Rituximab Therapy Research Articles

Case report: orthostatic hypotension as the first presentation of progressive encephalomyelitis with rigidity and myoclonus (PERM) with multiple autoimmune antibodies

IntroductionStiff person syndrome (SPS) is a rare disease characterized by axial and lower-extremity muscle rigidity, muscle spasm, and pain. Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a variant of SPS. This case is particularly notable for its uncommon initial symptom: orthostatic hypotension, coupled with the presence of multiple antibodies. Such a presentation is a rarity in the context of PERM, thus providing a fresh and unique angle for both diagnosis and treatment.Case presentationThis case presents a 71-year-old man who was ultimately diagnosed with progressive encephalomyelitis with rigidity and myoclonus (PERM). His initial symptom was orthostatic hypotension, and we detected multiple antibodies such as GlyR antibody, GAD antibody, GM1-IgG and GQ1b-IgG in his serum. The patient showed partial response to glucocorticoid and immunoglobulin therapies, but as the disease recurred and progressed, plasma exchange, rituximab, and cyclophosphamide immunosuppressive therapy was administered, the prognosis remained poor. During follow-up after treatment, the patient developed pulmonary embolism and cardiac arrest, and died.ConclusionPERM exhibits diverse manifestation and pathogenic mechanisms. Immune heterogeneity affects clinical symptoms and prognosis. Cases of PERM combined with orthostatic hypotension and various antibodies have rarely been reported, the incidence and the specific mechanism is unknown, underscoring the need for further research. This case report underscores the importance of recognizing the diverse clinical presentations of PERM and the challenges in its diagnosis and management. It highlights autonomic dysfunction may be as the initial symptom of PERM. Moreover, it emphasizes the limitations of current treatment modalities and the necessity for further research to elucidate the underlying mechanisms and optimize therapeutic approaches for this debilitating autoimmune condition.

Bendamustine–rituximab elicits dual tumoricidal and immunomodulatory responses via cGAS–STING activation in diffuse large B-cell lymphoma

BackgroundBendamustine–rituximab (BR) therapy stands out as a promising alternative for elderly patients with diffuse large B-cell lymphoma (DLBCL), demonstrating notable efficacy when conventional regimens pose challenges. Despite its clinical success,...

Combination therapy of dexamethasone, rituximab, and cyclosporine for adults with primary immune thrombocytopenia: a prospective observational study

ABSTRACT Background To assess the effectiveness of the combination of dexamethasone, rituximab, and cyclosporine in treating adults with primary immune thrombocytopenia (ITP). Research design and methods This prospective study enrolled consecutive adult patients diagnosed with ITP at the 967th Hospital of the Chinese People’s Liberation Army Joint Service Support Force Hospital between November 2019 and February 2023. Results Twenty-eight patients (13 males, median age 43.5 years) were included. All patients previously experienced ineffective or relapsed ITP, with a median disease duration of 26.5 (range, 7-72) months. At baseline, the median platelet (PLT) count was 13.5 × 109/L (8.25-20 × 109/L). Following treatment, the PLT counts were significantly increased at weeks 1, 3, and 4. The early response rates at weeks 1 and 4 were 82.1% (23/28 patients) and 71.4% (20/28 patients), respectively. The 1-, 3-, and 6-month response rates were 71.4% (20/28), 67.9% (19/28), and 75% (21/28). The treatment-free survival rates at 12 and 24 months were 82.35% (14/17) and 71.43% (10/14), respectively. Six patients experienced transient adverse reactions. Conclusions The combination of dexamethasone, rituximab, and cyclosporine may present a promising therapeutic option for patients with refractory ITP, with good tolerability and mild adverse reactions.

Neutrophil-to-Lymphocyte Ratio as a Biomarker for Clinical Response After Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis.

