Improvement in relapse recovery with peginterferon beta-1a in patients with multiple sclerosis

Scott, Thomas F.; Kieseier, Bernd C.; Newsome, Scott D.; Arnold, Douglas L.; You, Xiaojun; Hung, Serena; Sperling, Bjoern

doi:10.1177/2055217316676644

Cited by 8 publications

(10 citation statements)

References 20 publications

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“…In ADVANCE, disability worsening was associated with worse scores on several HRQoL instruments (Newsome et al, 2015). The impact of disability worsening was attenuated by treatment with peginterferon beta-1a, potentially through a combination of reduction of relapse risk and improvement of relapse recovery (Newsome et al, 2017;Scott et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Matching-adjusted comparisons demonstrate better clinical outcomes in patients with relapsing multiple sclerosis treated with peginterferon beta-1a than with teriflunomide

Newsome

Mokliatchouk

Castrillo‐Viguera

et al. 2020

Multiple Sclerosis and Related Disorders

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Background: Peginterferon beta-1a and teriflunomide are both first-line disease-modifying therapies (DMTs) approved for the treatment of relapsing multiple sclerosis (RMS); however, no head-to-head trials have directly compared their clinical efficacy. We performed a matching-adjusted comparison of individual patient data from the peginterferon beta-1a pivotal phase 3 study, ADVANCE, and its extension study, ATTAIN, with pooled aggregated data from the teriflunomide pivotal phase 3 studies, TEMSO and TOWER. Methods: A total of 512 patients randomized to subcutaneous (SC) peginterferon beta-1a 125 mcg every 2 weeks in ADVANCE and 731 patients randomized to teriflunomide 14 mg daily (359 from TEMSO and 372 from TOWER) were matched on key baseline characteristics. After matching, weighted annualized relapse rate (ARR) and 24-week confirmed disability worsening (CDW) were calculated and compared for peginterferon beta-1aand teriflunomide-treated patients. A subset analysis comparing weighted ARR in patients who were newly diagnosed with RMS (diagnosis ≤1 year before study enrollment and disease-modifying therapy naïve) was also performed. Results: After matching, the peginterferon beta-1a and teriflunomide treatment groups were identically matched across baseline characteristics. The proportion of patients in the overall study populations with 24-week CDW at 108 weeks was significantly lower in the peginterferon beta-1a group than the teriflunomide group both before matching (8.5% vs 12.6%; P = 0.0249) and after matching (8.4% vs 12.6%; P = 0.0323). ARR at 108 weeks was numerically lower with peginterferon beta-1a than with teriflunomide both before matching (0.278 vs 0.354; P = 0.1326) and after matching (0.257 vs 0.354; P = 0.0510). Newly diagnosed patients treated with peginterferon beta-1a had numerically lower ARR than patients treated with teriflunomide both at 108 weeks (before matching: 0.225 vs 0.270; P = 0.587; after matching: 0.201 vs 0.270; P = 0.384) and at 5 years (before matching: 0.150 vs 0.196; after matching: 0.142 vs 0.196). Conclusions: In this matching-adjusted comparison of patients with RMS from three phase 3 trials, a significantly lower proportion of patients treated with SC peginterferon beta-1a 125 mcg every 2 weeks than with oral teriflunomide 14 mg once daily had 24-week CDW at 108 weeks. In addition, in both the overall population and newly diagnosed patient subgroups, ARR at 108 weeks was numerically lower with peginterferon beta-1a than with teriflunomide. The numerically lower ARR in newly diagnosed patients treated with peginterferon beta-1a compared with those treated with teriflunomide was sustained through up to 5 years of treatment.

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Section: Discussionmentioning

confidence: 99%

Matching-adjusted comparisons demonstrate better clinical outcomes in patients with relapsing multiple sclerosis treated with peginterferon beta-1a than with teriflunomide

Newsome

Mokliatchouk

Castrillo‐Viguera

et al. 2020

Multiple Sclerosis and Related Disorders

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“…3,4 Despite this critical role of relapse recovery in longterm prognosis in MS, relapse recovery has not been sufficiently modeled into clinical trials in early MS. Few studies have used relapse recovery as an outcome measure hypothesizing that disease-modifying treatments (DMTs) will help recovery from ensuing relapses after treatment initiation. 5,6 A common real-world practice in deciding immediate vs delayed DMT initiation in early MS often involves the extent and rapidity of a patient's recovery from early relapses, a decision for which there is no evidence from a clinical trial setting.…”

