Adherence, satisfaction and functional health status among patients with multiple sclerosis using the BETACONNECT® autoinjector: a prospective observational cohort study

Ingo Kleiter, Michael Lang, Judith Jeske, Christiane Norenberg, Barbara Stollfuß, Markus Schürks, Ingo Kleiter, Michael Lang, Judith Jeske, Christiane Norenberg, Barbara Stollfuß, Markus Schürks

Abstract

Background: Maintaining patient adherence to disease modifying drugs in multiple sclerosis is a challenge, which can be improved by autoinjectors. The BETACONNECT® is a fully electronic autoinjector for the injection of interferon beta-1b (IFN beta-1b) automatically recording injections.

Methods: The BETAEVAL study was a prospective, observational, cohort study over 24 weeks among patients with relapsing remitting multiple sclerosis or clinically isolated syndrome treated with IFN beta-1b in Germany using the BETACONNECT®. The primary aim was to investigate treatment adherence, secondary aims included assessing satisfaction and functional health status. Adherence was evaluated from injection data recorded by the device. Patient-related data were obtained from clinical examinations and patient questionnaires.

Results: Of the 151 patients enrolled, 143 were available for analysis. Thirty-four patients discontinued the study prematurely. 107/143 (74.8%) patients still used the BETACONNECT® at the end of the study. Injection data from the device at any visit was available for 107 patients. Among those, the percentage of adherent patients injecting ≥80% of doses and still participating in the study was 57.9% at week 24. 29% of patients prematurely stopped the study, 13.1% injected <80%. Among patients with BETACONNECT® data at the respective visit, the proportion of adherent patients was high over the entire study period (week 4: 81.1% [N = 95], week 12: 86.7% [N = 83], week 24: 80.5% [N = 77]). Participants (N = 143) indicated high satisfaction with the BETACONNECT®. At week 24, 98.0% of patients who completed the corresponding questionnaire (strongly) agreed that it was user-friendly, 81.2% felt confident in using it compared to their previous way and 85.5% preferred it to their previous way of injection. Injection-related pain was rated as mild to moderate at all follow-up visits. Whereas 17.2% of patients with corresponding questionnaire indicated using analgesics prior to injection at week 4, only 9.1% did at week 24. Outcomes from questionnaires assessing functional health status, depression, fatigue and cognitive function were very similar throughout the study course.

Conclusions: The majority of patients continued using the BETACONNECT® for IFN beta-1b treatment during the 24-week study period. Adherence was high among participants still using the BETACONNECT® and patients were highly satisfied with the device. Ongoing studies will evaluate long-term adherence and treatment outcomes in patients using the BETACONNECT®.

Trial registration: clinicaltrails.gov NCT02121444 (registered April 22, 2014).

Keywords: Adherence; Autoinjector; BETACONNECT®; Compliance; Disease modifying drugs; Interferon beta-1b; Multiple sclerosis; Persistence; Satisfaction.

Conflict of interest statement

Ethics approval and consent to participate

The BETAEVAL study was approved by the ethics committee “Ethikkommission der Medizinischen Fakultät der Ruhr Universität Bochum”; registration number 4837–13. All participants provided written informed consent to participate in the study.

Consent for publication

Not applicable.

Competing interests

IK received honoraria for consultancy or speaking from Biogen, Chugai, Roche and Shire, travel reimbursement from Bayer Healthcare and grant support from Affectis, Chugai and Diamed, none related to this manuscript and honoraria for consultancy from Bayer Healthcare, related to this manuscript.

ML has received travel grants, speaker’s honoraria, financial research support and consultancy fees from Teva, Merck Serono, Sanofi-Genzyme, Novartis, Bayer, Biogen.

JJ has received speaker’s honoraria and financial research support from Bayer, Novartis, Biogen and Sanofi-Genzyme.

CN is an employee of Bayer AG, Wuppertal, Germany.

BS is an employee of Bayer Vital GmbH, Leverkusen, Germany.

MS is an employee of Bayer Vital GmbH, Leverkusen, Germany. He previously served as an associate editor to BMC Neurology.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart describing patient disposition in the BETAEVAL study. FU follow-up; AE adverse events; FAS full analysis set; SAF safety analysis set
Fig. 2
Fig. 2
a: all patients with any BETACONNECT® reading; b: patients already on interferon-beta 1b; c: patients without previous interferon-beta 1b treatment
Fig. 3
Fig. 3
a Adherence and b: compliance (percentage of injections administered) among patients with BETACONNECT® data at respective visit
Fig. 4
Fig. 4
Evaluation of the BETACONNECT®

