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Disease remission and sustained halting of radiographic progression with combination etanercept and methotrexate in patients with rheumatoid arthritis

van der Heijde, D; Klareskog, L; Landewe, R; Bruyn, G A W; Cantagrel, A; Durez, P; Herrero-Beaumont, G; Molad, Y; Codreanu, C; Valentini, G; Zahora, R; Pedersen, R; MacPeek, D; Wajdula, J; Fatenejad, S
OBJECTIVE: The Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) is a 3-year, double-blind, multicenter study evaluating the efficacy and safety of etanercept, methotrexate, and the combination of etanercept plus methotrexate in patients with active rheumatoid arthritis (RA). The results after 1 and 2 years of the study have been previously reported. Here we provide the 3-year clinical and radiographic outcomes and safety of etanercept, methotrexate, and the combination in patients with RA. METHODS: In this randomized, double-blind, multicenter TEMPO study, 682 patients received etanercept 25 mg twice weekly, methotrexate < or =20 mg weekly, or the combination. Key efficacy assessments included the Disease Activity Score (DAS) and the DAS in 28 joints. RESULTS: Combination therapy resulted in significantly greater improvement in the DAS and in more patients with disease in remission than either monotherapy. This finding was confirmed by longitudinal analysis; patients receiving combination therapy were more than twice as likely to have disease in remission than those receiving either monotherapy. Independent predictors of remission included male sex, lower disease activity, lower level of joint destruction, and/or better physical function. Combination and etanercept therapy both resulted in significantly less radiographic progression than did methotrexate (P < 0.05). Etanercept and combination treatment were well tolerated, with no new safety findings. CONCLUSION: Etanercept plus methotrexate showed sustained efficacy through 3 years and remained more effective than either monotherapy, even after adjustment for patient withdrawal. Combination therapy for 3 years led to disease remission and inhibition of radiographic progression, 2 key goals for treatment of patients with RA.
PMID: 18050208
ISSN: 0004-3591
CID: 1458452

Soluble triggering receptor expressed on myeloid cells-1 for distinguishing bacterial from aseptic meningitis in adults

Bishara, J; Hadari, N; Shalita-Chesner, M; Samra, Z; Ofir, O; Paul, M; Peled, N; Pitlik, S; Molad, Y
The aim of the present study was to evaluate whether soluble triggering receptor expressed on myeloid cells (sTREM-1) is present in the cerebrospinal fluid (CSF) of patients with acute meningitis and if its presence can predict bacterial infection. We found elevated levels of sTREM-1 in the CSF of seven of the nine (78%) patients with culture-positive specimens and in none of 12 (0%) patients with culture-negative specimens (sensitivity: 78%; specificity: 100%). The area under the receiver operating characteristic curve for sTREM-1 in the CSF as a predictor for bacterial meningitis was 0.889. This suggests that sTREM-1 is upregulated in the CSF of patients with bacterial meningitis with high specificity and that its presence can potentially assist clinicians in the diagnosis of bacterial meningitis.
PMID: 17610097
ISSN: 0934-9723
CID: 1458462

Chronic idiopathic granulomatous mastitis [Case Report]

Katz, Uriel; Molad, Yair; Ablin, Jacob; Ben-David, Debby; Paran, Daphna; Gutman, Mordechai; Langevitz, Pnina
We describe four women with idiopathic granulomatous mastitis, a rare benign disease. Age range was 32-40 years. Disease duration was less than 1 year in three patients and long term in the fourth. The diagnosis was based on histological findings, after extensive workup ruled out malignancy and known causes of granulomatous mastitis. Treatment with prednisone with gradual tapering yielded a good response. Clinicians should consider the possibility of idiopathic granulomatous mastitis in young women with inflammatory breast processes and negative findings on relevant biopsy, laboratory, and imaging studies. Glucocorticoids are the treatment of choice; surgery is not recommended. Some patients require a glucocorticoid-sparing drug.
PMID: 17894025
ISSN: 0077-8923
CID: 1458312

Systemic and ocular manifestations of catastrophic antiphospholipid syndrome: a case report

Bahar, Irit; Hershcovici, Tiberiu; Axer-Siegel, Ruth; Molad, Yair; Weinberger, Dov; Kramer, Michal
PMID: 25390222
ISSN: 1935-1089
CID: 1458322

Neutrophils (Polymorphonuclear Leukocytes) in Systemic Lupus Erythematosus

Chapter by: Molad, Y; Cronstein, B
in: Systemic Lupus Erythematosus by Tsokos, George C; Gordon, Caroline; Smolen, Josef S. [Eds]
Philadelphia : Mosby Elsevier, c2007
pp. 281-286
ISBN: 0323044344
CID: 644372

