Országos Reumatológiai és Fizioterápiás Intézet

ObjectivesDARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.MethodsEligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol. Patients received filgotinib 200 mg/day, except 15 men who received filgotinib 100 mg/day. The primary endpoints were safety and tolerability, which were assessed by the incidence of treatment-emergent adverse events (TEAEs). Safety and efficacy analyses included all enrolled patients who received ≥1 dose of filgotinib in DARWIN 3.Results739 patients entered the LTE. The total patient-years of exposure (PYE) to filgotinib was 3706.3 years; the mean exposure duration was 259.8 weeks. 497 patients (67.3%) discontinued prematurely (including 266 TEAEs and 172 withdrawals due to the patient’s decision or ‘sponsor request’). Overall exposure-adjusted incidence rate (EAIR) was 67 (95% CI 62 to 72.2)/100 PYE for TEAEs and 3.8 (95% CI 3.2 to 4.5)/100 PYE for serious TEAEs. EAIR of infections was 23.3 (95% CI 21.2 to 25.6)/100 PYE, 1.3 (95% CI 0.9 to 1.7)/100 PYE for serious infections and 1.3 (95% CI 0.9 to 1.7)/100 PYE for herpes zoster. EAIRs of major adverse cardiovascular events (0.19 (95% CI 0.8 to 0.39)/100 PYE) and malignancies (0.6 (95% CI 0.4 to 0.9)/100 PYE) were low. Disease response assessed using non-responder imputation plateaued at LTE week 12 before slowly declining over time, with overall American College of Rheumatology (ACR)20/50/70 response rates of 26.9%/20.2%/14.7% at week 396.ConclusionFilgotinib was well tolerated in patients with RA for up to 8 years. Safety and efficacy profiles were maintained in patients previously receiving either filgotinib plus methotrexate or filgotinib monotherapy.

Közleményünkben egy transzplantációra alkalmatlan korú myelomás nőbeteg kiemelkedően eredményes lenalidomid-dexamethason dublet kezeléséről számolunk be, mellyel 134 négyhetes cikluson át tudtuk myeloma multiplex betegségét remisszióban tartani. További érdekessége az esetnek, hogy a kialakult lenalidomid-rezisztenciát melphalan-prednisolon-bortezomib másodvonalbeli kezeléssel eredményesen tudtuk áttörni és a terápiát követően hosszú kezelésmentes remissziót elérni.

Malignus myopericitoma_case report_Bukovszky Bence (PBC).

In the past decade and a half, clinical diabetology has undergone enormous development. New drug classes have appeared in everyday practice (GLP1 receptor agonists, SGLT2 inhibitors), which are able to improve the outcome of cardiovascular (macrovascular) complications in diabetes within a few years or even a few months, in contrast to the drugs used in previous large, prospective studies (UKPDS, VADT). The use of thiazolidinediones (including pioglitazone) unfortunately and significantly has declined in recent years, both internationally and domestically, although tested in a randomized, controlled setting (PROactive, 2005), this drug was the first, one might say 'ahead of its time', that significantly reduced the composite clinical endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke, which became later well-known and took center stage as the 3-point MACE. In this paper, we summarize the most important evidence that accumulated with pioglitazone over the past years. We briefly overview the molecular, cellular and pathophysiological changes it causes, and then, in addition to discussing the cardiovascular, metabolic and other benefits, mention the previously suspected and now confirmed possible side effects. It is our belief that pioglitazone could be successfully used today as part of a combined treatment in properly selected patients, with due care, in the personalized treatment of type 2 diabetes. Orv Hetil. 2023; 164(26): 1012-1019.

