Percent change from MOR-004 baseline in 6-min walk test (6MWT) distance at 2Â years in the MOR-005 Modified Per-Protocol (MPP) population (excluding patients who had orthopedic surgery during the extension study or missed âĽ20% of their scheduled elosulfase alfa infusions) and comparable, untreated patients from the MorCAP natural history study. (DOCX 12Â kb

Ian Noble (3950522)

Kathryn Evans (3464480)

Kaustuv Bhattacharya (3950516)

Roberto Giugliani (398540)

Rudolf Schrover (3950519)

Orphanet Journal of Rare Diseases

Morquio A syndrome is an ultra-rare, inherited lysosomal storage disorder associated with progressive, multisystemic clinical impairments, causing gradual loss of functional capacity and endurance, impaired quality of life, and early mortality. Studies in Morquio A patients have used the 6-min walk test (6MWT) to assess functionality and endurance and to evaluate disease progression or efficacy of treatment. The objective of the present study was to review minimal clinically important differences (MCIDs) for the 6MWT reported for disease states that widely use the 6MWT to evaluate clinical benefit and to discuss the results in view of the challenges in estimating MCID for ultra-rare diseases, using the case of elosulfase alfa in Morquio A patients. A systematic literature search was performed using Embase and Medline to identify studies specifically estimating the MCID using either anchor-based or distributionbased methods. A total of 19 publications on 17 studies were identified; none of these included patients with Morquio A syndrome or the wider disease category of lysosomal storage disorders. Therefore, the MCIDs determined by studies in patients with respiratory, cardiovascular, or musculoskeletal disease were compared to changes in the 6MWT seen in Morquio A patients in the pivotal phase 3 clinical trial of elosulfase alfa enzyme replacement therapy.  The literature review showed a mean MCID for the 6MWT of 7% change (range 3–15%) in studies using anchor-based methods and a 9% change (range 4–16%) using distribution-based methods. Results of the elosulfase alfa clinical trial and its extension showed a placebo-adjusted 14.9% improvement in the 6MWT from baseline at week 24, which was greater than the mean MCID based on the results of the systematic literature review. After 2 years, 6MWT distance increased by a mean of 20.7% from baseline in a modified per-protocol population, versus a reduction of 6.9% in comparable untreated patients from the MorCAP natural history study over the same period. Although further research is required to establish the MCID of the 6MWT in Morquio A patients, the presented data provide further evidence for the positive effect of elosulfase alfa in this patient population

Schrover, Rudolf

Evans, Kathryn

Giugliani, Roberto

Noble, Ian

Bhattacharya, Kaustuv

Universidade Federal do Rio Grande do Sul

Minimal clinically important difference for the 6-min walk test : literature review and application to Morquio A syndrome

Lume 5.8

English

Abstract Morquio A syndrome is an ultra-rare, inherited lysosomal storage disorder associated with progressive, multi-systemic clinical impairments, causing gradual loss of functional capacity and endurance, impaired quality of life, and early mortality. Studies in Morquio A patients have used the 6-min walk test (6MWT) to assess functionality and endurance and to evaluate disease progression or efficacy of treatment. The objective of the present study was to review minimal clinically important differences (MCIDs) for the 6MWT reported for disease states that widely use the 6MWT to evaluate clinical benefit and to discuss the results in view of the challenges in estimating MCID for ultra-rare diseases, using the case of elosulfase alfa in Morquio A patients. A systematic literature search was performed using Embase and Medline to identify studies specifically estimating the MCID using either anchor-based or distribution-based methods. A total of 19 publications on 17 studies were identified; none of these included patients with Morquio A syndrome or the wider disease category of lysosomal storage disorders. Therefore, the MCIDs determined by studies in patients with respiratory, cardiovascular, or musculoskeletal disease were compared to changes in the 6MWT seen in Morquio A patients in the pivotal phase 3 clinical trial of elosulfase alfa enzyme replacement therapy. The literature review showed a mean MCID for the 6MWT of 7% change (range 3–15%) in studies using anchor-based methods and a 9% change (range 4–16%) using distribution-based methods. Results of the elosulfase alfa clinical trial and its extension showed a placebo-adjusted 14.9% improvement in the 6MWT from baseline at week 24, which was greater than the mean MCID based on the results of the systematic literature review. After 2 years, 6MWT distance increased by a mean of 20.7% from baseline in a modified per-protocol population, versus a reduction of 6.9% in comparable untreated patients from the MorCAP natural history study over the same period. Although further research is required to establish the MCID of the 6MWT in Morquio A patients, the presented data provide further evidence for the positive effect of elosulfase alfa in this patient population

Rudolf Schrover

Kathryn Evans

Roberto Giugliani

Ian Noble

Kaustuv Bhattacharya

Directory of Open Access Journals

Minimal clinically important difference for the 6-min walk test: literature review and application to Morquio A syndrome

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