Co-present rheumatoid arthritis and gout successfully treated with abatacept

Puszczewicz, Mariusz; Ociepa-Zawal, Marta

doi:10.1007/s10067-008-1030-x

Cited by 8 publications

(6 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In PMF, CALR-mutated patients were also younger and presented with higher platelet count, better risk profile, and lower frequencies of anemia, leukocytosis, and spliceosome mutations [13]. MPL mutations have been inconsistently [30] associated with older age, female gender, lower hemoglobin level, and higher platelet count [16,31,32], no associations with survival or leukemic transformation have been reported [16,31].…”

mentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

2015

View full text Add to dashboard Cite

Disease overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms, respectively characterized by erythrocytosis and thrombocytosis. Other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation. Diagnosis: PV is defined by a JAK2 mutation, whose absence, combined with normal or increased serum erythropoietin level, makes the diagnosis unlikely. Differential diagnosis in ET includes reactive thrombocytosis, chronic myeloid leukemia, and prefibrotic myelofibrosis. Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus oncogene (MPL) mutations occur in approximately 55%, 25%, and 3% of ET patients, respectively. The same molecular markers are also present in prefibrotic myelofibrosis, which needs to be morphologically distinguished from ET. Survival and leukemic/fibrotic transformation: Median survivals are ∼14 years for PV and 20 years for ET; the corresponding values for younger patients are 24 and 33 years. Life‐expectancy in ET is inferior to the control population. JAK2/CALR mutational status does not affect survival in ET. Risk factors for survival in ET and PV include advanced age, leukocytosis, and thrombosis. Leukemic transformation rates at 20 years are estimated at <10% for PV and 5% for ET; fibrotic transformation rates are slightly higher. Thrombosis risk stratification: Current risk stratification in PV and ET is designed to estimate the likelihood of recurrent thrombosis: high‐risk is defined by the presence of age >60 years or presence of thrombosis history; low‐risk is defined by the absence of both of these two risk factors. Recent data consider JAK2V617F and cardiovascular risk factors as additional risk factors. Presence of extreme thrombocytosis might be associated with acquired von Willebrand syndrome (AvWS) and, therefore, risk of bleeding. Risk‐adapted therapy: The main goal of therapy in PV and ET is to prevent thrombohemorrhagic complications. In low risk patients, this is accomplished by the use of low‐dose aspirin and phlebotomy (hematocrit target <45%) in PV. In high risk (for thrombosis) patients, treatment with hydroxyurea is additionally recommended. Treatment with busulfan or interferon‐α is usually effective in hydroxyurea failures and the additional value of JAK inhibitor therapy in such cases is limited. Screening for AvWS is recommended before administrating aspirin, in the presence of extreme thrombocytosis. Am. J. Hematol. 90:163–173, 2015. © 2014 Wiley Periodicals, Inc.

show abstract

mentioning

confidence: 99%

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

2015

View full text Add to dashboard Cite

show abstract

“…Therefore, different arthritis types subtend persistent activation of both common and different T cell subsets, and studying ZETA down‐regulation may help distinguish seronegative RA from non‐RA forms. In this regard, a major role for CD4 + CD28 + in SF of non‐RA patients, counterposed to the major role of CD8 + CD28null in SF of seronegative RA patients, may account for the good outcomes observed following treatment with the CD28/B7 modulator abatacept in PsA and even in gout patients, but not in seronegative RA . Moreover, while high titers of autoantibodies would predict a more aggressive disease in seropositive patients , measuring ZETA expression in SF T cells may be particularly useful for predicting arthritis severity in seronegative patients.…”

Section: Discussionmentioning

confidence: 99%

Measuring the T‐cell down‐regulation of TCR‐zeta, ZAP‐70 and CD28 in arthritis patients: An old tool for new biomarkers