Systemic sclerosis is a complex disease that affects various target organs, making it difficult to assess response and determine remission or relapse. A baseline Neutrophil-to-Lymphocyte Ratio (NLR) >2.95 is associated with severe progressive skin and lung disease and decreased 5-year survival in systemic sclerosis (SSc). However, it is unknown whether NLR changes in response to treatment. To retrospectively evaluate NLR changes as a biomarker for treatment response in SSc. Progressive diffuse SSc patients who were treated with autologous hematopoietic stem cell transplantation (AHSCT group), with combination therapy of rituximab and mycophenolate mofetil (combination group) or CAR-T cell therapy (CAR-T group) were recruited, along with healthy controls (HC group). NLR, modified Rodnan Skin Score (mRSS) and forced vital capacity (FVC)% predicted were repeatedly assessed over 2 years. Fifteen patients were recruited in the AHSCT group, 15 in the combination group, and six patients in the CAR-T group. Baseline mean NLR was high (>2.95) in AHSCT, combination groups, and CAR-T compared with HC. All treatment arms showed a statistically significant decrease in mRSS values and an increase in FVC% at each time point up to 12 months. In a linear mixed model, NLR significantly decreased up to 24 months only in the AHSCT group. NLR correlated with mRSS and FVC exclusively in the AHSCT group. NLR increased above 3 in two patients who experienced a relapse after AHSCT. NLR is a simple biomarker that correlated with outcome measures in SSc following AHSCT, but not with conventional therapy or CAR-T therapy. It is suggested that a decrease in NLR following AHSCT may indicate remission, whereas an increase may be associated with exacerbation. Further research is needed to validate these novel findings.

Management and long-term outcome of recurrent idiopathic FSGS in pediatric kidney transplant recipients

Focal segmental glomerulosclerosis (FSGS) is a major cause of pediatric kidney failure. Most cases of FSGS in children are idiopathic and have a high risk of post-transplantation recurrence and graft loss. Common treatments for recurrent FSGS (rFSGS) post-transplantation include plasmapheresis, immunoadsorption, and/or immunomodulatory therapy. This study retrospectively evaluated the efficacy and safety of early plasmapheresis followed by rituximab for inducing and maintaining remission in rFSGS. Between 2014 and 2023, 8 of 65 pediatric kidney transplant recipients at our center were diagnosed with idiopathic FSGS. rFSGS was diagnosed based on nephrotic range proteinuria with no other cause and managed with plasmapheresis. Rituximab therapy was used for those who did not achieve complete remission with prolonged plasmapheresis or remained plasmapheresis dependent. 6 of 8 (75%) transplant recipients with idiopathic FSGS experienced rFSGS. All patients achieved partial or complete remission with plasmapheresis, with response times ranging from 8 to 379 days (median 13 days). Rituximab therapy was introduced for 5 plasmapheresis-dependent patients, leading to sustained remission and cessation of plasmapheresis in 3 patients, while 2 showed improved proteinuria and reduced plasmapheresis frequency. Adverse effects included rituximab-induced serum sickness in one patient and one mild allergic reaction. One patient experienced graft loss due to humoral rejection, but no grafts were lost to rFSGS, and all other grafts remained functional over an average follow-up of 50 months. Early plasmapheresis followed by rituximab therapy effectively induces remission in most post-transplantation rFSGS cases, is well tolerated, and prevents graft loss. Larger studies are needed to confirm these findings.

Long-term outcome of autologous haematopoietic stem cell transplantation in patients with systemic sclerosis: a comparison with patients treated with rituximab and with traditional immunosuppressive agents

BackgroundAutologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there is still a paucity of data comparing AHSCT with rituximab (RTX). Aim of the study is to retrospectively compare, in patients with dcSSc, the effectiveness of AHSCT with that of RTX and CIT.MethodsThirty-five dcSSc AHSCT-treated patients were compared with 29 and 36 matched cases treated with RTX and CIT, respectively. The patients were followed up for 5 years by assessing selected outcome measures every year. Overall survival, modified Rodnan skin score (mRSS), lung function tests (FVC and DLCO), and the revised EUSTAR Activity Index (REAI) were the outcome measures chosen to evaluate the therapy efficacy.ResultsAHSCT was significantly more effective than RTX and CIT in prolonging survival, inducing a rapid reduction of the mRSS and REAI and maintaining the baseline level of lung function tests for a longer time. RTX therapy was also superior to CIT in reducing REAI, mRSS and in saving lung function.ConclusionAHSCT is more effective than both RTX and CIT in prolonging survival and inducing prolonged remission in patients with rapidly progressive dcSSc.

Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis

ObjectivesB-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral B-cell development to identify...