References

    1. Petersen G, Wittmann R, Arndt V, Gopffarth D. Epidemiology of multiple sclerosis in Germany: regional differences and drug prescription in the claims data of the statutory health insurance. Nervenarzt. 2014;85(8):990–998. doi: 10.1007/s00115-014-4097-4.
    1. Al-Sabbagh A. Medication gaps in disease-modifying drug therapy for multiple sclerosis are associated with an icreased risk of relapse: findings from a national manged care database. J Neurol. 2008;255(Suppl. 2):S.79.
    1. Tremlett H, Van der Mei I, Pittas F, Blizzard L, Paley G, Dwyer T, Taylor B, Ponsonby AL. Adherence to the immunomodulatory drugs for multiple sclerosis: contrasting factors affect stopping drug and missing doses. Pharmacoepidemiol Drug Saf. 2008;17(6):565–576. doi: 10.1002/pds.1593.
    1. Ivanova JI, Bergman RE, Birnbaum HG, Phillips AL, Stewart M, Meletiche DM. Impact of medication adherence to disease-modifying drugs on severe relapse, and direct and indirect costs among employees with multiple sclerosis in the US. J Med Econ. 2012;15(3):601–609. doi: 10.3111/13696998.2012.667027.
    1. Steinberg SC, Faris RJ, Chang CF, Chan A, Tankersley MA. Impact of adherence to interferons in the treatment of multiple sclerosis: a non-experimental, retrospective, cohort study. Clin Drug Investig. 2010;30(2):89–100. doi: 10.2165/11533330-000000000-00000.
    1. Hansen K, Schussel K, Kieble M, Werning J, Schulz M, Friis R, Pohlau D, Schmitz N, Kugler J. Adherence to disease modifying drugs among patients with multiple sclerosis in Germany: a retrospective cohort study. PLoS One. 2015;10(7):e0133279. doi: 10.1371/journal.pone.0133279.
    1. Devonshire V, Lapierre Y, Macdonell R, Ramo-Tello C, Patti F, Fontoura P, Suchet L, Hyde R, Balla I, Frohman EM, et al. The Global Adherence Project (GAP): a multicenter observational study on adherence to disease-modifying therapies in patients with relapsing-remitting multiple sclerosis. Eur J Neurol. 2011;18(1):69–77. doi: 10.1111/j.1468-1331.2010.03110.x.
    1. Lugaresi A, Rottoli MR, Patti F. Fostering adherence to injectable disease-modifying therapies in multiple sclerosis. Expert Rev Neurother. 2014;14(9):1029–1042. doi: 10.1586/14737175.2014.945523.
    1. Brochet B, Lemaire G, Beddiaf A, et l'Epicure Study G Reduction of injection site reactions in multiple sclerosis (MS) patients newly started on interferon beta 1b therapy with two different devices. Rev Neurol (Paris) 2006;162(6–7):735–740. doi: 10.1016/S0035-3787(06)75071-8.
    1. Lugaresi A. RebiSmart (version 1.5) device for multiple sclerosis treatment delivery and adherence. Expert Opin Drug Deliv. 2013;10(2):273–283. doi: 10.1517/17425247.2013.746311.
    1. Ziemssen T, Sylvester L, Rametta M, Ross AP. Patient satisfaction with the new interferon Beta-1b autoinjector (BETACONNECT) Neurol Ther. 2015;4(2):125–136. doi: 10.1007/s40120-015-0036-y.
    1. Fachinformation Betaferon® 250 μg/ml. Bayer Vital GmbH, Leverkusen. März 2017.
    1. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS) Neurology. 1983;33(11):1444–1452. doi: 10.1212/WNL.33.11.1444.
    1. Smith A. Symbol digit modalities test: manual. Los Angeles: Wetern Psychological Services; 1982.
    1. Cella DF, Dineen K, Arnason B, Reder A, Webster KA, Karabatsos G, Chang C, Lloyd S, Steward J, Stefoski D. Validation of the functional assessment of multiple sclerosis quality of life instrument. Neurology. 1996;47(1):129–139. doi: 10.1212/WNL.47.1.129.
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x.
    1. Radloff L. The CES-D scale: a self-report depressive scale for research in the general population. J Appl Psychol Meas. 1977;1:385–401. doi: 10.1177/014662167700100306.
    1. Penner IK, Raselli C, Stocklin M, Opwis K, Kappos L, Calabrese P. The Fatigue Scale for Motor and Cognitive Functions (FSMC): validation of a new instrument to assess multiple sclerosis-related fatigue. Mult Scler. 2009;15(12):1509–1517. doi: 10.1177/1352458509348519.
    1. Reese JP, Wienemann G, John A, Linnemann A, Balzer-Geldsetzer M, Mueller UO, Eienbroker C, Tackenberg B, Dodel R. Preference-based health status in a German outpatient cohort with multiple sclerosis. Health Qual Life Outcomes. 2013;11:162. doi: 10.1186/1477-7525-11-162.
