Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2022 Jul 29;17(1):300.
doi: 10.1186/s13023-022-02455-x.

Natural history of Type 1 spinal muscular atrophy: a retrospective, global, multicenter study

Claude Cances  1   2 , Dmitry Vlodavets  3 , Giacomo Pietro Comi  4   5 , Riccardo Masson  6 , Maria Mazurkiewicz-Bełdzińska  7 , Kayoko Saito  8 , Edmar Zanoteli  9 , Angela Dodman  10 , Muna El-Khairi  11 , Ksenija Gorni  12 , Isaac Gravestock  13 , Janine Hoffart  12 , Renata S Scalco  10 , Basil T Darras  14 ; ANCHOVY Working Group
Collaborators, Affiliations
Multicenter Study

Natural history of Type 1 spinal muscular atrophy: a retrospective, global, multicenter study

Claude Cances et al. Orphanet J Rare Dis. .

Abstract

Background: ANCHOVY was a global, multicenter, chart-review study that aimed to describe the natural history of Type 1 spinal muscular atrophy (SMA) from a broad geographical area and provide further contextualization of results from the FIREFISH (NCT02913482) interventional study of risdiplam treatment in Type 1 SMA.

Methods: Data were extracted from medical records of patients with first symptoms attributable to Type 1 SMA between 28 days and 3 months of age, genetic confirmation of SMA, and confirmed survival of motor neuron 2 copy number of two or unknown. The study period started on 1 January 2008 for all sites; study end dates were site-specific due to local treatment availabilities. Primary endpoints were time to death and/or permanent ventilation and proportion of patients achieving motor milestones. Secondary endpoints included time to initiation of respiratory and feeding support.

Results: Data for 60 patients from nine countries across Asia, Europe and North and South America were analyzed. The median age (interquartile range [IQR]) for reaching death or permanent ventilation was ~ 7.3 (5.9-10.5) months. The median age (IQR) at permanent ventilation was ~ 12.7 (6.9-16.4) months and at death was ~ 41.2 (7.3-not applicable) months. No patients were able to sit without support or achieved any level of crawling, standing or walking.

Interpretation: Findings from ANCHOVY were consistent with published natural history data on Type 1 SMA demonstrating the disease's devastating course, which markedly differed from risdiplam-treated infants (FIREFISH Part 2). The results provide meaningful additions to the literature, including a broader geographical representation.

Keywords: ANCHOVY; FIREFISH; SMA natural history; Spinal muscular atrophy; Type 1 SMA.

PubMed Disclaimer

Conflict of interest statement

CC is a site principal investigator for Biogen and F. Hoffmann-La Roche Ltd clinical trials, and has received advisory fees from Novartis TG. VD and GPC have no conflicts of interest. RM has received fees from Biogen, F. Hoffmann-La Roche Ltd and Novartis Gene Therapies. MMB is a site principal investigator for Biogen and F. Hoffmann-La Roche Ltd clinical trials, and has received honoraria for advisory boards and speaker's fees from Biogen, F. Hoffmann-La Roche Ltd, and Novartis. KS is a site principal investigator for Biogen and Novartis Gene Therapies clinical trials, has received honoraria for advisory boards from Biogen, Novartis, and Roche/Chugai and speaker’s fees from Biogen and Novartis. IG and JH are employees of F. Hoffmann-La Roche Ltd. AD, MEK, KG and RSS are employees of, and hold shares in, F. Hoffmann-La Roche Ltd. BTD has received grants from Biogen, CureSMA, F. Hoffmann-La Roche Ltd, Fibrogen, Ionis Pharmaceuticals, U.S. National Institutes of Health/National Institute of Neurological Disorders and Stroke, PTC Therapeutics, Sarepta Pharmaceuticals, Slaney Family Fund for SMA, Spinal Muscular Atrophy Foundation, Summit and Working on Walking Fund; and is a board member for Amicus Inc., AveXis, Biogen, F. Hoffmann-La Roche Ltd grants, Genentech, Sarepta Pharmaceuticals and Vertex.

Figures

Fig. 1
Fig. 1
Time to death or permanent ventilation*: ANCHOVY. *Permanent ventilation was defined as ≥ 16 h of non-invasive ventilation per day for > 21 consecutive days, intubation for > 21 consecutive days, or tracheostomy. 90% CIs are calculated with a complementary log–log transformation for the estimated survival function, with standard errors computed via Greenwood’s formula. Patients with no recorded event are censored at the last age they were known to be event free. Two additional patients died after 24 months of age. CI, confidence interval
Fig. 2
Fig. 2
Time to respiratory support including permanent ventilation*: ANCHOVY. *Time from birth to first occurrence of awake-assisted, night-time-assisted, or nap-time-assisted ventilation, airway clearance through cough assistance or permanent ventilation (defined as ≥ 16 h of non-invasive ventilation per day for > 21 consecutive days, intubation for > 21 consecutive days, or tracheostomy). 90% CIs are calculated with a complementary log–log transformation for the estimated survival function, with standard errors computed via Greenwood’s formula. Patients with no recorded events are censored at the last age they were known to be event free. One additional patient required respiratory support after 24 months of age. CI, confidence interval
Fig. 3
Fig. 3
Time to feeding support*: ANCHOVY. *Feeding support included placement of nasogastric or nasojejunal tube or gastrostomy. 90% CIs are calculated with a complementary log–log transformation for the estimated survival function, with standard errors computed via Greenwood’s formula. Patients with no recorded events are censored at the last age they were known to be event free. There were no additional events recorded after 24 months of age. CI, confidence interval
Fig. 4
Fig. 4
Landmark comparison of time to death or permanent ventilation: ANCHOVY and FIREFISH Part 2. Kaplan–Meier curves are shown for FIREFISH (n = 41; solid black) and ANCHOVY (n = 40; solid blue). To compensate for the differences in age at the start of the risk period in the FIREFISH Part 2 and ANCHOVY studies, the landmark (dotted red vertical line) was set at the youngest age that a patient had an event in the FIREFISH Part 2 study, which was at an age of 6.1 months (186 days). ANCHOVY patients who had events before this time point are excluded. CI, confidence interval
See this image and copyright information in PMC

References

    1. Darras B, Monani U, De Vivo D. Genetic disorders affecting the motor neuron: spinal muscular atrophy. In: Swaiman K, Ashwal S, Ferriero D, Schor N, Finkel R, Gropman A, editors. Swaiman’s pediatric neurology: principles and practice. 6. Elsevier; 2017. pp. 1057–1064.
    1. Farrar MA, Kiernan MC. The genetics of spinal muscular atrophy: progress and challenges. Neurotherapeutics. 2015;12(2):290–302. doi: 10.1007/s13311-014-0314-x. - DOI - PMC - PubMed
    1. Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80(1):155–165. doi: 10.1016/0092-8674(95)90460-3. - DOI - PubMed
    1. Singh RN, Howell MD, Ottesen EW, Singh NN. Diverse role of survival motor neuron protein. Biochim Biophys Acta Gene Regul Mech. 2017;1860(3):299–315. doi: 10.1016/j.bbagrm.2016.12.008. - DOI - PMC - PubMed
    1. Lorson CL, Hahnen E, Androphy EJ, Wirth B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci U S A. 1999;96(11):6307–6311. doi: 10.1073/pnas.96.11.6307. - DOI - PMC - PubMed

Publication types

Associated data