title: Sjögren Syndrome: Why Do Clinical Trials Fail?
abstract: Sjögren syndrome (SS) comprises glandular and extraglandular manifestations. Double-blind prospective trials of traditional disease-modifying antirheumatic 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.
authors.affiliation: Rheumatology Clinic, Scripps Memorial Hospital, XiMED Medical Group, 9850 Genesee Avenue, Suite 910, La Jolla, CA 92037, USA. Electronic address: robertfoxmd@mac.com.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Fox
authors.affiliation: Rheumatology Clinic, Scripps Memorial Hospital, XiMED Medical Group, 9850 Genesee Avenue, Suite 910, La Jolla, CA 92037, USA.
authors.forename: Carla M
authors.initials: CM
authors.lastname: Fox
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis; D001688:Biological Products / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003951:Diagnostic Errors; D017277:Drug Approval; D005060:Europe; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis; D000069283:Rituximab / Q000627:therapeutic use; D012595:Scleroderma, Systemic / Q000175:diagnosis; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D017211:Treatment Failure; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D000069283:Rituximab
keywords: Benign glandular manifestations; Danger hypothesis; Danger-associated molecular patterns; Extraglandular manifestations; Functional circuit; Keratoconjunctivitis sicca; Neurohypothalamic-immune axis; Sjögren syndrome