Sjogren Syndrome Why Do Clinical Trials Fail?

被引：17

作者：

Fox, Robert I. ^{[1
]}

Fox, Carla M. ^{[1
]}

机构：

[1] XiMED Med Grp, Scripps Mem Hosp, Rheumatol Clin, 9850 Genesee Ave,Suite 910, La Jolla, CA 92037 USA

来源：

RHEUMATIC DISEASE CLINICS OF NORTH AMERICA | 2016年 / 42卷 / 03期

关键词：

Sjogren syndrome; Benign glandular manifestations; Extraglandular manifestations; Keratoconjunctivitis sicca; Danger hypothesis; Danger-associated molecular patterns; Functional circuit; Neurohypothalamic-immune axis; INNATE IMMUNE RECOGNITION; DRY EYE; CHRONIC FATIGUE; OCULAR SURFACE; MULTIPLE-SCLEROSIS; RITUXIMAB; AUTOANTIBODIES; ANTINUCLEAR; MECHANISMS; AUTOIMMUNE;

D O I：

10.1016/j.rdc.2016.03.009

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Sjogren syndrome (SS) comprises glandular and extraglandular manifestations. Double-blind prospective trials of traditional disease-modifying anti rheumatic drugs and biologics have failed because they have not improved benign symptoms, the major cause of lowered quality of life. Rituximab has proven effective in SS patients with associated mixed cryoglobulinemia, parotid gland swelling, lymphocytic interstitial pneumonitis, thrombocytopenia, and other manifestations. There were few of these SS patients in the trials required for FDA approval. Most patients had benign symptoms and did not show benefit, leading to failure of the study. This article examines the reasons for these failures and proposes future directions.

引用

页码：519 / +

页数：13

共 54 条

[1] Evaluation of Histologic, Serologic, and Clinical Changes in Response to Abatacept Treatment of Primary Sjogren's Syndrome: A Pilot Study [J].

Adler, Sabine ;

Koerner, Meike ;

Foerger, Frauke ;

Huscher, Doerte ;

Caversaccio, Marco-Domenico ;

Villiger, Peter M. .

ARTHRITIS CARE & RESEARCH, 2013, 65 (11) :1862-1868

[2] Type I interferon is a therapeutic target for virus-induced lethal vascular damage [J].

Baccala, Roberto ;

Welch, Megan J. ;

Gonzalez-Quintial, Rosana ;

Walsh, Kevin B. ;

Teijaro, John R. ;

Nguyen, Anthony ;

Ng, Cherie T. ;

Sullivan, Brian M. ;

Zarpellon, Alessandro ;

Ruggeri, Zaverio M. ;

de la Torre, Juan Carlos ;

Theofilopoulos, Argyrios N. ;

Oldstone, Michael B. A. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (24) :8925-8930

[3] Heat shock proteins and chronic fatigue in primary Sjogren's syndrome [J].

Bardsen, Kjetil ;

Nilsen, Mari Maeland ;

Kvaloy, Jan Terje ;

Norheim, Katrine Braekke ;

Jonsson, Grete ;

Omdal, Roald .

INNATE IMMUNITY, 2016, 22 (03) :162-167

[4]

Bowman SJ, 2012, CURR PHARM BIOTECHNO, V13, P1997

[5] Estimating Indirect Costs in Primary Sjogren's Syndrome [J].

Bowman, Simon J. ;

Pierre, Yvan St. ;

Sutcliffe, Nurhan ;

Isenberg, David A. ;

Goldblatt, Fiona ;

Price, Elizabeth ;

Hamburger, John ;

Richards, Andrea ;

Rauz, Saaeha ;

Regan, Marian ;

Rigby, Shirley ;

Jones, Adrian ;

Mulherin, Diarmuid ;

Clarke, Ann E. .

JOURNAL OF RHEUMATOLOGY, 2010, 37 (05) :1010-1015

[6] Case 14-2011: A Woman with Asymmetric Sensory Loss and Paresthesias [J].

Chad, David A. ;

Stone, John H. ;

Gupta, Rajiv .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (19) :1856-1865

[7] Mechanism of Action of Oral Fingolimod (FTY720) in Multiple Sclerosis [J].

Chun, Jerold ;

Hartung, Hans-Peter .

CLINICAL NEUROPHARMACOLOGY, 2010, 33 (02) :91-101

[8] Associations Between Salivary Gland Histopathologic Diagnoses and Phenotypic Features of Sjogren's Syndrome Among 1,726 Registry Participants [J].

Daniels, Troy E. ;

Cox, Darren ;

Shiboski, Caroline H. ;

Schiodt, Morten ;

Wu, Ava ;

Lanfranchi, Hector ;

Umehara, Hisanori ;

Zhao, Yan ;

Challacombe, Stephen ;

Lam, Mi Y. ;

De Souza, Yvonne ;

Schiodt, Julie ;

Holm, Helena ;

Bisio, Patricia A. M. ;

Gandolfo, Mariana S. ;

Sawaki, Toshioki ;

Li, Mengtao ;

Zhang, Wen ;

Varghese-Jacob, Beni ;

Ibsen, Per ;

Keszler, Alicia ;

Kurose, Nozomu ;

Nojima, Takayuki ;

Odell, Edward ;

Criswell, Lindsey A. ;

Jordan, Richard ;

Greenspan, John S. .

ARTHRITIS AND RHEUMATISM, 2011, 63 (07) :2021-2030

[9] Neural regulation of lacrimal gland secretory processes: Relevance in dry eye diseases [J].

Dartt, Darlene A. .

PROGRESS IN RETINAL AND EYE RESEARCH, 2009, 28 (03) :155-177

[10] Reduction of fatigue in Sjogren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study [J].

Dass, S. ;

Bowman, S. J. ;

Vital, E. M. ;

Ikeda, K. ;

Pease, C. T. ;

Hamburger, J. ;

Richards, A. ;

Rauz, S. ;

Emery, P. .

ANNALS OF THE RHEUMATIC DISEASES, 2008, 67 (11) :1541-1544

← 1 2 3 4 5 6 →