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MMF and interstitial lung disease

Elizabeth R Volkmann, Donald P Tashkin, Michael D Roth, Philip J Clements, Dinesh Khanna, Daniel E Furst, Maureen Mayes, Julio Charles, Chi-Hong Tseng, Robert M Elashoff, Shervin Assassi
BACKGROUND: Increased circulatory levels of the chemokine CXCL4 have been associated with the presence of interstitial lung disease (ILD) in an observational study of patients with systemic sclerosis (SSc). The purpose of the present study was to evaluate the relationship between baseline CXCL4 level and extent of ILD in the context of a randomized controlled trial and to determine whether changes in CXCL4 levels in response to immunosuppression are associated with future progression of SSc-ILD...
December 30, 2016: Arthritis Research & Therapy
Donald P Tashkin, Elizabeth R Volkmann, Chi-Hong Tseng, Michael D Roth, Dinesh Khanna, Daniel E Furst, Philip J Clements, Arthur Theodore, Suzanne Kafaja, Grace Hyun Kim, Jonathan Goldin, Edgar Ariolla, Robert M Elashoff
BACKGROUND: Cough is a common symptom of scleroderma-related interstitial lung disease (SSc-ILD), but its relationship to other characteristics of SSc-ILD, impact on cough-specific QoL and response to therapy for SSc-ILD have not been well studied. METHODS: We investigated frequent cough (FC) in SSc-ILD patients (N=142) enrolled in Scleroderma Lung Study II, a randomized controlled trial comparing mycophenolate mofetil (MMF) and oral cyclophosphamide (CYC) as treatments for ILD...
December 22, 2016: Chest
Julie Morisset, Kerri A Johannson, Eric Vittinghoff, Carlos Aravena, Brett M Elicker, Kirk D Jones, Charlene D Fell, Helene Manganas, Bruno-Pierre Dubé, Paul J Wolters, Harold R Collard, Christopher J Ryerson, Brett Ley
BACKGROUND: The treatment of chronic hypersensitivity pneumonitis (cHP) often includes systemic oral corticosteroids, but the optimal pharmacologic management remains unclear. The morbidity associated with prednisone has motivated the search for alternative therapies. We aimed to determine the effect of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA) on lung function in patients with cHP. METHODS: Patients with cHP treated with either MMF or AZA were retrospectively identified from four interstitial lung disease centers...
November 2, 2016: Chest
Dinesh Khanna, Carlo Albera, Aryeh Fischer, Nader Khalidi, Ganesh Raghu, Lorinda Chung, Dan Chen, Elena Schiopu, Margit Tagliaferri, James R Seibold, Eduard Gorina
OBJECTIVE: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) shares a number of clinical features and pathogenic mechanisms with idiopathic pulmonary fibrosis (IPF). This study was designed to evaluate the tolerability of the IPF treatment pirfenidone in SSc-ILD. The known gastrointestinal, skin, and liver adverse events (AE) of pirfenidone are of importance given the involvement of these organs in SSc. METHODS: All patients received pirfenidone and were randomized 1:1 to either a 2- or 4-week titration starting at 801 mg/day and finishing at a maintenance dose of 2403 mg/day...
September 2016: Journal of Rheumatology
Padmanabha D Shenoy, Manish Bavaliya, Sujith Sashidharan, Kaveri Nalianda, Sreelakshmi Sreenath
BACKGROUND: Scleroderma is a systemic autoimmune disease characterized mainly by skin manifestations and involvement of various visceral organs, especially the lungs. Lung involvement is the leading cause of mortality in patients with scleroderma. There are data to suggest that cyclophosphamide (CYC) and mycophenolate mofetil (MMF) are effective in the management of scleroderma interstitial lung disease (SSc-ILD) but no head to head comparative data are available to date. METHODS: For the last 3 years, patients with SSc-ILD have been treated at our centre by protocol-based administration of intravenous CYC and MMF...
June 2, 2016: Arthritis Research & Therapy
Shinsuke Yasuda, Michihito Kono, Sanae Shimamura, Takashi Kurita, Toshio Odani, Tatsuya Atsumi
  Treatment of organ involvements accompanied by systemic autoimmune diseases is still challenging for clinicians, reminding the existence of unmet needs. Among them, lupus nephritis (LN), neuropsychiatric lupus, interstitial lung diseases (ILD) complicated with polymyositis/dermatomyositis (PM/DM) or systemic sclerosis (SSc) are the most severe conditions with poor prognosis. Because of the rarity and severity of the disease status, and of variety in evaluation methods, randomized clinical trials tend to be difficult in recruiting patients, in designing protocols, and in meeting primary endpoints...
