pneumococcal infection in patients with systemic lupus erythematosus (SLE). The therapy, as well as some features of the course of the disease, can lead to a decrease in the immunogenicity of the pneumococcal vaccine in these patients.Objectives:The aim of the study was to identify “risk factors” that negatively affect the immunogenicity of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with SLE.Methods:The study included 60 patients aged 19 - 68 years with a reliable diagnosis of SLE, disease duration from 9 months. up to 42 years old. Nine patients had high disease activity, 12 had medium, 33 had low, and 6 had remission. Therapy: 58 patients received glucocorticoids (GC) 5-40 mg / day, 46-hydroxychloroquine, 33- cytostatics (CS), 23- biologics: 12-rituximab (RTM), 10-belimumab (BLM), 1- RTM and BLM. 1 dose (0.5 ml) of PPV-23 was administered subcutaneously. During the year, standard clinical and laboratory studies were carried out, the level of antibodies to polysaccharides of the S. pneumoniae cell wall in the blood serum was determined.Results:After 1-2 months. after vaccination, 78.7% of patients showed a more than twofold increase in protective antibodies, a year later - in 56.7% of patients (“responders”). The severity of the vac-cine response did not depend on age: in the subgroup of patients under 50 years of age (n = 46), the proportion of “responders” remained 52.2%, and in patients over 50 years of age (n = 14) -50%. With different duration of the disease, the vaccine response did not differ significantly: with a disease period of up to 5 years, the vaccine response was observed in 47.6%, from 5 to 10 years - in 66.7%, over 10 years - in 55.6% of patients. Patients in remission had the lowest vaccine response (33.3%), while with high SLE activity, 100% response to the vaccine was recorded (p = 0.02), which is probably due to the fact that remission requires long-term and active immunosuppressive therapy, and patients with high activity such therapy has just been initiated or is to be. With an average and low degree of activity, the number of “respondents” was the same (50% and 51.5%, respectively). In patients receiving biologics therapy, a full-fledged vaccine response was observed less frequently than in patients without biologics (39% and 68%, respectively, p = 0.03), while no differences were found against the background of RTM and BLM therapy (41.6% and 40% of “respondents”, respectively). The effect of the duration of biologics therapy on the severity of the vaccine response was analyzed.There was a tendency for the predominance of “responders” in the group with a duration of therapy before vaccination up to 1 year, as well as in the group of initiation of biologics after vaccination, however, the differences were not statistically significant.Conclusion:RTM and BLM have a negative effect on the immunogenicity of the PPV-23 vaccine. However, if the timing of administration is observed (initiation of biologics therapy after vaccination or vaccination against the background of biologics therapy lasting less than a year), the number of “responders” increases. Further recruitment of patients is needed to clarify and confirm the results obtained.Disclosure of Interests:None declared

The Successful Vaccination of an IVIgG Naive CVID Patient with an mRNA COVID-19 Vaccine

Introduction Different subtypes of vaccines have been developed to help protect populations from COVID-19. Currently, three vaccines have been authorized by the United States Food and Drug Administration for emergency use to combat the COVID-19 pandemic. With COVID-19 vaccination rates increasing, it is important to know whether immunodeficient patients have the capacity to mount an immune response with the available vaccines. Case Report A 78-year-old female with Common Variable Immunodeficiency and anti-IgA antibodies who is naïve to IVIgG treatment responded positively to a COVID-19 mRNA vaccine. Successful seroconversion was proved by having positive COVID-19 spike protein IgG antibodies weeks after the vaccination. Her recent IgG, IgA, and IgM levels were all significantly reduced. Previously, she had no response to the polysaccharide pneumococcal vaccine, but did maintain titers afterTdap vaccination. Discussion Immunodeficient patients are a susceptible population during a pandemic. Unfortunately, there is a paucity of research on the infectivity, vaccination, and outcome of these patients during the COVID-19 outbreak. Our patient with CVID was able to respond to protein/toxoid vaccines, but did not respond to polysaccharide pneumococcal vaccine. After inoculation with an mRNA COVID-19 vaccine she was able to create COVID-19 spike protein IgG antibodies. Conclusion We present a case of successful vaccination to COVID-19 by an mRNA vaccine in an IVIgG naïve CVID patient.

Immunogenicity, Tolerability, and Clinical Effectiveness of 23-Valent Polysaccharide Pneumococcal Vaccine in Patients with Systemic Lupus Erythematosus

