Subcutaneous Interferon ß-1a Administration by Electronic Auto-injector is Associated with High Adherence in Patients with Relapsing Remitting Multiple Sclerosis in a Real-life Study.

The objective was to investigate adherence measured by an electronic auto-injector device, and self-reported adherence and treatment convenience in subjects with relapsing remitting multiple sclerosis (RRMS), using an electronic auto-injector Rebismart® to self-inject interferon ß-1a. Thirty one patients with RRMS using the electronic auto-injector Rebismart® for self-injecting interferon ß-1a subcutaneously three times weekly were included in a real-life clinical multicenter study for 24 weeks in Finland. Mean adherence reported by the device and mean self-assessment of adherence were studied. Reasons for missing injections and treatment convenience were assessed. Association between adherence and gender and age were studied. The mean adherence calculated from the device data was 93.5%. The mean self-assessment of adherence was 96.6%. The most common reason for missing an injection was forget-fulness. Adherence (measured by the device) was not changed over time. In the high adherence group there were more females and young patients (<30 years of age). The auto-injector was found to substantially ease the treatment by 90% of the patients. The electronic auto-injector was associated with high adherence to treatment. The device was found to ease the patient's treatment and it was perceived as easy to use. It is a convenient tool to assess patient's adherence to treatment.

Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15.

AIM: An exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) ß-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing-remitting multiple sclerosis (RRMS). METHODS: Patients in the original PRISMS study were invited to a single follow-up visit 15 years after initial randomisation (PRISMS-15). Outcomes over 15 years were compared in the lowest and highest quartile of the cumulative sc IFN ß-1a dose groups, and according to total time receiving sc IFN ß-1a as a continuous variable per 5 years of treatment. Potential prognostic factors for outcomes were analysed. RESULTS: Of 560 patients randomised in PRISMS, 291 returned for PRISMS-15 and 290 (51.8%) were analysed. Higher cumulative dose exposure and longer treatment time appeared to be associated with better outcomes on: annualised relapse rate, number of relapses, time to Expanded Disability Status Scale (EDSS) progression, change in EDSS, proportions of patients with EDSS ≥ 4 or ≥ 6, ≤ 5 relapses and EDSS <4 or <6, and time to conversion to secondary-progressive MS (SPMS). Higher dose exposure was associated with lower proportions of patients with EDSS progression and conversion to SPMS, and longer time on treatment with lower risk of first relapse. Change in EDSS from baseline to 24 months was a strong predictor of evaluated clinical outcomes over 15 years. CONCLUSIONS: These findings suggest that higher cumulative exposure to sc IFN ß-1a may be associated with better clinical outcomes, and early change in EDSS score may have prognostic value, over many years, in RRMS.

Plasminogen activators and their inhibitors in human saliva and salivary gland tissue.

The purpose of this study was to identify plasminogen activators (PA) and their specific inhibitors in human cell-free saliva and to investigate their expression in salivary gland tissue. Saliva samples were obtained from 34 patients visiting a neurological out-patient department. The activities of tissue and urokinase plasminogen activators (tPA and uPA, respectively), the relative inhibition of tPA, and the amounts of plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2, respectively) in cell-free saliva were studied. The activities of tPA and uPA, and tPA inhibition, were measured using in-house microtiter plate assays, and PAI-1 and PAI-2 levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Immunohistochemistry was used to evaluate the expression of PAs and PAIs in the salivary gland. Tissue plasminogen activator activity was found in most samples, with a mean activity of 0.63 IU ml(-1). uPA was observed in only a few samples. PAI-1 was not detected, but PAI-2 was present in all samples (with a mean value of 11.1 ng ml(-1)). The mean PAI-2 level in women was 12.4 and in men was 7.6 ng ml(-1). The activity of tPA and the relative inhibition of tPA seemed to be inversely associated. Tissue plasminogen activator, PAI-1, and PAI-2 were evident in salivary gland tissue, whereas the expression of uPA was low. The tPA activity in saliva suggests an active proteolysis. Plasminogen activator inhibitor 2 was found to be the main inhibitor of PAs in saliva.