BACKGROUND:Oral cladribine is the first oral pulsed therapy licensed for relapsing multiple sclerosis (RMS). Three years after the introduction into the European market, we evaluated practical aspects in the use of cladribine tablets, incorporating the experience gained in routine clinical practice and real-world studies. METHODS:Based on a structured review process, a panel of nine neurologists experienced in MS therapy discussed salient statements regarding the use of cladribine tables. For each statement the level of evidence was determined according to the levels of evidence recommended by the Centre for Evidence-Based Medicine, Oxford. The strength of each expert statement was then evaluated by means of a linear scale from 1 (very strong rejection) to 9 (very strong approval). Votes were collected by a formalized blinded process. Consent was considered to be reached if at least 75% of the experts agreed on a particular statement (i.e. voted for 7-9 points on the linear scale). RESULTS:. Statements include efficacy in early RMS, risk of side effects and infections, vaccination, pregnancy, and monitoring requirements. CONCLUSION:The consented recommendations summarize the practical experience inthe use of cladribine tablets in a real-world setting. These may provide guidance for unanswered questions arising with the introduction of new treatments such as cladribine tablets.

BACKGROUND:As patients with multiple sclerosis (MS) require lifelong treatment, optimization of therapy with respect to efficacy and safety is needed to limit long-term disease progression. Patients with MS also need a range of health-related services. Satisfaction with these as well as treatment is clinically relevant because satisfied patients are more likely to adhere to therapy. The aim of this study was to determine the status of patient satisfaction and of healthcare services in 70 specialized MS centres in Germany.METHODS:In 2011, patients with MS responded to a questionnaire, which solicited clinical and demographic information, as well as patients' perceptions of their overall situation and their satisfaction with treatment.RESULTS:Of 2791 patients surveyed, 81.9% had relapsing-remitting MS with mild disability [mean (standard deviation) Expanded Disability Status Scale score: 2.6 (1.8)]. Disease activity data were collected from 2205 patients, of whom 57.6% had remained relapse-free during the preceding 12 months. However, 38.9% had experienced one or more relapses, most of whom (67.3%) while receiving immunomodulatory treatment. About one-third of the patients indicated that they were more dissatisfied with their overall situation compared with the time before diagnosis. However, many patients (58.3%) were satisfied with their existing medication. Overall, 72.8% of patients would prefer oral to injectable treatments, assuming there was no difference in their efficacy.CONCLUSIONS:A substantial proportion of patients experienced breakthrough disease on treatment and may potentially benefit from a change of therapy. Although largely satisfied with treatment, most patients with MS would choose oral over injectable treatments.

Progressive multifocal leukoencephalopathy (PML) is a serious complication of natalizumab treatment in patients with relapsing-remitting MS (RRMS)1 with 638 confirmed cases as of March 2016. Therapeutic re-establishment of cerebral immune surveillance in PML management is complicated by immune reconstitution inflammatory syndrome (IRIS), an exuberant inflammatory response that aggravates damage caused by John Cunningham virus (JCV) infection and ultimately leads to a combined PML/IRIS syndrome.2 Currently, plasma exchange (PLEX) for the elimination of natalizumab and reconstitution of immune surveillance is used as standard of care, although this might lead to rebound MS activity or enhanced IRIS. Here, we report 2 cases of patients with PML/IRIS who did not receive PLEX, but were instead treated with the CCR5 antagonist maraviroc that has been associated with an amelioration of IRIS.3

OBJECTIVE:To describe the results of the PERSIST study, which prospectively evaluated once-weekly use of the intramuscular interferon beta-1a (IM IFNβ-1a) autoinjector (AVONEX PEN®) over 12 months in multiple sclerosis (MS) patients in a real-world clinical setting. BACKGROUND:The autoinjector was approved for the treatment of MS in Europe in 2011 and in the US in 2012. DESIGN/METHODS:PERSIST was a global, prospective, observational, open-label 12-month phase 4 study of MS patients self-administering IM IFNβ-1a therapy by autoinjector. Outcomes evaluated included physician-reported persistence and patient-reported compliance, tolerability, ease of use, and satisfaction. Preliminary 12-month data are available. RESULTS:A total of 274 MS patients (mean age 43.0 years; 75.8% female) were enrolled, with 219 defined as intent-to-treat patients; 158 patients have completed the 12-month visit. Among completers, 92.4% (146/158) of patients persisted on the autoinjector through month 12. Reasons given for nonpersistence included adverse events, disease progression, and loss to follow-up. Overall compliance (not missing any injections based on all available data) was 75.4% (150/199); the proportion of patients missing <20% of injections was 97.0% (193/199) over 12 months. Among patients who completed their injection-related questionnaires, 75.4% (92/122) reported injection-site pain levels ≤2 (0=no pain; 10=extremely painful); 74.4% (93/125) reported no injection-site reactions at month 12. The proportion of patients requiring injection assistance from a caregiver decreased from 10.0% (22/219) at baseline to 5.2% (7/134) at month 12. Similarly, fear of injection was reduced from 17.5% (38/217) at baseline to 2.4% (3/126) at month 12. Final 12-month findings will be presented. CONCLUSIONS:In this study, conducted in a real-world clinical setting, patient reports indicated that the IM IFNβ-1a autoinjector was well tolerated, easy to use, and associated with high levels of compliance and satisfaction; physician-reported persistence was also high. The self-reporting of several assessments was, it should be noted, a potential study limitation, possibly resulting in recall bias, incomplete data, and/or under-/overestimation of outcomes. Study Supported by:Biogen Idec Inc.

