rituximab
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INTRODUCTION: Since 2012, when The Kidney Disease: Improving Global Outcomes (KDIGO) initiative published the first recommendations for the management and treatment of glomerular diseases, there has been enormous progress in understanding pathogenesis, identifying new diagnostic biomarkers and treating these diseases. Rituximab had become a promisisng treatment option in patients with primary glomerular disease, as confirmed by several clinical studies, where it has led to a significant reduction in proteinuria and a reduction in the incidence of relapses of the underlying disease. In this work we present our experiences with rituximab treatment. MATERIALS AND METHODS: We retrospectively analyzed 9 patients with primary glomerulopathy resistant to srandard immunosuppressive therapy who received rituximab as rescue treatment. We evaluated the effect of rituximab induction treatment on the development of quantitative proteinuria. RESULTS: By evaluating the 24-hour proteinuria before and after treatment, we demonstrated a statistically significant decrease in proteinuria in our group of patients immediately after the las dose of rituximab. We did not notice a significant change in renal function. CONCLUSION: Rituximab represents an effective alternative in the treatment of primary glomerulopathies, especially in cases of resistance to standard immunosuppressive therapy, which is shared by the clinical experience presented by us.
- Klíčová slova
- Proteinuria, primary glomerulopathy, rituximab,
- MeSH
- imunosupresiva MeSH
- lidé MeSH
- nemoci ledvin * MeSH
- proteinurie MeSH
- retrospektivní studie MeSH
- rituximab MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- imunosupresiva MeSH
- rituximab MeSH
Rheumatoid arthritis (RA) is a serious, chronic, inflammatory disorder that damages the joints. The chronic destructive process causes pain to patients with RA and leads to the development of permanent disability. At present, great emphasis is placed on timely and effective therapy for RA, which is able to halt or slow the development of the disorder. At present we do not have any means of curing RA, the main objective for treatment is to induce remission of the disorder and prevent structural damage to the joints and the development of permanent disability. The relatively frequent failure of disease modifying medications (DMARDs) lead to efforts to find new resources for the treatment of RA. So called biological medicines were recently introduced into therapeutic use. These were mainly TNFalpha blockers. Experience has shown that approximately a third of patients with RA do not respond even to treatment with such medicines. Rituximab (MabThera), a monoclonal antibody against CD20 positive B-lymphocytes, is a new biological medicine approved for RA therapy. It represents a new hope for patients with active RA, for whom earlier therapy with TNFa blockers has failed.
- MeSH
- antirevmatika farmakologie terapeutické užití MeSH
- lidé MeSH
- monoklonální protilátky farmakologie terapeutické užití MeSH
- myší monoklonální protilátky MeSH
- revmatoidní artritida farmakoterapie MeSH
- rituximab MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antirevmatika MeSH
- monoklonální protilátky MeSH
- myší monoklonální protilátky MeSH
- rituximab MeSH
Cancer treatment is based on combination of systemic chemotherapy and radiotherapy. The new methods of therapy based on biological priniciples have been introduced within last decade. The monoclonal antibody rituximab was launched ten years ago in 1997. This antibody against CD20 antigen, which is expressed on B cell lymphocytes and on the majority of B-cell lymphoid malignancies, has revolutionized the lymphoma therapeutic strategy. The immuno-chemotherapy has dramatically improved the outcome of diffuse large B-cell lymphomas patients. The combination of rituximab and chemotherapy as first line therapy has for the first time improved the survival of follicular lymphoma patients previously considered to be incurable. Rituximab has become the inevitable part of therapeutic regimens for other B-cell lymphomas, chronic lymphocytic leukaemia as well as for some non-malignant diseases. The important milestones, the therapeutic results of rituximab and other approved monoclonal antibodies (alemtuzumab, ibritumomab tiuxetan 90Y) is reviewed in this paper as well as short compendium of new antibodies is given. The cost effectiveness of the new therapy is discussed.
- MeSH
- alemtuzumab MeSH
- humanizované monoklonální protilátky MeSH
- lidé MeSH
- lymfom farmakoterapie MeSH
- monoklonální protilátky farmakologie terapeutické užití MeSH
- myší monoklonální protilátky MeSH
- protilátky nádorové farmakologie terapeutické užití MeSH
- radioimunoterapie MeSH
- radioizotopy ytria MeSH
- rituximab MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- alemtuzumab MeSH
- humanizované monoklonální protilátky MeSH
- ibritumomab tiuxetan MeSH Prohlížeč
- monoklonální protilátky MeSH
- myší monoklonální protilátky MeSH
- protilátky nádorové MeSH
- radioizotopy ytria MeSH
- rituximab MeSH
UNLABELLED: We describe the rationale and design of the ongoing randomized, active-controlled, multicenter, Phase III study evaluating the efficacy of pixantrone and rituximab versus gemcitabine and rituximab in patients with diffuse large B-cell lymphoma or follicular grade 3 lymphoma, who are ineligible for high-dose chemotherapy and stem cell transplantation, and who failed front-line regimens containing rituximab. The administration schedule is pixantrone 50 mg/m(2) intravenously (iv.) or gemcitabine 1000 mg/m(2) iv. on days 1, 8 and 15, combined with rituximab 375 mg/m(2) iv. on day 1, up to six cycles. Pixantrone has a conditional European marketing approval for monotherapy in adults with multiple relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Our trial explores the efficacy of combining pixantrone with rituximab and completes postauthorization measures. TRIAL REGISTRATION NUMBER: NCT01321541.