Pharmacoeconomic analysis of rituximab and belimumab therapy in patients with systemic lupus erythematosus

The progressive course of systemic lupus erythematosus (SLE) with high activity and severe internal organs involvement requires the prescription of expensive biologic disease-modifying antirheumatic drugs (bDMARDs), rituximab (RTM) and belimumab (BLM), whose comparative clinical and economic efficacy has not been adequately studied.Objective: to evaluate the clinical and economic efficacy of RTM and BLM therapy in patients with SLE.Material and methods. The study included 50 SLE patients who were divided into two groups and received RTM (group 1, n=25) or BLM (group 2, n=25) therapy for 12 months. The clinical and economic analysis was performed with the cost-effectiveness method using the cost-per-responder (CPR) model. A clinically significant improvement in SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index modified 2K; Δ ≥4) was considered a response to therapy. Direct and indirect costs were considered in the analysis.Results and discussion. Against a background of therapy, there was a decrease in SLE activity with a decrease in median SLEDAI-2K in group 1 from 12 [10.5; 18] to 8 [4; 10] and in group 2 from 10 [8; 14.5] to 4 [2; 4] (p< 0.001 in both cases). A clinically significant improvement was observed in 56% of patients in group 1 and 72% of patients in group 2. The peculiarities of the BLM dosing regimen caused higher (1.7 times) total costs than in the case of RTM. According to the CPR value, RTM showed a greater benefit (1.3 times) than BLM (954 thousand rubles versus 1.25 million rubles). The incremental cost-effectiveness ratio (ICER) was 1.4 million rubles, which does not exceed the threshold of willingness to pay for a domestic patient.Conclusion. When comparing BLM and RTM therapy for SLE patients in real-life clinical practice, greater clinical and economic efficiency was demonstrated for RTM. BLM therapy was found to be “cost-effective”.

Real-world safety profile of zanubrutinib: a disproportionality analysis based on the FAERS database

ObjectiveZanubrutinib is a second-generation Bruton’s tyrosine kinase inhibitor that has been approved for the treatment of several B cell malignancies. The aim of this study was to evaluate adverse events...

Treatment Resistant DPPX Antibody Associated Encephalitis With an Excellent Response to Combination Therapy of Rituximab and Monthly IVIG

Treatment Resistant DPPX Antibody Associated Encephalitis With an Excellent Response to Combination Therapy of Rituximab and Monthly IVIG

Herpes zoster development in living kidney transplant recipients receiving low-dose rituximab.

We evaluated whether a history of low-dose rituximab treatment affected herpes zoster development after living kidney transplantation. We enrolled 103 living kidney transplant recipients. Patients were divided into two groups according to their history of rituximab treatment; rituximab was administered to 50 living kidney transplant recipients. We assessed the difference in herpes zoster events between the two groups and determined the risk factors for herpes zoster using multivariate regression analysis. The total dose of rituximab in each kidney transplant recipient who received rituximab therapy was 200-400 mg. The rate of herpes zoster events after transplantation in recipients who received rituximab therapy (4 of 50, 8%) was not higher than that in recipients who did not receive rituximab (9 of 53, 17%) (p = 0.238). Herpes zoster-free survival did not significantly differ between the two groups (p = 0.409). In the multivariate regression analysis, the association between varicella zoster vaccination before transplantation and herpes zoster events after transplantation was confirmed, whereas rituximab therapy was not associated with herpes zoster events. Low-dose rituximab therapy in kidney transplant recipients did not influence herpes zoster development after transplantation. Varicella zoster vaccination before transplantation may play an important role in preventing herpes zoster after transplantation.

Prevention of post-transplant lymphoproliferative disorder in pediatric kidney transplant recipients.

Post-transplant lymphoproliferative disorder (PTLD) is a devastating complication of immunosuppressive treatment in both solid organ transplantations (SOT) and hematopoietic stem cell transplantations (HSCT). Epstein-Barr virus (EBV) infection precedes PTLD in 90% of patients. Rituximab, a monoclonal anti-CD20 antibody, depletes B-lymphocytes, which are the ultimate reservoir for EBV. Although rituximab therapy is commonly used as a preventive measure for PTLD in high-risk HSCT, it is not established in SOT. Pediatric kidney transplant recipients (PKTR) underwent routine EBV-PCR surveillance. Patients with increasing viral loads, despite immunosuppressive dose reduction, were managed with preventive rituximab therapy. Between 2012 and 2023, we identified eight episodes of asymptomatic EBV-PCR-positive blood tests in seven out of 65 PKTR (11%) under our care. EBV DNAemia emerged 120-720days post-transplantation. Five of seven patients with EBV DNAemia (71%) were EBV-seronegative prior to transplantation. All five patients did not respond to MMF dose reduction and were therefore treated with preventive rituximab therapy. Following this treatment, EBV PCR clearance was observed in all patients with only minimal complications. PKTR who are EBV-naïve prior to transplantation are expected to have a higher prevalence of EBV DNAemia. We found that PKTR who were EBV seronegative prior to transplantation were less likely to achieve EBV clearance in response to immunosuppression dose reduction. We suggest that rituximab therapy in PKTR may be safe and effective in EBV clearance and PTLD prevention.