2016: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
Claire Owen, Gene-Siew Ngian, Kathleen Elford, Owen Moore, Wendy Stevens, Mandana Nikpour, Candice Rabusa, Susanna Proudman, Janet Roddy, Jane Zochling, Catherine Hill, Allan Sturgess, Kathleen Tymms, Peter Youssef, Joanne Sahhar
OBJECTIVES: To report the efficacy and tolerability of mycophenolate mofetil (MMF) and azathioprine (AZA) in the management of systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: Patients in the Australian Scleroderma Cohort Study treated with at least 3 months of MMF or AZA for SSc-ILD confirmed on high resolution computed tomography (HRCT) chest were identified and their pulmonary function tests (PFTs) retrieved. Individuals with available results for T-1 (12 months prior to treatment commencement), T0 (date of treatment commencement) and at least one subsequent time point were included in the drug efficacy analysis...
September 2016: Clinical and Experimental Rheumatology
Guangfeng Zhang, Ting Xu, Hongwei Zhang, Shanhui Ye, Qingwen Wang, Lijun Zhang, Yunxia Lei, Riqiang Luo, Xiao Zhang
OBJECTIVE: To investigate the efficacy and safety of mycophenolate mofetil (MMF) in the treatment of connective tissue disease-related interstitial lung disease (CTD-ILD). METHODS: A total of 60 patients with CTD-ILD, confirmed by high resolution computer tomography (HRCT), were enrolled from five clinical centers from July 2010 to July 2014. In addition to the basic glucocorticoid treatment, patients received intravenous cyclophosphamide (Group A) or oral MMF (Group B) for one year...
December 1, 2015: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Susanna Cappelli, Silvia Bellando Randone, Gianna Camiciottoli, Amato De Paulis, Serena Guiducci, Marco Matucci-Cerinic
Interstitial lung disease (ILD) is common in systemic sclerosis (SSc) patients and despite recent advances in the treatment is, at present, the major cause of death. Today, an early diagnosis of ILD is possible, and is mandatory to improve the prognosis of the disease. Pulmonary function tests and high-resolution computed tomography remain the mainstay for the diagnosis of SSc-ILD, but there is a growing interest in lung ultrasound. Recently, the correlation between severity of fibrosis and some peripheral blood biomarkers has been described...
September 2015: European Respiratory Review: An Official Journal of the European Respiratory Society
Katarzyna Walkiewicz-Pielaszek, Monika Swacha, Barbara Bułło-Piontecka, Bolesław Rutkowski, Marzena Olesiñska
Mycophenolate mofetil (MMF) has been used in rheumatology for over 20 years. When transformed to the active metabolite of mycophenolic acid, it is a potent, selective, reversible inhibitor of inosine monophosphate dehydrogenase, a key enzyme of de novo purine synthesis, exerting a cytostatic effect on T and B cells. It also induces apoptosis of antigen-activated T cell clones, reduces the production of antibodies to inhibit the expression of adhesion molecules, reducing the influx of leukocytes and monocytes to inflammatory sites, and has anti-fibrotic properties...
February 6, 2015: Postȩpy Higieny i Medycyny Doświadczalnej
Michele Iudici, Giovanna Cuomo, Serena Vettori, Marialuisa Bocchino, Alessandro Sanduzzi Zamparelli, Salvatore Cappabianca, Gabriele Valentini
OBJECTIVE: To investigate the long-term disease course of patients with recently deteriorated systemic sclerosis (SSC)-interstitial lung disease (ILD) undergoing continuous immunosuppressive treatment with cyclophosphamide (CYC) as induction therapy. METHODS: A total of 45 consecutive SSc patients were treated with weekly pulses of 500mg of CYC up to 10-g cumulative dose followed by azathioprine (AZA) in those experiencing improvement (>10% increase) or stabilization of both forced vital capacity and diffusion lung capacity for carbon dioxide and by micophenolic acid (MMF) in those experiencing deterioration (>10% decrease of either parameter)...
February 2015: Seminars in Arthritis and Rheumatism
Spyros A Papiris, Konstantinos Kagouridis, Georgia Papadaki, Likurgos Kolilekas, Effrosyni D Manali
Fibrotic interstitial lung diseases (ILDs) are commonly encountered in scleroderma where they significantly influence prognosis. The mainstay of treatment in idiopathic fibrotic ILDs for the past 30 years was based on the combined administration of prednisone and cyclophosphamide (CYC) or prednisone, azathioprine plus N-acetyl cysteine, recently proved ineffective and harmful. Rheumatologists also despite "facts" showing that CYC treatment has no beneficial impact on fibrotic ILDs in scleroderma continue to commit the same, in a manner of speaking, "faults" by "treating their fibrotic ILDs by immunosuppressants...
April 2014: Lung
Susanna Cappelli, Silvia Bellando-Randone, Serena Guiducci, Marco Matucci-Cerinic
Since activation of the immune system and a perivascular infiltrate of inflammatory cells are key features of SSc, immunosuppression has long been considered to be an anchor treatment. Non-selective immunosuppression remains central to the treatment of interstitial lung disease (ILD) and skin involvement, with CYC most widely used to obtain remission. The use of MTX as a first-line agent may be considered in the presence of skin involvement without ILD. More recently, MMF has shown encouraging results in observational studies, but still needs more formal evaluation to verify if it can be considered an alternative drug to CYC or a maintenance agent such as AZA...
