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

2020 ◽  
Vol 65 (5-6) ◽  
pp. 35-40
Author(s):  
G. M. Tarasova ◽  
B. S. Belov ◽  
M. V. Cherkasova ◽  
S. K. Soloviev ◽  
E. A. Aseeva ◽  
...  

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.

2021 ◽  
Vol 15 (3) ◽  
pp. 50-56
Author(s):  
G. M. Tarasova ◽  
B. S. Belov ◽  
M. V. Cherkasova ◽  
E. A. Aseeva ◽  
T. M. Reshetnyak ◽  
...  

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.


2018 ◽  
Vol 56 (4) ◽  
pp. 433-438 ◽  
Author(s):  
G. M. Tarasova ◽  
B. S. Belov ◽  
D. V. Bukhanova ◽  
M. V. Cherkasova ◽  
S. K. Solovyev ◽  
...  

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.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 677.1-677
Author(s):  
G. Tarasova ◽  
B. Belov ◽  
M. Cherkasova ◽  
S. Solovyev ◽  
E. Aseeva ◽  
...  

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


2018 ◽  
Vol 17 (2) ◽  
pp. 110-125
Author(s):  
Ekaterina I. Alexeeva ◽  
Tatiana M. Dvoryakovskaya ◽  
Irina P. Nikishina ◽  
Rina V. Denisova ◽  
Nadezhda S. Podchernyaeva ◽  
...  

The article presents modern ideas about the treatment of systemic lupus erythematosus (SLE). The details of the management of patients with SLE during immunosuppressive and genetically engineered therapy is given. The article also reflects the aspects of rehabilitation, prevention of exacerbations, and follow-up care of children with SLE. The criteria for assessing the quality of medical care for children with SLE are presented. The detailed information on systemic lupus erythematosus for patients with SLE and their parents is outlined specifically.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 614.2-615
Author(s):  
G. Tarasova ◽  
B. Belov ◽  
M. Cherkasova ◽  
E. Aseeva ◽  
T. Reshetnyak ◽  
...  

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


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1180.2-1180
Author(s):  
G. Tarasova ◽  
B. Belov ◽  
M. Cherkasova ◽  
E. Aseeva ◽  
T. Reshetnyak ◽  
...  

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


2014 ◽  
Vol 26 (2) ◽  
pp. 459-467 ◽  
Author(s):  
L. P. C. Seguro ◽  
C. B. Casella ◽  
V. F. Caparbo ◽  
R. M. Oliveira ◽  
A. Bonfa ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Liuye Huang ◽  
Yuan Yang ◽  
Yu Kuang ◽  
Dapeng Wei ◽  
Wanyi Li ◽  
...  

Objective. Systemic lupus erythematosus (SLE) is an autoimmune disease identified by a plethora of production of autoantibodies. Autoreactive T cells may play an important role in the process. Attenuated T cell vaccination (TCV) has proven to benefit some autoimmune diseases by deleting or suppressing pathogenic T cells. However, clinical evidence for TCV in SLE is still limited. Therefore, this self-controlled study concentrates on the clinical effects of TCV on SLE patients. Methods. 16 patients were enrolled in the study; they accepted TCV regularly. SLEDAI, clinical symptoms, blood parameters including complements 3 and 4 levels, ANA, and anti-ds-DNA antibodies were tested. In addition, the side effects and drug usage were observed during the patients’ treatment and follow-up. Results. Remissions in clinical symptoms such as facial rash, vasculitis, and proteinuria were noted in most patients. There are also evident reductions in SLEDAI, anti-ds-DNA antibodies, and GC dose and increases in C3 and C4 levels, with no pathogenic side effects during treatment and follow-up. Conclusions. T cell vaccination is helpful in alleviating and regulating systemic lupus erythematosus manifestation.


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