- Klíčová slova
- DLBCL, aggressive non-Hodgkin lymphoma, gemcitabine, pixantrone, relapse, rituximab,
- MeSH
- deoxycytidin aplikace a dávkování škodlivé účinky analogy a deriváty MeSH
- dospělí MeSH
- gemcitabin MeSH
- isochinoliny aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- nehodgkinský lymfom farmakoterapie MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- rituximab aplikace a dávkování škodlivé účinky MeSH
- senioři MeSH
- výzkumný projekt MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- deoxycytidin MeSH
- gemcitabin MeSH
- isochinoliny MeSH
- pixantrone MeSH Prohlížeč
- rituximab MeSH
IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m2, to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy.
- Klíčová slova
- IgA nephropathy, proteinuria, rituximab,
- MeSH
- dospělí MeSH
- IgA nefropatie komplikace farmakoterapie imunologie patofyziologie MeSH
- imunologické faktory terapeutické užití MeSH
- ledviny patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- proteinurie etiologie MeSH
- rituximab terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- imunologické faktory MeSH
- rituximab MeSH
Successful rituximab treatment of granulomatous/lymphocytic interstitial lung disease in common variable immunodeficiency Common variable immunodeficiency, a heterogeneous group of diseases, represents a clinically relevant form of antibody immunodeficiency. Granulomatous/lymphocytic interstitial lung disease is among the most serious complications. A case report is presented of a young women with granulomatous/lymphocytic interstitial lung disease and splenomegaly accompanied by pancytopenia. Intravenous rituximab treatment in monotherapy (at a weekly dose of 375 mg/m2 for four consecutive weeks, repeated six months later) not only led to a significant improvement in clinical symptoms but also to positive morphological and functional lung changes, mitigation of pancytopenia, considerable reduction of alkaline phosphatase level, and disappearance of splenic granulomas. The treatment was well tolerated without any side effects. The case report presented suggests possible efficacy and safety of rituximab monotherapy in patients with a complicated form of common variable immunodeficiency. KEYWORDS Rituximab - antibody immunodeficiency - lung disease - treatment Epidemiol. Mikrobiol. Imunol., 67, 2018, č. 3, s. 142-148.
- Klíčová slova
- 2018, 67, Rituximab - antibody immunodeficiency - lung disease - treatment Epidemiol. Mikrobiol. Imunol., s. 142-148, č. 3,
- MeSH
- běžná variabilní imunodeficience * komplikace MeSH
- imunologické faktory terapeutické užití MeSH
- intersticiální plicní nemoci * farmakoterapie etiologie MeSH
- lidé MeSH
- rituximab * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- imunologické faktory MeSH
- rituximab * MeSH
OBJECTIVE: To compare the effectiveness of biologics after rituximab (RTX) treatment in RA. METHODS: The effectiveness of TNF-α inhibitors (TNFi), abatacept (ABA) or tocilizumab (TCZ) was examined in patients previously treated with RTX using clinical data collected in the Collaborative Registries for the Evaluation of Rituximab in RA Collaborative registry. Patients had stopped RTX 6 months or less prior to the new biologic and had a baseline visit within 21 days of starting the new biologic. RESULTS: Two hundred and sixty-five patients were analysed after 6 months of treatment. Patients on TCZ (n = 86) had a greater decline of DAS28-ESR and clinical disease activity index than patients on TNFi (n = 89) or ABA (n = 90). This effect was also seen after adjusting for baseline prednisone use and the number of previous biologics. The mean DAS28-ESR scores in patients on TCZ were 1.0 (95% CI: 0.2, 1.7) and 1.8 (95% CI: 1.0, 2.5) points lower than in patients on TNFi or ABA, respectively. In patients on TCZ, the clinical disease activity index was 9.4 (95% CI: 1.7, 16.1) and 8.1 (95% CI: 0.9, 15.3) points lower than on TNFi and ABA, respectively. Patients on TCZ more frequently had good EULAR responses than patients on TNFi or ABA (66 vs 31 vs 14%, P < 0.001). The HAQ disability index improved in all treatment groups (P < 0.001), but did not differ between biologics, as did drug retention rates. The reasons for discontinuation of RTX and the number of previous biologics had no influence on outcomes. CONCLUSION: In this observational cohort of patients who discontinued RTX, TCZ provided a better control of RA than ABA or TNFi.