The Effectiveness of Rituximab in the Treatment of Refractory Manifestations of Patients with Systematic Lupus Erythematous: A Retrospective Study

Background: Rituximab (RTX) is a chimeric antibody that directly targets B cells, which has been suggested as a new treatment option for systemic lupus erythematosus (SLE) resistant to conventional treatments. Objectives: This retrospective study aimed to investigate RTX's effect on treating SLE patients with refractory manifestations. Methods: This study was conducted on SLE patients who were resistant to treatment. The patients demographic characteristics and clinical information were collected from their medical records, and the results were compared before and after RTX therapy. Data were analyzed using SPSS software, and the significance level was less than 0.05 (P < 0.05). Results: Nephritis (26.3%), cutaneous manifestations (23.7%), and arthritis, occasionally secondary to overlap with rheumatoid arthritis (18.4%), were the most common complications that made patients (n = 55) candidates for the RTX biosimilar (Zytax). Ten patients were excluded due to a lack of complete data, and seven patients died immediately after starting Zytax due to disease severity and complications. Improvement in arthritis and cutaneous complications was reported after RTX injection in 57.1% and 44.4% of patients, respectively. Creatinine levels decreased significantly in patients with lupus nephritis after RTX injection compared to before treatment (P = 0.006). Moreover, anti-DNA was significantly different before and after RTX injection (Z = -2.89, P = 0.004). Comparison of C3 (t = 0.63; P = 0.53) and C4 (t = 1.72, P = 0.101) levels before and after RTX injection showed no significant differences. Conclusions: Based on the results, RTX improved nephritis, arthritis, and cutaneous complications in lupus patients.

7229 A Rare Case of Igg4 Hypophysitis Presenting as Hypogonadotropic Hypogonadism

Abstract Disclosure: C. Dimech: None. G. Jaiswal: None. Hypophysitis is a rare pituitary disorder including a broad range of inflammatory processes which affect the pituitary gland and infundibulum. Previously reported as 1 per 9 million individuals, the true incidence of hypophysitis per year is largely unknown due to the increase of novel etiologies such as immunoglobulin G4 (IgG4)- related disease. IgG4-related hypophysitis (IgG4-RH) was first clinically described in 2004 and later biopsy proven in 2007. The main clinical features are elevated serum IgG4 level and IgG4-positive lymphocyte infiltration of tissues on histopathology. IgG4-RH is reported to account for 1.3% of primary hypophysitis with 3.2:1 incidence ratio of men to women, in the 6th decade of life. Here we present a case of a 68-year-old Caucasian male who presented for evaluation of hypogonadotropic hypogonadism. As fasting morning testosterone levels were significantly low, MRI pituitary was completed which revealed a homogenously enhancing pituitary gland with thickened, nodular enhancement of the pituitary infundibulum. Subsequent lab work-up revealed normal function of remaining anterior pituitary without evidence of central vasopressin deficiency. Evaluation of underlying etiologies was unremarkable except for significantly elevated IgG4 levels (472mg/dL). Based on the significantly elevated IgG-4 levels (>135 mg/dl) and the radiographic findings of the pituitary infundibulum, the diagnosis of possible IgG4-RH was made. The patient was initiated on treatment with rituximab and glucocorticoid therapy with prednisone. Following 3 months of medical therapy, MRI pituitary showed resolution of stalk inflammation, confirming diagnosis of IgG4- RH. Presentation: 6/1/2024

An international, multi-center study evaluated rituximab therapy in childhood steroid-resistant nephrotic syndrome

