Treatment of primary sjögren's syndrome with low‐dose human interferon alfa administered by the oromucosal route: Combined phase III results

Abstract

Objective. This study tested the safety and efficacy of human interferon (IFN) alfa for treatment of salivary hypofunction and dry mouth symptoms in primary Sjö gren's syndrome patients. Methods. Combined results are reported from 2 phase III clinical trials in which a total of 497 subjects with primary Sjö gren's syndrome received 150 international units of human IFN alfa or matching placebo 3 times per day for 24 weeks by the oromucosal route. Results. Subjects given IFN alfa had a significantly (P ‫؍‬ 0.01) greater mean increase in unstimulated whole saliva (UWS) flow, compared with subjects given placebo. In IFN alfa patients, increases in UWS correlated positively and significantly with improvements noted in 7 of 8 symptoms associated with oral and ocular dryness. The coprimary endpoints of stimulated whole saliva flow and oral dryness were not significantly improved in the IFN alfa group relative to placebo. No significant differences were found between the groups with respect to overall adverse event incidence or severity. Conclusion. IFN alfa given at low dosage by the oromucosal route can significantly increase UWS flow in patients with primary Sjö gren's syndrome, without causing significant adverse events.

Ability of Orally Administered IFN-.ALPHA.4 to Inhibit Naturally Occurring Gingival Inflammation in Dogs

“…Low dose administration of IFN- is defined as IFN- administration with the amount of 0.05-1000 IU/kg, compared to high dose administration of IFN-, which is one of the traditional treatments by intramuscular or subcutaneous injection applied to hepatitis C, uses several hundreds to ten million IU/kg [39]. Human IFN- (HuIFN-) has been given orally in low doses to treat or prevent a number of infectious and immune-based diseases in a variety of species [2,7,14,26]. Notably, the oral administration of natural HuIFN- has been shown to be therapeutic in respiratory tract infections in cattle [6,13].…”

“…Recently, it has been reported that low dose oral administration (LDOA) of type I IFN is effective against chronic diseases and infectious diseases [2,6,7,13,14]. The mechanism of systemic immune response regulation by LDOA of IFN- is suggested as humoral or cellmediated via mucosal epithelial cells [5,11,37,38,41].…”

Diagnosis and treatment of primary Sjogren’s syndrome: an update

“…In one large double-blinded, placebo-controlled randomized controlled trial, interferon alpha was given via oromucosal route. Unfortunately, the drug failed to show benefit in reducing oral dryness and stimulated salivary flow [29].…”

Primary Sjögren’s Syndrome: Current Pathophysiological, Diagnostic and Therapeutic Advances

“…Besides antiviral effects, IFN- has immunomodulating properties. Four pilot studies have shown beneficial effects of oromucosal IFN-, whereby salivary flow was increased and salivary gland histology after treatment demonstrated reduced lymphocytic infiltrâtes (Cummins et al, 2003;Tobon et al, 2010). A phase III trial performed later, showed an increase in unstimulated salivary flow but the main clinical endpoint, which was improvement of stimulated salivary flow, was not met.…”