Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as “lack of efficacy” (3.3% vs. 1.7%), “scheduled stop” (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from “real-world” database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry

BURDEN OF MULTIPLE SCLEROSIS IN GERMANY - A MATCHED COHORT STUDY USING A LARGE CLAIMS DATABASE

Koenig C, Altevers J, Maas C, et al. BURDEN OF MULTIPLE SCLEROSIS IN GERMANY - A MATCHED COHORT STUDY USING A LARGE CLAIMS DATABASE. In: VALUE IN HEALTH. Vol 22. New york: Elsevier Science Inc; 2019: S745

Evaluation of Study and Patient Characteristics of Clinical Studies in Primary Progressive Multiple Sclerosis: A Systematic Review

<div><p>Background</p><p>So far, clinical studies in primary progressive MS (PPMS) have failed to meet their primary efficacy endpoints. To some extent this might be attributable to the choice of assessments or to the selection of the study population.</p><p>Objective</p><p>The aim of this study was to identify outcome influencing factors by analyzing the design and methods of previous randomized studies in PPMS patients without restriction to intervention or comparator.</p><p>Methods</p><p>A systematic literature search was conducted in MEDLINE, EMBASE, BIOSIS and the COCHRANE Central Register of Controlled Trials (inception to February 2015). Keywords included PPMS, primary progressive multiple sclerosis and chronic progressive multiple sclerosis. Randomized, controlled trials of at least one year’s duration were selected if they included only patients with PPMS or if they reported sufficient PPMS subgroup data. No restrictions with respect to intervention or comparator were applied. Study quality was assessed by a biometrics expert. Relevant baseline characteristics and outcomes were extracted and compared.</p><p>Results</p><p>Of 52 PPMS studies identified, four were selected. Inclusion criteria were notably different among studies with respect to both the definition of PPMS and the requirements for the presence of disability progression at enrolment. Differences between the study populations included the baseline lesion load, pretreatment status and disease duration. The rate of disease progression may also be an important factor, as all but one of the studies included a large proportion of patients with a low progression rate. In addition, the endpoints specified could not detect progression adequately.</p><p>Conclusion</p><p>Optimal PPMS study methods involve appropriate patient selection, especially regarding the PPMS phenotype and progression rate. Functional composite endpoints might be more sensitive than single endpoints in capturing progression.</p></div

Median change from baseline in T25W in the OLYMPUS study (reported by Hawker et al. as z-score; the Z-score is calculated by subtracting the baseline mean from each individual test result and then dividing by the standard deviation of the baseline values to obtain a standardized score for each individual); * p<0.05 compared to placebo.

<p>Median change from baseline in T25W in the OLYMPUS study (reported by Hawker et al. as z-score; the Z-score is calculated by subtracting the baseline mean from each individual test result and then dividing by the standard deviation of the baseline values to obtain a standardized score for each individual); * p<0.05 compared to placebo.</p

MRI results.

<p>n/a: not available; ns: not significant.</p><p>MRI results.</p

Studies excluded from further evaluation.

<p>ASCT: autologous stem cell transplantation; IFN: Interferon; n/a: not available; SD = standard deviation; TLI: Total lymphoid irradiation; yrs: years.</p><p>^a: group size not specified</p><p>^b: single arm study</p><p>MS subtypes: CP = chronic progressive; P = primary progressive MS; iP = primary progressive MS with inflammatory activity; PR = progressive relapsing MS; R = relapsing remitting MS; S = secondary progressive MS; rfS = relapse-free secondary progressive MS; tMS = transitional MS;</p><p>Reasons for exclusion: A = insufficient PPMS subgroup data available; B = only Conference Abstract available, insufficient design information and group data for further evaluation; C = single-arm study; D = study duration < 1 year.</p><p>Studies excluded from further evaluation.</p

Results from the timed 10-meter walk in the study by Leary et al. (median time in seconds).

<p>Results from the timed 10-meter walk in the study by Leary et al. (median time in seconds).</p

Published results—Baseline characteristics.

<p>GA: Glatiramer acetate; IVIg: intravenous immunoglobulin; IFN: Interferon; n/a: not available; yrs: years</p><p>^a: the publication does not name, whether duration since diagnosis or since first symptom is reported. It is assumed, that the value refers to the duration since first symptom.</p><p>Published results—Baseline characteristics.</p