The efficacy and safety of rituximab in childhood steroid-resistant nephrotic syndrome (SRNS) remains unclear. Therefore, we conducted a retrospective cohort study at 28 pediatric nephrology centers from 19 countries in Asia, Europe, North America and Oceania to evaluate this. Children with SRNS treated with rituximab were analyzed according to the duration of calcineurin inhibitors (CNIs) treatment before rituximab [6 months or more (CNI-resistant) and under 6 months]. Primary outcome was complete/partial remission (CR/PR) as defined by IPNA/KDIGO guidelines. Secondary outcomes included kidney failure and adverse events. Two-hundred-forty-six children (mean age, 6.9 years; 136 boys; 57% focal segmental glomerulosclerosis, FSGS) were followed a median of 32.4 months after rituximab. All patients were in non-remission before rituximab. (146 and 100 children received CNIs for 6 month or more or under 6 months before rituximab, respectively). In patients with CNI-resistant SRNS, the remission rates (CR/PR) at 3-, 6-, 12- and 24-months were 26% (95% confidence interval 19.3-34.1), 35.6% (28.0-44.0), 35.1% (27.2-43.8) and 39.1% (29.2-49.9), respectively. Twenty-five patients were in PR at 12-months, of which 22 had over 50% reduction in proteinuria from baseline. The remission rates among children treated with CNIs under 6 months before rituximab were 42% (32.3-52.3), 52% (41.8-62.0), 54% (44.3-64.5) and 60% (47.6-71.3) at 3-, 6-, 12-, and 24-months. Upon Kaplan-Meier analysis, non-remission and PR at 12-months after rituximab, compared to CR, were associated with significantly worse kidney survival Adverse events occurred in 30.5% and most were mild. Thus, rituximab enhances remission in a subset of children with SRNS, is generally safe and CR following rituximab is associated with favorable kidney outcome.

Efficacy of Pneumocystis jirovecii Pneumonia Prophylaxis in Preventing Infections among Patients with Kidney Disease Receiving Rituximab Therapy

Efficacy of Pneumocystis jirovecii Pneumonia Prophylaxis in Preventing Infections among Patients with Kidney Disease Receiving Rituximab Therapy

The indications and safety of rituximab for the treatment of pediatric autoimmune diseases: a single-center retrospective study.

Autoimmune diseases in children pose therapeutic challenges due to their refractory nature and the associated morbidity. Rituximab (RTX), a monoclonal antibody targeting CD20, has emerged as a promising steroid-sparing therapy for various autoimmune disorders by depleting B cells. However, its indications and safety in pediatric populations in our region remain insufficiently studied. This study aims to review the indications and safety of RTX in treating pediatric autoimmune diseases within a single-center setting. A retrospective study was conducted on pediatric patients aged 18 years or younger who received RTX for different autoimmune diseases between January 2013 and March 2023 at King Abdulaziz University Hospital, Saudi Arabia. Data on demographics, indications, infusion details, adverse events, and concurrent medications were collected and analyzed. Twenty-two patients were included, with nephrotic syndrome and systemic lupus erythematosus (SLE) being the most common indications for RTX. The mean age at diagnosis and first RTX infusion was 8 and 9 years, respectively. The most commonly used protocol involved administering 2 infusions of 375 mg/m2 each, given 2 weeks apart. RTX was commonly used as a second-line treatment following corticosteroids. Infusion-related adverse events occurred in 31.8% of patients, ranging from mild reactions such as chest tightness, fever, and headache to severe reactions such as anaphylaxis. No infectious related adverse events were observed. This study highlights both the varied indications for which RTX was prescribed and the need for vigilance concerning infusion-related adverse events. It underscores the importance of close monitoring and appropriate management to ensure the safety of RTX therapy in pediatric patients. Further research is warranted to optimize treatment strategies and enhance patient outcomes in this population.

Efficacy of Rituximab in Autoimmune-Mediated IgG4 Pancreaticobiliary Disease: A Systematic Review and Meta-Analysis.

