INTRODUCTION: In clinical trials of alemtuzumab, autoimmune thyroid adverse events (AEs) were frequent. Here, we assess the impact of thyroid AEs on health-related quality of life (HRQL) in alemtuzumab-treated patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: In phase 3 CARE-MS I (NCT00530348) and II (NCT00548405) trials, patients with RRMS were administered alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Patients could participate in an extension study (NCT00930553) through year 6. HRQL was assessed at baseline and annually using the Functional Assessment of Multiple Sclerosis (FAMS), EuroQoL-5 Dimension Visual Analog Scale (EQ-5D VAS), and 36-Item Short-Form Survey (SF-36) questionnaires. Outcomes were analyzed in patients with or without thyroid AEs (nonserious or serious). A subset of patients with thyroid AEs was analyzed to assess HRQL before and during the onset of thyroid AEs. RESULTS: A total of 811 CARE-MS patients were treated with alemtuzumab. Of these, 342 (42%) patients experienced thyroid AEs over 6 years; serious thyroid AEs occurred in 44 (5%) patients. At year 6, HRQL outcomes generally remained slightly improved or similar to core study baseline in alemtuzumab-treated patients with or without thyroid AEs: FAMS (least-squares mean change from baseline without thyroid AEs, 0.7; with nonserious thyroid AEs, 5.1; with serious thyroid AEs, - 5.3), EQ-5D VAS (2.0; 3.0; - 6.8), SF-36 mental component summary (MCS [0.6; 1.6; - 2.8]), SF-36 physical component summary (PCS [0.8; 1.0; 1.1]). Over 6 years, 63-82% of patients in each group had improved/stable SF-36 MCS and PCS scores. Among patients with thyroid AE onset in year 3 (peak incidence), there were minimal differences between HRQL outcomes before onset (year 2) and after onset (year 3). CONCLUSION: Autoimmune thyroid AEs (serious and nonserious) had minimal impact on HRQL in alemtuzumab-treated patients. These data may aid therapeutic decisions in patients with relapsing MS.

This study looked at alemtuzumab, an approved treatment for multiple sclerosis (MS). People who receive alemtuzumab may develop thyroid problems. The researchers wanted to know whether people who developed thyroid problems with alemtuzumab had a worse quality of life compared with those who did not. The researchers measured quality of life using a questionnaire. The questionnaire looked at people’s physical, social, and psychological well-being over 6 years. A total of 811 people with MS treated with alemtuzumab took part in this study. Of these, 469 people (58%) did not develop thyroid problems and 342 people (42%) developed thyroid problems. The thyroid problems were serious in 44 people. The researchers observed that thyroid problems during alemtuzumab treatment did not make quality of life worse in most people. Some people with serious thyroid problems had worsened quality of life; this was mostly among people who required certain treatments for their thyroid problems. Quality of life did not change much in people while the thyroid problems were ongoing. This study shows that thyroid problems after alemtuzumab treatment for MS have little negative impact on quality of life for most people. These findings may help healthcare providers make decisions about MS treatment.

1st Medical Faculty Charles University Prague Czech Republic

1st Neurology Department Aeginition Hospital National and Kapodistrian University of Athens Athens Greece

Advanced Neurology of Colorado Fort Collins CO USA

Advanced Neurosciences Institute Franklin TN USA

Center of Clinical Neuroscience Carl Gustav Carus University Hospital Dresden Germany

Hospital Universitario Quirónsalud Madrid Madrid Spain

Medical Neuroscience Cluster Medical University of Vienna Vienna Austria

MS Center for Innovations in Care Missouri Baptist Medical Center St Louis MO USA

Neurology Associates Maitland FL USA

Oslo University Hospital Ullevål and Institute of Clinical Medicine University of Oslo Oslo Norway

Sanofi Cambridge MA USA

SCDO Neurologia CRESM University Hospital San Luigi Gonzaga Orbassano Turin Italy

University of Alberta Edmonton AB Canada

University Vita Salute San Raffaele Milan Italy

Vithas Nisa Hospital Seville Spain

Zobrazit více v PubMed

Berger JR. Functional improvement and symptom management in multiple sclerosis: clinical efficacy of current therapies. Am J Manag Care. 2011;17(Suppl 5):S146–S153. PubMed

Sorensen PS. Balancing the benefits and risks of disease-modifying therapy in patients with multiple sclerosis. J Neurol Sci. 2011;311(Suppl 1):S29–S34. doi: 10.1016/S0022-510X(11)70006-5. PubMed DOI

Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1819–1828. doi: 10.1016/S0140-6736(12)61769-3. PubMed DOI

Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1829–1839. doi: 10.1016/S0140-6736(12)61768-1. PubMed DOI

Fox EJ, Brassat D, Alroughani R, et al. Alemtuzumab provides durable efficacy over 6 years in patients with active relapsing-remitting multiple scle.rosis and an inadequate response to prior therapy in the absence of continuous treatment (CARE-MS II) Neurology. 2017;88(Suppl 16):S24.006.

Singer B, Coles AJ, Boyko AN, et al. Improvements in clinical outcomes with alemtuzumab in treatment-naive patients with active relapsing-remitting multiple sclerosis are durable over 6 years in the absence of continuous treatment (CARE-MS I) Neurology. 2017;88(Suppl 16):S24.005.

