Emerging treatment for Sjögren's disease: a review of recent phase II and III trials.

INTRODUCTION: Sjögren's Disease, SjD, is a systemic autoimmune disorder characterized by reduced function of the salivary and lacrimal glands. Patients suffer from dryness, fatigue, and pain and may present with or without extra-glandular organ involvement. Symptoms limit SjD patients' quality of life and are the most difficult to improve with therapy. SjD patients are heterogeneous and clustering them into biologically similar subgroups might improve the efficacy of therapies. The need for therapies that address both the symptoms and extra glandular organ involvement of SjD presents an unmet opportunity that has recently attracted a growing interest in the pharmaceutical industry. AREAS COVERED: The goal of this report is to review recent phase II/III studies in SjD. To accomplish our goal, we performed a literature search for phase II/III studies and abstracts recently presented at conferences. EXPERT OPINION: This review allows updates the reader on the multitude of recent phase II/III clinical trials. We speculate on how subtypes of SjD will drive future therapeutic targeting and inform pathogenesis.

Treatment of Sjögren's syndrome: current therapy and future directions.

SS is usually described as having severe fatigue, dryness, diffuse pain, glandular swelling, and various extraglandular (systemic) manifestations. Clinical trials have generally failed because the vast majority of enrolled patients had no extraglandular manifestations at the time of enrolment but suffered from fatigue, dryness and pain that did not significantly respond to the study medication. A number of hypotheses on the pathogenesis of pSS have been put forward, including disturbances of innate and adaptive immunity as well as abnormalities of the interface between immune disorders and the neuro-endocrine system related to lacrimal and secretory gland dysfunction. Thus, future therapies must be designed for improvement of the symptoms of dry eyes and dry mouth, extraglandular disease, and fatigue and cognitive deficits. Given the inadequacies and limitations of current treatment options, we suggest that innovative directions involving interactions with neuroscientists and neuropsychiatrists together or combined with new immune targeting may be hold promise for better treating pSS.

Sjögren Syndrome: Why Do Clinical Trials Fail?

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.