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confidence: 99%

Relapse recovery

Kantarci

Zeydan

Atkinson

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo determine whether basing the decision to initiate immediate vs delayed disease-modifying therapy (DMT) on extent of recovery after initial relapse affects long-term disability accumulation in a multiple sclerosis (MS) evidence-based setting.MethodsWe analyzed the double-blind, placebo-controlled interferon beta-1a 30 mc once a week in clinically isolated syndrome and 10-year-follow-up extension trial. Good recovery after presenting relapse was defined as (1) full early recovery within 28 days of symptom onset (Expanded Disability Status Scale [EDSS] score of 0 at enrollment maintained ≥6 months) and (2) delayed good recovery (EDSS score > 0 at enrollment and improvement from peak deficit to 6th-month or 1-year visit ≥ median). Time from recovery assignment to future disability (EDSS score ≥ 2.5 or ≥4.0) was studied on a relapse-recovery-stratified age axis and immediate vs 3-year delayed treatment initiation with Kaplan-Meier statistics and hazard ratios (HRs).ResultsOne hundred seventy-five/328 patients had good recovery (94 immediate and 81 delayed treatment); 153 did not have good recovery (77 immediate and 76 delayed treatment). HRs for EDSS score ≥2.5 outcome were: delayed treatment without good recovery as reference (HR = 1.0), delayed treatment with good recovery (HR6th-month: 0.67, p = 0.207; HR1st-year: 0.40, p = 0.027), immediate treatment without good recovery (HR6th-month: 0.56, p = 0.061; HR1st-year: 0.40, p = 0.011), and immediate treatment with good recovery (HR6th-month: 0.43, p = 0.014; HR1st-year: 0.48, p = 0.034). Placebo patients were switched to long-term treatment after 3 years, and insufficient EDSS score ≥4.0 outcome events were available to study.ConclusionsIn patients with MS presenting without good recovery after the initial relapse, immediate DMT initiation favorably influences the likelihood of more ambulatory-benign disease akin to patients with good recovery after the initial relapse.Classification of evidenceThis study provides Class III evidence that for patients with MS without good recovery after the initial relapse, immediate DMT initiation increases the likelihood of a benign disease course.

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“…Relapse recovery data are rarely reported in controlled treatment trails (and only as post‐hoc analyzes). Our study design mirrors a few prior efforts to estimate the short‐term impact of relapses on MS worsening in patients treated with DMTs . Prior studies also detailed changes in functional systems scores during relapses, showing strong agreement between 6 and 12 month confirmed changes, across multiple domains of the disability examinations (usually pyramidal system) …”

Section: Discussionmentioning

confidence: 57%

“…Prior studies have calculated relapse sequelae during short epochs, usually 1‐2 years, such as seen in medication trials . Ours is the first long‐term study examining the impact of recovery from each relapse in a large group of longitudinally followed RMS patients, seen from the time of diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…Clarification of this issue may determine the extent to which elimination of relapses through immunotherapy can result in long‐term benefits. Incomplete recovery from relapses implies a contribution of these circumscribed events to the irreversible process of tissue destruction . Better understanding of the impact of relapses vs slow progression may also help us understand the complex relationship between inflammation vs degeneration, which evolves over a lifetime of RMS.…”

Section: Introductionmentioning

confidence: 99%

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Multiple sclerosis relapses contribute to long‐term disability

et al. 2019

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The degree to which relapses with incomplete recovery (RW) contribute to the overall picture of worsening disability in relapse-onset multiple sclerosis (RMS) remains unclear. 1,2 Clarification of this issue may determine the extent to which elimination of relapses through immunotherapy can result in long-term benefits. Incomplete recovery from relapses implies a contribution of these circumscribed events to the irreversible process of tissue destruction. 3,4 Better understanding of the impact of relapses vs slow progression may also help us understand the complex relationship between inflammation vs degeneration, which evolves over a lifetime of RMS. Some epidemiologists opine that the majority of disability accumulated in MS over time results from a more or less degenerative process involving slow progression, whereas relapses contribute little to the long-term picture. 5 This view is challenged in more recent studies. 6,7 We sought to calculate the frequency of RW in the first 15 years of longitudinally followed RMS patients, using a clinical definition of incomplete recovery from relapse, and to compare the frequency of year-to-year slow progressive worsening (PW). Furthermore, we Background: Treatments affect both relapse-related disability and short-term disability change, but measurements of their impact on long-term outcomes remain a challenge.Objective: To ascertain the contribution of relapse-associated disability to overall disability in relapse-onset multiple sclerosis (RMS) using long-term data collected in our clinic. Materials and Methods: Retrospective study of a cohort of newly diagnosed patients with RMS, (n = 176) was undertaken, measuring all confirmed changes in disability up to 15 years after onset. Worsening was assessed yearly and in 5-year epochs and was attributed to either relapse (RW) or slow progression (PW). Results: At data lock, 139/176 (81%) of patients were still actively followed, with Expanded Disability Status Scale (EDSS) available for 10 years post-onset in 145/176 (82%) patients and 15 years post-onset EDSS in 83 patients (mean follow-up entire group 12.7 years post-onset). RW accounted for a large amount of worsening seen in the first 15 years of RMS. RW was less frequent over time, but accounted for most EDSS changes in the first decade of MS (167/267, 63% of EDSS changes), and remained important even in years 11-15 (17/50, 34% of EDSS changes). Median change in disability due to RW vs PW was similar over the entire 15 years.Conclusions: Worsening of treated MS was associated with relapses in many RMS patients throughout the first 15 years after onset, suggesting an opportunity for long-term benefit through relapse reduction. K E Y W O R D S expanded disability status scale, MS, progression, relapse | 337 SCOTT eT al.

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Improvement in relapse recovery with peginterferon beta-1a in patients with multiple sclerosis

Cited by 8 publications

References 20 publications

Matching-adjusted comparisons demonstrate better clinical outcomes in patients with relapsing multiple sclerosis treated with peginterferon beta-1a than with teriflunomide

Matching-adjusted comparisons demonstrate better clinical outcomes in patients with relapsing multiple sclerosis treated with peginterferon beta-1a than with teriflunomide

Relapse recovery

Multiple sclerosis relapses contribute to long‐term disability

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