Arroyo Gonzalez R, Kita M, Crayton H, et al. Alemtuzumab improves quality-of-life outcomes compared with subcutaneous interferon beta-1a in patients with active relapsing-remitting multiple sclerosis. Mult Scler. 2017;23(10):1367–1376. doi: 10.1177/1352458516677589. PubMed DOI

Arroyo R, Bury DP, Guo JD, et al. Impact of alemtuzumab on health-related quality of life over 6 years in CARE-MS II trial extension patients with relapsing-remitting multiple sclerosis. Mult Scler. 2019 doi: 10.1177/1352458519849796. PubMed DOI PMC

Arroyo Gonzalez R, Guo J, Zhang W, et al. Alemtuzumab improves patient-reported quality of life outcomes in patients with relapsing-remitting multiple sclerosis: results from the CARE-MS I extension study. Neurology. 2018;90(P6):380. PubMed

Coles AJ, Cohen JA, Fox EJ, et al. Alemtuzumab CARE-MS II 5-year follow-up: efficacy and safety findings. Neurology. 2017;89(11):1117–1126. doi: 10.1212/WNL.0000000000004354. PubMed DOI PMC

LEMTRADA® (alemtuzumab) [Prescribing Information] 2019. Cambridge: Genzyme Corporation.

Havrdova E, Arnold DL, Cohen JA, et al. Alemtuzumab CARE-MS I 5-year follow-up: durable efficacy in the absence of continuous MS therapy. Neurology. 2017;89(11):1107–1116. doi: 10.1212/WNL.0000000000004313. PubMed DOI PMC

LEMTRADA [Summary of Product Characteristics] April 2019. Diegem: Sanofi Belgium.

Twyman C, Oyuela P, Palmer J, Margolin D, Dayan C. Thyroid autoimmune adverse events in patients treated with alemtuzumab for relapsing-remitting multiple sclerosis: four-year follow-up of the CARE-MS studies. Neurology. 2014;82(P2):199.

Devonshire V, Phillips R, Wass H, Da Roza G, Senior P. Monitoring and management of autoimmunity in multiple sclerosis patients treated with alemtuzumab: practical recommendations. J Neurol. 2018;265(11):2494–2505. doi: 10.1007/s00415-018-8822-y. PubMed DOI PMC

Decallonne B, Bartholome E, Delvaux V, et al. Thyroid disorders in alemtuzumab-treated multiple sclerosis patients: a Belgian consensus on diagnosis and management. Acta Neurol Belg. 2018;118(2):153–159. doi: 10.1007/s13760-018-0883-2. PubMed DOI PMC

Cancer Therapy Evaluation Program. Common terminology criteria for adverse events v3.0 (CTCAE). National Cancer Institute; [updated 2006 Aug 9; cited 2020 Feb 4]. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf.

Cella DF, Dineen K, Arnason B, et al. 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. PubMed DOI

Brooks R. EuroQol: the current state of play. Health Policy. 1996;37(1):53–72. doi: 10.1016/0168-8510(96)00822-6. PubMed DOI

Ware JE, Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30(6):473–483. doi: 10.1097/00005650-199206000-00002. PubMed DOI

Ware JE, Jr, Kosinski M, Bjorner JB, Turner-Bowker DM, Gandek B, Maruish ME. User’s Manual for the 36v2® Health Survey. 2. Lincoln: Quality Metric; 2007.

Rudick RA, Miller D, Hass S, et al. Health-related quality of life in multiple sclerosis: effects of natalizumab. Ann Neurol. 2007;62(4):335–346. doi: 10.1002/ana.21163. PubMed DOI

Stahlman S, Oh GT. Thyroid disorders, active component, U.S. Armed Forces, 2008–2017. MSMR. 2018;25(12):2–9. PubMed

Khattak RM, Ittermann T, Nauck M, Below H, Volzke H. Monitoring the prevalence of thyroid disorders in the adult population of Northeast Germany. Popul Health Metr. 2016;14:39. doi: 10.1186/s12963-016-0111-3. PubMed DOI PMC

Shivaprasad C, Boppana R, Kolly A, Pullikal A, Goel A, Dwarkanath C. Impairment of health-related quality of life among Indian patients with hypothyroidism. Indian J Endocrinol Metab. 2018;22(3):335–338. doi: 10.4103/ijem.IJEM_702_17. PubMed DOI PMC

Elberling TV, Rasmussen AK, Feldt-Rasmussen U, Hording M, Perrild H, Waldemar G. Impaired health-related quality of life in Graves’ disease. A prospective study. Eur J Endocrinol. 2004;151(5):549–555. doi: 10.1530/eje.0.1510549. PubMed DOI

Riazi A, Hobart J, Lamping D, et al. Using the SF-36 measure to compare the health impact of multiple sclerosis and Parkinson’s disease with normal population health profiles. J Neurol Neurosurg Psychiatry. 2003;74(6):710–714. doi: 10.1136/jnnp.74.6.710. PubMed DOI PMC

Endocrine and multiple sclerosis outcomes in patients with autoimmune thyroid events in the alemtuzumab CARE-MS studies