IgG4 pancreaticobilliary disease (IgG4-PBD) typically shows a rapid improvement with glucocorticoid treatment, yet most patients experience a recurrence. Rituximab (RTX) has emerged as a hopeful approach to prevent relapses in IgG4-PBD. Nevertheless, there is a lack of data on the efficacy and safety of RTX in IgG4-PBD. In this study, we aim to perform a systematic review and meta-analysis to study the pooled efficacy of RTX in this patient population. Multiple databases, including MEDLINE, SCOPUS, and Embase, were searched (in March 2024) using specific terms for studies evaluating the efficacy and safety of RTX in IgG4 pancreatic biliary disease. Outcomes of interest were relapse, remission, partial remission rates, and adverse events. Standard meta-analysis methods were used using the random-effects model. I2% heterogeneity was used to assess the heterogeneity. Twelve studies were included in the study (257 patients). The pooled rate of complete remission was 68% (54% to 80%), I2 =53%, respectively. The pooled relapse rate was 23% (13% to 36%), I2=64%. The pooled rate of total adverse events was 21% (12% to 35%), I2=52%. The pooled partial remission rate is 16% (7% to 32%), I2=25%. The pooled rate of complete and partial remission was 81% (66% to 90%), I2=75%. The pooled infusion reaction and infection were 12% (7% to 18%), I2=0% and 14% (8% to 22%), I2=16%, respectively. RTX therapy appears effective in inducing and maintaining remission of pancreaticobiliary disease with a low rate of side effects. RTX presents as a promising treatment option for patients grappling with recurrent or unresponsive IgG4-related ailments. In addition, RTX emerges as an attractive alternative for individuals intolerant to steroids or experiencing IgG4-related disease relapses. Future studies comparing RTX with other immunomodulators will offer deeper insights into relapse factors and elucidate the appropriateness of utilizing this maintenance treatment following the initial flare.

Two Decades Rituximab Therapy in Anti-Neutrophil Cytoplasmic Antibody Associated Vasculitis.

Remission failure and relapse numerate as one of the main problems in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAVs). The need for new agents that provide effective and safe induction accompanied by sustained remission seems to be urgent in clinical care. The efficacy and safety of rituximab (RTX) for AAVs therapy has been reported in various studies. RTX therapy offers several advantages to treating AAVs patients compared to other therapeutic approaches including reduction of Glucocorticoids (GCs) and conventional Immunosuppressive therapy (IST) usage during both the induction of remission and maintenance phases. This reduction can lead to a lower rate of serious complications making RTX therapy a safer option. It seems that RTX may provide improved clinical outcomes in these patients mediated via B-lymphocyte depletion, Proteinase 3-antineutrophilic cytoplasmic antibody (PR3-ANCA), and myeloperoxidase-antineutrophilic cytoplasmic antibody (MPO-ANCA) titers reduction. In this regard, some uncertainties have been reported to validate the association between such depletion and clinical improvement, as suggested by other sources of autoreactive B cells that did not target with RTX. Due to the prolonged B cell depletion, fixed intervals and adjusted dosage of RTX may be required in patients with AAVs. In this narrative review, we aimed to insight better understand regarding the efficacy of RTX for effective induction and sustained remission in patients with AAVs. It seems that discovering new biomarkers predicting relapse in AAVs patients can lead to future targeted therapy.

Immunogenicity of Pneumococcal Polysaccharide Vaccine in patients with rheumatoid arthritis

The presented review searched for articles in the databases PubMed, Web of Science, Scopus, Google Scholar, eLibrary (2002-2022) and assessed the immunogenicity of the 23-valent polysaccharide pneumococcal vaccine (PPV23) in adult patients with rheumatoid arthritis (RA), receiving various antirheumatic drugs. The results of this review indicated sufficient immunogenicity of PPV23 in RA patients receiving monotherapy with various biological drugs (bDMARDs) (TNFα inhibitors, IL6 receptor inhibitors, T-lymphocyte costimulation blockers), targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), and glucocorticoids (GC) in medium and low doses. Monotherapy with methotrexate (MTX), rituximab and combination therapy with bDMARDs +MTX, tsDMARDs+MTX in RA patients reduced the postvaccination pneumococcal response. IgG AT generated in response to PPV23 injection shown functional activity even in RA patients whose antibodies were either lowered in patients receiving MTX or were not detectable at protective values following bDMARD therapy. The potential for pneumococcus antibody production in RA patients receiving therapy with disease-modifying antirheumatic drugs (DMARDs), tsDMARDs and bDMARDs, was concluded. Vaccination against pneumococcal infection should be advised prior to starting therapy due to the likelihood of low antibody levels developing during rituximab treatment.