et al. 2019

View full text Add to dashboard Cite

Low T-cell receptor (TCR)/CD28 signaling lymphocytes are expanded in arthritis. We asked whether the down-expression of TCR-related molecules correlates with specific arthritis characteristics and if it has clinical implications. TCR-ZETA, ZAP-70 and CD28 expression was measured by flow cytometry in synovial fluid (SF) and peripheral blood (PB)-derived T cells. In PB, ZETA-downregulation in CD4 + CD28 + and consequent CD4 + CD28lowZETAlow cell expansion correlate with CRP elevation, leukocyte recruitment into SF and, primarily, disease activity (DAS). In some patients, ZETA-downregulation extends to CD8 + CD28null and/or CD8 + CD28 + cells, and this correlates with enhanced leukocyte recruitment, multiple joint involvement, and disability index (HAQ). ZETAdownregulation in CD4 + CD28 + may also lead to CD4 + CD28 + ZETAnull cell expansion, which strongly correlates with HAQ. In SF, ZETA-downregulation in CD8 + CD28null and consequent CD8 + CD28nullZETAlow/null cell expansion correlate with CRP elevation and neutrophilic influx into SF, whereas ZAP-downregulation in CD8 + CD28 + and consequent CD8 + CD28lowZAPlow cell expansion strongly correlate with HAQ and DAS. ZETAdownregulation is preponderant in SF of seronegative arthritides, with seronegative rheumatoid arthritis showing significant down-regulation in CD8 + CD28null, and nonrheumatoid arthritides showing significant down-regulation in CD4 + CD28 + . Altogether, we identified new molecular and cellular biomarkers of arthritis-related T-cell inflammation, useful for assessing arthritis activity, predicting polyarticular progression and functional impairment, characterizing seronegative arthritides, and possibly tailoring immunotherapies.Keywords: Arthritis r CD28 r T cells r TCR/CD3-zeta chain (ZETA) r ZAP-70Additional supporting information may be found online in the Supporting Information section at the end of the article.Abbreviations: CRP: C-reactive protein · DAS: disease activity score · HAQ: health assessment questionnaire-disability index · MFI: median fluorescence intensity · non-RA: non-rheumatoid arthritis · PB: peripheral blood · RA: rheumatoid arthritis · RF: rheumatoid factor · SF: synovial fluid · ZAP (ZAP-70): TCRζ-associated protein kinase 70 · ZETA (TCRζ): T cell receptor zeta chain

show abstract

“…Another drug currently used in RA [79], abatacept, completely suppressed gout activity in a patient with a long-term history of gout and subsequent superimposed RA [80]. Finally, although in 1996 Lioté et al observed that the recombinant human and the ultrapure TGF β 1 reduced the number of attacks in an experimental model of gout [81], no further studies on this potential therapeutic approach have been performed.…”

Section: Symptoms Relievers Bio(techno)logical Drugs: Other Bio(tementioning

confidence: 99%

“…IL-6 inhibitor tocilizumab (8 mg/kg/month) completely stopped gouty attacks in a 44-year-old man with a 12-year history of severe uncontrolled tophaceous gout refractory to colchicine and diclofenac [ 78 ]. Another drug currently used in RA [ 79 ], abatacept, completely suppressed gout activity in a patient with a long-term history of gout and subsequent superimposed RA [ 80 ]. Finally, although in 1996 Lioté et al observed that the recombinant human and the ultrapure TGF β 1 reduced the number of attacks in an experimental model of gout [ 81 ], no further studies on this potential therapeutic approach have been performed.…”

Section: Symptoms Relievers Bio(techno)logical Drugs: Other Bio(tementioning

confidence: 99%

The Emerging Role of Biotechnological Drugs in the Treatment of Gout

Cavagna

Taylor

2014

BioMed Research International

View full text Add to dashboard Cite

One of the most important therapeutic advances obtained in the field of rheumatology is the availability of the so-called bio(techno)logical drugs, which have deeply changed treatment perspectives in diseases such as rheumatoid arthritis and ankylosing spondylitis. According to the steadily increasing attention on gout, due to well-established prognostic and epidemiology implications, in the last 5 years, the same change of perspective has been observed also for this disease. In fact, several bio(techno)logical agents have been investigated both for the management of the articular gout symptoms, targeting mainly interleukin-1β, as well as urate-lowering therapies such as recombinant uricases. Among the IL-1β inhibitors, the majority of studies involve drugs such as anakinra, canakinumab, and rilonacept, but other compounds are under development. Moreover, other potential targets have been suggested, as, for example, the TNF alpha and IL-6, even if data obtained are less robust than those of IL-1β inhibitors. Regarding urate-lowering therapies, the recombinant uricases pegloticase and rasburicase clearly showed their effectiveness in gout patients. Also in this case, new compounds are under development. The aim of this review is to focus on the various aspects of different bio(techno)logical drugs in gouty patients.

show abstract

Co-present rheumatoid arthritis and gout successfully treated with abatacept

Cited by 8 publications

References 1 publication

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

Polycythemia vera and essential thrombocythemia: 2015 update on diagnosis, risk‐stratification and management

Measuring the T‐cell down‐regulation of TCR‐zeta, ZAP‐70 and CD28 in arthritis patients: An old tool for new biomarkers

The Emerging Role of Biotechnological Drugs in the Treatment of Gout

Contact Info

Product

Resources

About