Systemic lupus erythematosus and pregnancy

Molad, Yair
PURPOSE OF REVIEW: Pregnancy in patients with systemic lupus erythematosus is associated with a high risk of maternal disease exacerbation and adverse fetal outcome. This review summarizes recent published findings on lupus pregnancy. RECENT FINDINGS: The literature is in agreement that for most women with inactive and stable systemic lupus erythematosus, pregnancy is safe for both mother and fetus. The main risk factors for adverse pregnancy course and outcome are active disease, nephritis with proteinuria, hypertension, and maternal serum antibodies to SS-A/Ro, SS-B/La, cardiolipin, beta2-glycoprotein I, and lupus anticoagulant. Recent studies have broadened our understanding of the immunological mechanism underlying congenital heart block induced by anti-Ro/La antibodies. In addition, the approach to oral contraceptives has been modified on the basis of two well controlled studies suggesting that they do not cause exacerbation of inactive or mild disease. SUMMARY: Pregnancy in patients with systemic lupus erythematosus is safe and manageable provided the disease is stable. Patients should be evaluated before pregnancy for pregestational risk factors and be closely followed during pregnancy. In most cases of lupus flare during pregnancy, the disease can be safely managed.
PMID: 17099331
ISSN: 1040-872x
CID: 1458332

Spontaneous retroperitoneal bleeding from renal microaneurysms and pancreatic pseudocyst in a patient with systemic lupus erythematosus [Case Report]

Melamed, N; Molad, Y
Visceral vasculitis and pancreatic pseudocyst are rare manifestations of systemic lupus erythematosus (SLE). We describe a patient with SLE who presented with spontaneous bilateral perinephric and retroperitoneal haematoma secondary to polyarteritis nodosa (PAN)-like vasculitis of the renal arteries, which subsequently evolved into systemic vasculitis with pancreatic pseudocyst formation.
PMID: 17343259
ISSN: 0300-9742
CID: 1458472

Heart valve calcification in young patients with systemic lupus erythematosus: a window to premature atherosclerotic vascular morbidity and a risk factor for all-cause mortality

Molad, Yair; Levin-Iaina, Nomi; Vaturi, Mordehay; Sulkes, Jaqueline; Sagie, Alex
The objective of the study was to evaluate the association between heart valve calcification and atherosclerosis and outcome in systemic lupus erythematosus (SLE). One-hundred and seven patients with SLE (mean age 45.9 +/- 14.7 years) were studied by 2D transthoracic echocardiography. Mitral annulus calcification (MAC) was detected in 24 patients (22.6%) and aortic valve calcification (AVC) in 22 (20.1%). Both MAC and AVC were associated with older age (r = 0.2, p = 0.02; r = 0.40, p
PMID: 16046220
ISSN: 0021-9150
CID: 1458342

Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A3 adenosine receptor expression

Ochaion, Avivit; Bar-Yehuda, Sara; Cohn, Shira; Del Valle, Luis; Perez-Liz, Georginia; Madi, Lea; Barer, Faina; Farbstein, Motti; Fishman-Furman, Sari; Reitblat, Tatiana; Reitblat, Alexander; Amital, Howard; Levi, Yair; Molad, Yair; Mader, Reuven; Tishler, Moshe; Langevitz, Pnina; Zabutti, Alexander; Fishman, Pnina
Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A3 adenosine receptor (A3AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A3AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A3AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A3AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A3AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A3AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A2AAR and A3AR over-expression in paw cells from treated animals. Moreover, increased A3AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A3AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A3AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA.
PMCID:1794513
PMID: 17101059
ISSN: 1478-6354
CID: 1458352

Maternal and fetal outcome of lupus pregnancy: a prospective study of 29 pregnancies

Molad, Y; Borkowski, T; Monselise, A; Ben-Haroush, A; Sulkes, J; Hod, M; Feldberg, D; Bar, J
The aim of this study was to analyse pregestational and pregnancy risk factors for adverse fetal and maternal outcome in lupus pregnancy. Twenty women with systemic lupus erythematosus (SLE) (29 pregnancies) were prospectively evaluated. Mean patient age was 29.5+/-4.7 years, and mean disease duration, 6.3+/-6.5 years. Twenty-two pregnancies (75.9%) ended in live births; preterm delivery occurred in 17.4%, intrauterine growth restriction in 50%, preeclampsia in 3.7%, and gestational hypertension in 8%. Six pregnancies (20.7%) ended in spontaneous abortions. Adverse live-birth outcome was significantly associated with low pregestational serum albumin level, elevated gestational anti-dsDNA antibody, and diabetes mellitus. Spontaneous abortion was directly associated with low levels of pregestational serum albumin, positive anticardiolipin IgA, anti-beta2-glycoprotein I IgM, and anti-La antibodies, and inversely associated with number of patients' children. Postgestational lupus flare-up was noted in six pregnancies. Risk factors included high pregestational SLE Disease Activity Index (SLEDAI), lower serum albumin, elevated serum antibody to dsDNA, proteinuria, and use of prednisone and hydroxychloroquine. We conclude that despite high rate of obstetrical complications and postpartum lupus flare-up, pregnancy poses low risk for the majority of women with SLE.
PMID: 15751819
ISSN: 0961-2033
CID: 1458482