The aim of the work is to study the immunogenicity, tolerability, and clinical efficacy of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE). Material and methods. The study included 61 patients with a confirmed diagnosis of SLE, including 53 women, 8 men, aged 19 to 68 years. The disease activity at the time of vaccination: in 9 patients — high, in 13 — medium, in 34 — low, in 5 — remission. Therapy outline: 59 patients received glucocorticoids (GC) 5–30 mg/day in terms of prednisolone, 45 — hydroxychloroquine (GC), 33 — cytostatics (CS), 22 — genetically engineered biological drugs (GEBD): 11 — rituximab (RTM), 10 — belimumab (BLM). 23-valent polysaccharide pneumococcal vaccine in an amount of 0.5 ml (1 dose) was injected subcutaneously. Follow-up period: 9 patients — 3 months, 52 — 1 year after the vaccination. Patients were examined before vaccination, as well as in 1, 3, and 12 months after the vaccination. Results and discussion. After a year of observation, the number of «responders» to vaccination was 61.5%, «non-responders» — 38.5%. There was a decreased response to vaccine in patients receiving GEBD compared with patients who did not receive GEBD (40% and 75%, respectively), p=0.02. No differences were found against the background of RTM and BLM therapy. Administering GC in a dose exceeding 10 mg/day did not lead to a more significant decrease in response to vaccine compared to other patients. Standard local vaccination reactions of mild to moderate severity were noted in 50.8% of the patients, general reaction of mild severity — in 1 patient (1.6%), hyperergic Arthus-like reaction — in 1 patient (1.6%), the symptoms of which were relieved in 7 days. During the observation period (1 year), not a single case of exacerbation of SLE, reliably associated with the vaccination, was registered, and no new autoimmune phenomena were identified. Clinically positive dynamics was noted in the form of a decrease in the number of episodes of pneumonia, as well as acute and exacerbated chronic bronchitis, sinusitis. Conclusion. Sufficient immunogenicity, good tolerance, and clinical effectiveness of PPV-23 in patients with SLE, incl. those, who received combined immunosuppressive therapy. Further studies are needed in large groups of patients with long follow-up periods.

FRI0187 IMMUNOGENICITY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: EFFECT OF BIOLOGIC THERAPY ON THE VACCINAL RESPONSE

Background:Vaccination with 23-valent polysaccharide pneumococcal vaccine (PPV-23) in systemic lupus erythematosus (SLE) provides the prevention of severe respiratory infections in patients receiving immunosuppressive therapy. The importance of this vaccination significantly increases before and during treatment with biologics.Objectives:The aim of the study was to evaluate the immunogenicity of PPV-23 in SLE patients.Methods:The study included 52 patients with SLE, including 44 women and 8 men, aged 19 to 68 years. The duration of the disease varied from 9 months to 39 years. At the time of vaccination 7 patients had high, 10 – moderate, 30 – low activity of the disease according to SLEDAI 2K, and 5 had remission. 50 patients received glucocorticoids (GC) 5-30 mg/day equivalent to prednisone, 39 – hydroxychloroquine (GCH), 29 – cytostatics (CS), 20 – biologics: 10 – rituximab (RTM), 10 – belimumab (BLM). 1 dose (0.5 ml) of PPV23 was administered subcutaneously. During the visits, standard clinical and laboratory tests were performed, and the level of antibodies (Ab) to S.pneumoniae in blood serum was determined (VaccZymeTMPCPIg 2 kits – The Binding Site Ltd, Birmingham, UK).Results:In 1-2 months after the vaccination 78.7% of patients had a significant (more than 2 times compared to baseline) increase in the concentration of Ab to the pneumococcal cell wall polysaccharides. A year after vaccination, 61.5% of patients (“responders”) had a significant increase in the concentration of anti-pneumococcal Ab. 20 (38.5%) of 52 patients were considered “non-responders”. Median concentration of anti-pneumococcal Ab was 67[42.6; 105.8] mg/l at visit 1 (initially), 405[143.5; 468.4] mg/l at visit 2 (in 1-2 months), 166.9[77.5; 377.4] mg/l at visit 3 (in 12 months).There were clear differences in the degree of the vaccinal response depending on the therapy: in 20 patients receiving biologics full vaccinal response was achieved significantly less frequently than in patients who did not receive these drugs (40% and 75%, respectively), p=0.02. There were no obvious differences in the vaccinal response during treatment with RTM and BLM (40% of responders in both groups). The vaccinal response significantly decreased during treatment with biologics in combination with GC+/ - GCH (50% of responders). The lowest vaccinal response was observed in patients receiving biologics in combination with GC and CS + / - GCH (33.3% of responders).The analysis of the degree of the vaccinal response depending on the timing of vaccination and the time of biologics infusion was carried out. In the first group (n=6), vaccination was carried out at the optimal time in accordance with the recommendations of EULAR (2020). In the second group (n=14) vaccination was carried out in suboptimal time: during regular treatment with BLM (n=6), 1 week before the next introduction of RTM (n=2), 3-5 months after the last introduction of RTM (5), 1 week before the next introduction of RTM (n=1), 20 days after the BLM termination (n=1). In the first group with optimal vaccination terms, the number of responders was 66.7%, in the second group with suboptimal terms – 28.6%, p=0.27.Conclusion:Sufficient immunogenicity of PPV-23 was shown in SLE patients receiving immunosuppressive therapy. The negative impact of biologics on the vaccinal response was confirmed, especially if the vaccination was not performed at the optimal time in relation to the infusion of the drug or during monthly administration of BLM. If optimal vaccination terms are maintained during the treatment with or initiation of biologics (6 months after the last administration of RTM and 1 month before the next (or first) administration of RTM, 4 months after the last and 1 month before the next (or first) administration of BLM), the number of responders increases significantly. The lowest vaccinal response was obtained in patients receiving combined immunosuppressive therapy with biologics + GC+CS.Disclosure of Interests:None declared

Pneumococcal vaccination in adult patients with comorbidities: a review of the clinical practice guidelines

The review discusses national clinical practice guidelines for pneumococcal vaccination in different countries, existing approaches to adult immunization, and highlights key results of the most significant clinical studies and metaanalyses on the effectiveness of 23-valent polysaccharide pneumococcal vaccine and 13-valent conjugated pneumococcal vaccine in adults, including the elderly and patients with comorbidities.