Treatment Satisfaction in 5q-spinal Muscular Atrophy Under Nusinersen Therapy

Overview

Journal Ther Adv Neurol Disord

Specialty Neurology

Date 2021 Mar 22

PMID 33747131

Citations 10

Authors

Alma Osmanovic

Gresa Ranxha

Mareike Kumpe

Claudia D Wurster

Benjamin Stolte

Isabell Cordts

Rene GuNTHER

Maren Freigang

Lars H Muschen

Camilla Binz

Andreas Hermann

Marcus Deschauer

Paul Lingor

Albert C Ludolph

Tim Hagenacker

Olivia Schreiber-Katz

Susanne Petri

Affiliations

Soon will be listed here.

Abstract

Background: Nusinersen was the first approved disease-modifying therapy for all 5q-spinal muscular atrophy (SMA) patients regardless of age or disease severity. Its efficacy in adults has recently been demonstrated in a large cohort by motor outcome measures, which were only partially suitable to detect changes in very mildly or severely affected patients. Patient-reported outcome measures (PROs) have been suggested as a valuable addition. Here, we aimed to assess treatment satisfaction and investigate whether it may be a useful PRO to monitor SMA patients.

Methods: We enrolled 91 mainly adult 5q-SMA patients treated with nusinersen in a national, multicenter, cross-sectional observational study. 21 patients underwent longitudinal follow up. Patients' satisfaction with treatment in four dimensions (global, effectiveness, convenience, side effects) was assessed by the Treatment Satisfaction Questionnaire for Medication German version 1.4 (TSQM-1.4) and related to clinical parameters, motor scores, and treatment duration.

Results: More than 90% of SMA patients were consistently satisfied over a median treatment duration of 10 months. Highest mean scores were observed in the dimensions 'side effects,' 'global satisfaction,' and 'effectiveness' (93.5 ± 14.8 73.1 ± 21.0 and 64.8 ± 20.6, respectively). Patients' satisfaction with the convenience of treatment was considerably lower (43.6 ± 20.2). Interestingly, satisfaction with the effectiveness was higher in ambulatory ( = 0.014) compared with non-ambulatory patients and directly correlated to motor outcome measures. Five non-ambulatory patients withdrew from therapy. All of them presented with a deterioration of motor outcome measures and reported dissatisfaction with treatment effectiveness and convenience.

Conclusion: Most patients were satisfied with nusinersen treatment effectiveness. Less severely affected patients indicated higher satisfaction. The TSQM-1.4 helped to identify therapy non-responders, who mainly addressed dissatisfaction with effectiveness and convenience. We suggest introducing the TSQM-1.4 as an additional PRO in SMA into clinical practice.

Citing Articles

Identification of the most relevant aspects of spinal muscular atrophy (SMA) with impact on the quality of life of SMA patients and their caregivers: the PROfuture project, a qualitative study.

de Lemus M, Cattinari M, Pascual S, Medina J, Garcia M, Magallon A J Patient Rep Outcomes. 2024; 8(1):78.

PMID: 39044101 PMC: 11266339. DOI: 10.1186/s41687-024-00758-0.

Risdiplam therapy in adults with 5q-SMA: observational study on motor function and treatment satisfaction.

Bjelica B, Wohnrade C, Cespedes I, Osmanovic A, Schreiber-Katz O, Petri S BMC Neurol. 2024; 24(1):67.

PMID: 38368338 PMC: 10873992. DOI: 10.1186/s12883-024-03562-x.

Consensus from the Brazilian Academy of Neurology for the diagnosis, genetic counseling, and use of disease-modifying therapies in 5q spinal muscular atrophy.

Zanoteli E, Araujo A, Becker M, Fortes C, Franca Jr M, Machado-Costa M Arq Neuropsiquiatr. 2024; 82(1):1-18.

PMID: 38316428 PMC: 10843933. DOI: 10.1055/s-0044-1779503.

Satisfaction with medication in older adult patients with chronic respiratory diseases: a multicenter cross-sectional observational study.

Wu J, Meng W, Zeng H, Ma Y, Chen Y Front Public Health. 2023; 11:1168249.

PMID: 37670823 PMC: 10476521. DOI: 10.3389/fpubh.2023.1168249.

Measuring Fatigue and Fatigability in Spinal Muscular Atrophy (SMA): Challenges and Opportunities.

Rodriguez-Torres R, Uher D, Gay E, Coratti G, Dunaway Young S, Rohwer A J Clin Med. 2023; 12(10).

PMID: 37240564 PMC: 10218827. DOI: 10.3390/jcm12103458.