- Klíčová slova
- biologic drugs, disease activity, rheumatoid arthritis, rituximab, tocilizumab,
- MeSH
- antirevmatika terapeutické užití MeSH
- časové faktory MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- registrace * MeSH
- revmatoidní artritida farmakoterapie MeSH
- rituximab terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- antirevmatika MeSH
- rituximab MeSH
BACKGROUND: Despite recent advances in the treatment of aggressive lymphomas, a significant fraction of patients still succumbs to their disease. Thus, novel therapies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects. METHODS: Antibody single and combination efficacy was determined investigating different modes of action including direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in in vitro and in vivo models of aggressive B-cell lymphoma comprising diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). RESULTS: Three different sensitivity profiles to antibody monotherapy or combination treatment were observed in in vitro models: while 1/11 cell lines was primarily sensitive to tafasitamab and 2/11 to rituximab, the combination resulted in enhanced cell death in 8/11 cell lines in at least one mode of action. Treatment with either antibody or the combination resulted in decreased expression of the oncogenic transcription factor MYC and inhibition of AKT signaling, which mirrored the cell line-specific sensitivities to direct cytotoxicity. At last, the combination resulted in a synergistic survival benefit in a PBMC-humanized Ramos NOD/SCID mouse model. CONCLUSION: This study demonstrates that the combination of tafasitamab and rituximab improves efficacy compared to single-agent treatments in models of aggressive B-cell lymphoma in vitro and in vivo.
- Klíčová slova
- CD19, CD20, antibody therapy, lymphoma, rituximab, tafasitamab, tumor immunology,
- MeSH
- Burkittův lymfom * farmakoterapie MeSH
- difúzní velkobuněčný B-lymfom * farmakoterapie MeSH
- humanizované monoklonální protilátky MeSH
- leukocyty mononukleární MeSH
- myši inbrední NOD MeSH
- myši SCID MeSH
- myši MeSH
- rituximab farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- humanizované monoklonální protilátky MeSH
- rituximab MeSH
- tafasitamab MeSH Prohlížeč
BACKGROUND: Idiopathic retroperitoneal fibrosis is characterized by the development of inflammatory infiltrates with marked fibrosis along the large retroperitoneal vessels. Rituximab in combination with glucocorticoids constitute an effective therapy, but the responses are not long-lasting. In other similar situations, addition of cyclophosphamide to the combination achieved longer and deeper responses. This was the reason to use the triple combination in this case. CASE: A 56-year-old man came with four weeks lasting abdominal pain with CT finding of retroperitoneal fibrosis with unilateral ureteral occlusion. Biopsy confirmed retroperitoneal fibrosis with histological findings of IgG4-associated disease. Treatment with prednizone was poorly tolerated. Therefore, the patient was switched to the combination of rituximab 375 mg/m2 on day 1, cyclophosphamide 300 mg/m2 in infusion in days 1 and 15, plus dexamethasone 20 mg in infusion on days 1 and 15, repeated in a 28-day cycle. RESULTS: Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) examination after 4 months of treatment showed a marked decrease in FDG accumulation and complete disappearance of the fibrotic mass. After 8 months, the induction therapy was followed by maintenance therapy with rituximab 1,000 mg plus dexamethasone 20 mg in 6-month intervals. Control PET/MR examination after 3 years is consistent with complete remission. The number of circulating plasmablasts correlated with the disease activity. CONCLUSION: Treatment of retroperitoneal fibrosis with the tripple combination of rituximab, cyclophosphamide and dexamethasone achieved a very rapid disappearance of pathological FDG accumulation and fibrotic retroperitoneal mass, with complete disappearance achieved after 4 months of treatment. After 3 years of maitenance therapy, the diesease is still in complete remission on PET/MR examination. We suggest to continue the maintenance therapy with rituximab because of some increase in the number of circulating plasmablasts after prolongation of the intervals between rituximab administration.
- Klíčová slova
- Cyclophosphamide, IgG4-related disease, circulating plasmablasts, cyclophosphamide, retroperitoneal fibrosis, rituximab,
- MeSH
- cyklofosfamid * terapeutické užití aplikace a dávkování MeSH
- dexamethason * terapeutické užití aplikace a dávkování MeSH
- fluorodeoxyglukosa F18 * MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- PET/CT MeSH
- retroperitoneální fibróza * farmakoterapie diagnostické zobrazování MeSH
- rituximab * terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- cyklofosfamid * MeSH
- dexamethason * MeSH
- fluorodeoxyglukosa F18 * MeSH
- rituximab * MeSH
- Klíčová slova
- ANCA, glomerulonephritis, rituximab,
- MeSH
- ANCA-asociované vaskulitidy * farmakoterapie komplikace MeSH
- glomerulonefritida * komplikace MeSH
- křehký senior MeSH
- ledviny MeSH
- lidé MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- rituximab terapeutické užití MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- protilátky proti cytoplazmě neutrofilů MeSH
- rituximab MeSH