June 2014: Rheumatology
Isabel C Mira-Avendano, Joseph G Parambil, Ruchi Yadav, Valeria Arrossi, Meng Xu, Jeffrey T Chapman, Daniel A Culver
INTRODUCTION: We reviewed our experience with immunosuppressive agents in patients with steroid-resistant Interstitial Lung Disease in the setting of Polymyositis/Dermatomyositis (PM/DM-ILD) to determine whether there were major differences in outcomes. METHODS: We identified all patients treated for PM/DM-ILD and assessed cyclophosphamide (CYC), azathioprine (AZA) and mycophenolate (MMF) when used as first-line steroid sparing therapy for effects on pulmonary function variables, dyspnea and tolerance at six and twelve months...
June 2013: Respiratory Medicine
Aryeh Fischer, Kevin K Brown, Roland M Du Bois, Stephen K Frankel, Gregory P Cosgrove, Evans R Fernandez-Perez, Tristan J Huie, Mahalakshmi Krishnamoorthy, Richard T Meehan, Amy L Olson, Joshua J Solomon, Jeffrey J Swigris
OBJECTIVE: Small series suggest mycophenolate mofetil (MMF) is well tolerated and may be an effective therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). We examined the tolerability and longitudinal changes in pulmonary physiology in a large and diverse cohort of patients with CTD-ILD treated with MMF. METHODS: We identified consecutive patients evaluated at our center between January 2008 and January 2011 and prescribed MMF for CTD-ILD...
May 2013: Journal of Rheumatology
Argyris Tzouvelekis, Nikolaos Galanopoulos, Evangelos Bouros, George Kolios, George Zacharis, Paschalis Ntolios, Andreas Koulelidis, Anastasia Oikonomou, Demosthenes Bouros
UNLABELLED: Background. Interstitial lung disease (ILD) is the most common complication of systemic sclerosis (SSc) with treatment ineffective. OBJECTIVE: The aim of this meta-analysis was to provide an estimate of the safety and efficacy profile of Mycophenolate Mofetil (MMF) or sodium (MMS) in SSc-ILD patients. Materials and Methods. All studies were reviewed systematically. The main end-points were safety and efficacy profile as estimated by forced vital capacity (FVC)% and diffusion capacity of the lung for carbon monoxide (DL(CO))% of the predicted normal value (%pred...
2012: Pulmonary Medicine
Kyle M Walker, Janet Pope
OBJECTIVES: There is a need for standardization in systemic sclerosis (SSc) management. METHODS: SSc experts (n = 117) were sent 3 surveys to gain consensus for SSc management. RESULTS: First-line therapy for scleroderma renal crisis (SRC) was an angiotensin-converting enzyme inhibitor (ACEi). For SRC there were not many differences between treating mild or severe SRC. In general, Second-line was to add either a calcium channel blocker (CCB) or angiotensin receptor blocker (ARB) and then an alpha-blocker (66% agreed)...
August 2012: Seminars in Arthritis and Rheumatism
Argyris Tzouvelekis, Evangelos Bouros, Anastasia Oikonomou, Paschalis Ntolios, George Zacharis, George Kolios, Demosthenes Bouros
Background. Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease with ineffective treatment. Mycophenolate mofetil (MMF) is an immunomodulatory agent which inhibits lymphocyte proliferation. Objective. We sought to determine the safety and efficacy profile of MMF in IPF patients. Methods. We retrospectively identified ten patients, who met the ATS/ERS 2000 criteria for IPF and received MMF 2 gr/day for 12 months. All of them had routine laboratory, pulmonary function and radiological (high resolution computed tomography-HRCT) data available and were enrolled in the study...
2011: Pulmonary Medicine
Chikara Ogimi, Nazuna Honma, Risa Tanaka, Tsutomu Oh-ishi
A 6-year-old girl, who had received corticosteroid and cyclosporine on the diagnosis of interstitial pneumonitis related to juvenile dermatomyositis, developed severe thrombocytopenia. Her thrombocytopenia was resistant to repeated intravenous immunoglobulin administration and methylprednisolone pulse therapy. After additional treatment with mycophenolate mofetil (MMF), instead of cyclosporine, the thrombocytopenia improved, facilitating a reduction in the dose of corticosteroid without exacerbation of the interstitial pneumonitis...
April 2012: Modern Rheumatology
K Sampathkumar, M Ramakrishnan, A K Sah, S Gowtham, R N Ajeshkumar
Systemic vasculitides (SV) are a group of diseases with multi system involvement and varied clinical presentation. Anti-neutrophil cytoplasmic antibody (ANCA) testing has high sensitivity and specificity for SV. We describe the clinical course of four patients who had pauci-immune glomerulonephritis with systemic involvement without serological ANCA positivity; they were followed up for a cumulative 55 patient months. The mean Birmingham vasculitis score score was 23. All four had systemic symptoms with arthralgias and fever (100%)...
January 2010: Indian Journal of Nephrology
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