Classical myeloproliferative diseases can be divided into Philadelphia chromosome-positive chronic myeloid leukemia and Philadelphia chromosome-negative myeloproliferative neoplasm. The driver mutations of the latter occur in the Janus kinase 2 or calreticulin genes. The coincidence of Philadelphia chromosome-negative and -positive myeloproliferative neoplasms in the same patient is exceptionally rare in the literature. During the long-term follow-up of our 120 patients with chronic myeloid leukemia, we investigated the clinical data of patients in whom Philadelphia chromosome-negative myeloproliferative disease was also confirmed. Philadelphia chromosome was detected by classical cytogenetic methods and/or fluorescence in situ hybridization. The amount of BCR-ABLI fusion RNA was monitored by quantitative real-time polymerase chain reaction. Mutations in the Janus kinase 2 and calreticulin genes were detected by quantitative allele-specific polymerase chain reaction and fragment analysis. The dynamics of disease development were inferred from the change in the amount of mutant clones over time and from the clinical data. We identified four cases carrying both Philadelphia chromosome and Janus kinase 2/calreticulin gene mutation. In some cases, competition between the clones, in other cases their co-occurrence in a common clone was observed. Isolated thrombocytosis at the time of diagnosis or persisting thrombocytosis during targeted therapy with good molecular response may call attention to the possibility of the co-occurrence of the two diseases. Co-occurrence of Philadelphia chromosome-positive and -negative myeloproliferative neoplasms is more frequent than the literature suggests. If the disease has an unusual appearance, the association of the two myeloproliferative dieseases may be suspected.

Az elmlt vekben egy j, eddig nem karakterizlt arnytalan sinuscsom-tachycardis betegcsoportot (97 beteg; 90 m-tachycardia diagnosztikus kritriumait (nyugalmi sinuscsom-frekvencia: 86,210,1/min; 24 rs Holter-monitoros EKG napi tlagos szvfrekvencia 79,95,5

Osteoarthritis (OA) as the most common joint disease is a major public health concern. To investigate the effect of multimorbidity on functional and quality of life outcomes in women with generalized osteoathritis (hand and knee arthritis, GOA). In this cross-sectional study, patients according to the American College of Rheumatology (ACR) criteria for OA were invited. The control group consisted of subjects without any musculoskeletal symptoms, osteoarthritis or inflammatory rheumatic disease. Comorbidity count was calculated from the investigated comorbidities. In the GOA group, the function was assessed by Western Ontario and McMaster Universities Arthritis Index (WOMAC), Cochin Hand Scale, Knee Injury and Osteoarthritis Outcome Score (KOOS), Health Assessment Questionnaire (HAQ), while quality of life was measured in both groups with the EuroQol-5D Scale. Interaction between summarized comorbidity count, age, body mass index (BMI) and scores were analysed. Descriptive statistics, two-sample t-test and Pearson's correlation test were used for data analysis. The study groups included 200-200 participants with a similar age spread. Significant correlation was demonstrated in both study groups between higher comorbidity count and older age (0.37, p<0.001, and 0.24, p<0.001 in the GOA and the control group, respectively) and higher BMI (0.18, p: 0.01, and 0.45, p<0.001 in the GOA and the control group, respectively). In GOA, the increasing comorbidity number had a negative effect on the measured outcomes. Age and BMI showed strong correlation with multimorbidity in both groups. The lower correlation between BMI and comorbidity count in the GOA group requires further investigation and may suggest different interactions. Orv Hetil. 2020; 161(32): 1332-1340.

Absztrakt: A myeloma multiplex első vonalbeli kezelése Magyarországon érdemben nem változott az elmúlt évizedben, alapját bortezomibbázisú tripletek és az arra alkalmasaknál nagy dózisú kemoterápiát követő autológ őssejtátültetés képezi. Közleményünkben a myeloma multiplex első vonalbeli kezelésének legújabb fejleményeit foglaljuk össze az ASH (American Society of Hematology) és az EHA (European Hematology Association) kongresszusain bejelentetett eredmények ismertetésével. Bár a smouldering myeloma (SMM) jelenleg nem kezelési indikáció, a nagy rizikójú SMM korai experimentális kezelési eredményei ígéretesek. Az újonnan diagnosztizált, transzplantációjelölt betegek első vonalbeli daratumumab- és/vagy carfilzomibbázisú indukciós kezelései kiemelkedően hatásosak, nem befolyásolják az őssejtgyűjtést, és növelik az autológ őssejtátültetéssel végzett konszolidációs terápia hatékonyságát. A bizonyítottan hatékony lenalidomidfenntartó kezelésre nem jelölt betegek számára az ixazomibfenntartó kezelés már evidencián alapulhat. Nem transzplantábilis myelomás betegeink számára az első vonalbeli daratumumabbázisú kezelés több kombinációban is mély és tartós választ biztosíthat. Esendő betegeink lenalidomid-dexamethason első vonalbeli kezeléséből eredményes indukciót követően a szteroid káros következmények nélkül elhagyható, az elért eredményt a lenalidomid monoterápia fenntarthatja.