References

Kaufmann P, McDermott M, Darras B, Finkel R, Sproule D, Kang P . Prospective cohort study of spinal muscular atrophy types 2 and 3. Neurology. 2012; 79(18):1889-97. PMC: 3525313. DOI: 10.1212/WNL.0b013e318271f7e4. View

Glanzman A, OHagen J, McDermott M, Martens W, Flickinger J, Riley S . Validation of the Expanded Hammersmith Functional Motor Scale in spinal muscular atrophy type II and III. J Child Neurol. 2011; 26(12):1499-507. DOI: 10.1177/0883073811420294. View

Cedarbaum J, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B . The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci. 1999; 169(1-2):13-21. DOI: 10.1016/s0022-510x(99)00210-5. View

Bortolani S, Stura G, Ventilii G, Vercelli L, Rolle E, Ricci F . Intrathecal administration of nusinersen in adult and adolescent patients with spinal muscular atrophy and scoliosis: Transforaminal versus conventional approach. Neuromuscul Disord. 2019; 29(10):742-746. DOI: 10.1016/j.nmd.2019.08.007. View

Finkel R, Mercuri E, Darras B, Connolly A, Kuntz N, Kirschner J . Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017; 377(18):1723-1732. DOI: 10.1056/NEJMoa1702752. View

Osmanovic A, Ranxha G, Kumpe M, Muschen L, Binz C, Wiehler F . Treatment expectations and patient-reported outcomes of nusinersen therapy in adult spinal muscular atrophy. J Neurol. 2020; 267(8):2398-2407. PMC: 7359174. DOI: 10.1007/s00415-020-09847-8. View

Darras B, Chiriboga C, Iannaccone S, Swoboda K, Montes J, Mignon L . Nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1/2 studies. Neurology. 2019; 92(21):e2492-e2506. PMC: 6541434. DOI: 10.1212/WNL.0000000000007527. View

Ratni H, Ebeling M, Baird J, Bendels S, Bylund J, Chen K . Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 ( SMN2) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA). J Med Chem. 2018; 61(15):6501-6517. DOI: 10.1021/acs.jmedchem.8b00741. View

Turnbull J, Luther K . Patient satisfaction report paves way to improved care. QRC Advis. 1996; 13(1):1-7. View

10.

Pechmann A, Konig K, Bernert G, Schachtrup K, Schara U, Schorling D . SMArtCARE - A platform to collect real-life outcome data of patients with spinal muscular atrophy. Orphanet J Rare Dis. 2019; 14(1):18. PMC: 6341722. DOI: 10.1186/s13023-019-0998-4. View

11.

Cordts I, Deschauer M, Lingor P, Burian E, Baum T, Zimmer C . Radiation dose reduction for CT-guided intrathecal nusinersen administration in adult patients with spinal muscular atrophy. Sci Rep. 2020; 10(1):3406. PMC: 7042284. DOI: 10.1038/s41598-020-60240-x. View

12.

Oldenburg D, Guberina N, Stolte B, Kizina K, Stenzel E, Radbruch A . Radiation exposure of image-guided intrathecal administration of nusinersen to adult patients with spinal muscular atrophy. Neuroradiology. 2019; 61(5):565-574. DOI: 10.1007/s00234-019-02189-x. View

13.

Binz C, Schreiber-Katz O, Kumpe M, Ranxha G, Siegler H, Wieselmann G . An observational cohort study on impact, dimensions and outcome of perceived fatigue in adult 5q-spinal muscular atrophy patients receiving nusinersen treatment. J Neurol. 2020; 268(3):950-962. PMC: 7914247. DOI: 10.1007/s00415-020-10227-5. View

14.

Darras B . Spinal muscular atrophies. Pediatr Clin North Am. 2015; 62(3):743-66. DOI: 10.1016/j.pcl.2015.03.010. View

15.

Atkinson M, Kumar R, Cappelleri J, Hass S . Hierarchical construct validity of the treatment satisfaction questionnaire for medication (TSQM version II) among outpatient pharmacy consumers. Value Health. 2005; 8 Suppl 1:S9-S24. DOI: 10.1111/j.1524-4733.2005.00066.x. View

16.

Mercuri E, Darras B, Chiriboga C, Day J, Campbell C, Connolly A . Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy. N Engl J Med. 2018; 378(7):625-635. DOI: 10.1056/NEJMoa1710504. View

17.

Revicki D . Patient assessment of treatment satisfaction: methods and practical issues. Gut. 2004; 53 Suppl 4:iv40-4. PMC: 1867784. DOI: 10.1136/gut.2003.034322. View

18.

Montes J, McDermott M, Mirek E, Mazzone E, Main M, Glanzman A . Ambulatory function in spinal muscular atrophy: Age-related patterns of progression. PLoS One. 2018; 13(6):e0199657. PMC: 6019250. DOI: 10.1371/journal.pone.0199657. View

19.

Walter M, Wenninger S, Thiele S, Stauber J, Hiebeler M, Greckl E . Safety and Treatment Effects of Nusinersen in Longstanding Adult 5q-SMA Type 3 - A Prospective Observational Study. J Neuromuscul Dis. 2019; 6(4):453-465. PMC: 6918909. DOI: 10.3233/JND-190416. View

20.

Rio J, Porcel J, Tellez N, Sanchez-Betancourt A, Tintore M, Arevalo M . Factors related with treatment adherence to interferon beta and glatiramer acetate therapy in multiple sclerosis. Mult Scler. 2005; 11(3):306-9. DOI: 10.1191/1352458505ms1173oa. View