    1. Patti F, Russo P, Pappalardo A, Macchia F, Civalleri L, Paolillo A, group Fs Predictors of quality of life among patients with multiple sclerosis: an Italian cross-sectional study. J Neurol Sci. 2007;252(2):121–129. doi: 10.1016/j.jns.2006.10.017.
    1. Pozzilli C, Schweikert B, Ecari U, Oentrich W, Bugge JP. Quality of life and depression in multiple sclerosis patients: longitudinal results of the BetaPlus study. J Neurol. 2012;259(11):2319–2328. doi: 10.1007/s00415-012-6492-8.
    1. Kunkel A, Fischer M, Faiss J, Dahne D, Kohler W, Faiss JH. Impact of natalizumab treatment on fatigue, mood, and aspects of cognition in relapsing-remitting multiple sclerosis. Front Neurol. 2015;6:97. doi: 10.3389/fneur.2015.00097.
    1. Jones KH, Jones PA, Middleton RM, Ford DV, Tuite-Dalton K, Lockhart-Jones H, Peng J, Lyons RA, John A, Noble JG. Physical disability, anxiety and depression in people with MS: an internet-based survey via the UK MS register. PLoS One. 2014;9(8):e104604. doi: 10.1371/journal.pone.0104604.
    1. Ensari I, Motl RW, McAuley E, Mullen SP, Feinstein A. Patterns and predictors of naturally occurring change in depressive symptoms over a 30-month period in multiple sclerosis. Mult Scler. 2014;20(5):602–609. doi: 10.1177/1352458513504251.
    1. Parmenter BA, Weinstock-Guttman B, Garg N, Munschauer F, Benedict RH. Screening for cognitive impairment in multiple sclerosis using the symbol digit modalities test. Mult Scler. 2007;13(1):52–57. doi: 10.1177/1352458506070750.
    1. Devonshire V, Feinstein A, Gillet A. Treatment, adherence, Paersistence, and compliance of patients using the RebiSmart® auto-injector. 96-weeks results. Poster presentation at the 68th annual meeting of the American Academy of Neurology. 2016; poster P3.037. 2016.
    1. Strober LB, Rao SM, Lee JC, Fischer E, Rudick R. Cognitive impairment in multiple sclerosis: an 18 year follow-up study. Mult Scler Relat Disord. 2014;3(4):473–481. doi: 10.1016/j.msard.2014.03.004.
    1. Willis H, Webster J, Larkin AM, Parkes L. An observational, retrospective, UK and Ireland audit of patient adherence to subcutaneous interferon beta-1a injections using the RebiSmart((R)) injection device. Patient Prefer Adherence. 2014;8:843–851. doi: 10.2147/PPA.S54986.
    1. Fernandez O, Arroyo R, Martinez-Yelamos S, Marco M, Merino JA, Munoz D, Merino E, Roque A, Group RS Long-term adherence to IFN Beta-1a treatment when using RebiSmart(R) device in patients with relapsing-remitting multiple sclerosis. PLoS One. 2016;11(8):e0160313. doi: 10.1371/journal.pone.0160313.
    1. Lugaresi A, Florio C, Brescia-Morra V, Cottone S, Bellantonio P, Clerico M, Centonze D, Uccelli A, di Ioia M, De Luca G, et al. Patient adherence to and tolerability of self-administered interferon beta-1a using an electronic autoinjection device: a multicentre, open-label, phase IV study. BMC Neurol. 2012;12:7. doi: 10.1186/1471-2377-12-7.
    1. Lugaresi A, De Robertis F, Clerico M, Brescia Morra V, Centonze D, Borghesan S, Maniscalco GT, group Rs Long-term adherence of patients with relapsing-remitting multiple sclerosis to subcutaneous self-injections of interferon beta-1a using an electronic device: the RIVER study. Expert Opin Drug Deliv. 2016;13(7):931–935. doi: 10.1517/17425247.2016.1148029.
    1. Devonshire VA, Feinstein A, Moriarty P. Adherence to interferon beta-1a therapy using an electronic self-injector in multiple sclerosis: a multicentre, single-arm, observational, phase IV study. BMC Res Notes. 2016;9:148. doi: 10.1186/s13104-016-1948-z.
    1. Rieckmann P, Schwab M, Pöhlau D, Wagner T, Schel E, Bayas A. Adherence to subcutaneous IFN-b1a - final analysis of the non-interventional study READOUTsmart using the dosing log and readout function of RebiSmart®. Poster presentation at the annual meeting of the American Academy of Neurology 2016. P3.098. 2016.
    1. Evaluation of Potential Predictors of Adherence by Investigating a Representative Cohort of Multiple Sclerosis (MS) Patients in Germany Treated With Betaferon (BETAPREDICT). Identifier: NCT02486640. . Accessed 1 Sept 2017.

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