Objectives: The 12-month observational PERSIST study (NCT01405872) evaluated adherence associated with the intramuscular IFNβ-1a (i.m. IFN-β-1a) autoinjector pen in multiple sclerosis (MS) patients. Methods: MS patients initiating i.m. IFN-β-1a autoinjector treatment were prospectively assessed for physician-reported persistence (percentage of patients remaining on therapy) and patient-reported outcomes, including adherence (percentage of unmissed injections), compliance (percentage of patients missing no injections), tolerability (injection-site reactions [ISRs] and pain) and satisfaction. Results: The intent-to-treat population included 232 patients; of the 188 physician-reported 12-month completers, 182 patients remained on treatment (96.8% persistence). Monthly compliance rates were 87.5 – 96.2%. Mean monthly pain scores were 1.5 – 1.8 (scale: 0 = ‘no pain’; 10 = ‘extremely painful’). At 12 months, 73.5% of respondents reported no ISRs, 94.9% were satisfied/very satisfied with the autoinjector and 88.2% found using the device easy/very easy. Injection fear, injection anxiety and need for injection assistance by caregivers decreased from the initial visit to 12 months. No new safety signals were observed. Conclusions: The autoinjector pen is associated with high levels of persistence, compliance, adherence, and satisfaction, little-to-no pain and low need for caregiver assistance. Although these data are limited by reliance on patient questionnaires and the absence of a direct comparator group, this treatment may reduce barriers to injection therapy, while supporting long-term MS management.

Objective: Patient care in Multiple Sclerosis (MS) is complex and time-consuming because the needs differ depending on the individual health status and the degree of disability. Background The BEFORE study was conducted to picture the current status of MS care in daily practice and to identify current issues with the goal to optimize the quality of life of patients with MS. Design/Methods: A survey of 2800 patients was conducted from March to May 2011 in 70 specialized MS practices and centers by a questionnaire especially developed for this study. Results: The majority of the participating patients suffered from relapsing remitting MS (85%), half of the patients had an expanded disability status score (EDSS) of 2.0 or lower. Mean time since diagnosis was 10.4 years. The interviewed MS patients were generally satisfied with the care given by treating physicians and the involved health service provider. With respect to their current treatment, only about 10% of patients reported not to be satisfied. 43% had previously abrogated or interrupted therapy. Reasons for that were side effects in 58% and injection-site problems in 39% cases. Of those patients who suffered from relapses during the previous 12 months, 67% reported to have received immunomodulating therapy. The last MRI showed 11.8 lesions on average. Nearly all patients rated better effectiveness to be most essential for new treatments in terms of reduction of disability progression and relapse rate. Providing equal efficacy, patients clearly prefer an oral therapy (75%), followed by subcutaneous (11%), intravenous (9%) and intramuscular injection (5%), respectively. Conclusions: Patients with MS were generally satisfied with their care and show long-term adherence, but still expect improvements for future MS therapy options. The Patients9 main choice would be an oral therapy with better effectiveness and tolerability. Disclosure: Dr. Becker has received personal compensation for activities with Novartis as member of a scientific advisory board. Dr. Becker has received research support from Novartis, Merck-Serono, Biogen Idec and Bayer Health care. Dr. Elias has received personal compensation for activities with Novartis, Pharma GmbH, Merck & Co., Biogen Idec as a member of a scientific advisory board. Dr. Elias has received research support from Novartis, Pharma GmbH, Merck & Co., Biogen Idec and Bayer Pharmeceuticals Corporation. Dr. Lueer has received personal compensation for activities with Merck Serono, Biogen Idec, Novartis Pharma GmbH, and Bayer Health Care.Dr. Lueer has received research support from Biogen Idec, Merck Serono, Bayer Health Care, and Novartis Pharma GmbH. Dr. Heeschen has received personal compensation for activities with Novartis as employee. Dr. Tracik has received personal compensation for activities with Novartis as an employee. Dr. Ortler has received personal compensation for activites with Novartis as an employee. Dr. Haas has received personal compensation for activities with Bayer Schering, Teva Aventis, Merck Serono, Biogen Idec, Allergan, and Octapharma.

The majority of patients with migraine headaches are treated in non-specialized institutions though data on treatment outcomes are largely derived from tertiary care centers. The current non-interventional study explores efficacy and tolerability outcomes of patients with episodic migraines receiving topiramate as preventive agent in a general practice setting. A total of 366 patients (87% female, mean age 41.8 ± 11.6 years) were eligible for migraine prevention and treated with flexible dose topiramate for 6 months (core phase), and optionally for a total of 12 months (follow-up phase). Overall, 261 patients (77.7% of safety analysis set, SAF) completed the core phase. Reasons for discontinuation included adverse events (2.1%), lost to follow-up (1.8%), other reasons (1.5%), and end of therapy (0.3%) though in the majority of patients who discontinued no reasons were listed. The median daily dose at endpoint was 50 mg/day (range, 25–187.5 mg/day). The median days with migraine headaches decreased from 6.0 to 1.2 days ( p < 0.001), median pain intensity score decreased from 17.0 to 3.2 points ( p < 0.001). In women with reported menstruation-associated migraine, the median number of migraine attacks decreased from 4.0 to 0.9 ( p < 0.001). Absenteeism as well as triptan use decreased significantly, and significant improvements in activities of daily living and quality of life were reported. The most frequently reported AEs were paraesthesia (4.2%) and nausea (3%). Results suggest that migraine prevention with topiramate in a general practice is generally well tolerated and associated with a significant improvement in migraine headaches and related functional impairment.