Mortality and comorbidities in patients with multiple sclerosis compared with a population without multiple sclerosis: An observational study using the US Department of Defense administrative claims database

Capkun, Gorana; Dahlke, Frank; Lahoz, Raquel; Nordstrom, Beth L.; Tilson, Hugh H.; Cutter, Gary; Bischof, Dorina; Moore, Alan; Simeone, Jason C; Fraeman, Kathy; Bancken, Fabrice; Geissbühler, Yvonne; Wagner, Michael R.; Cohan, Stanley

doi:10.1016/j.msard.2015.08.005

Cited by 98 publications

(98 citation statements)

References 29 publications

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“…Using the military British records (mostly males) proportional mortality ratios for MS in male members of the armed forces were found to be consistently elevated over 3 successive decades, 1979–2010, when compared to groups for each main social class and in other selected occupations [18]. Similarly, in a study by Capkun et al [17], a higher all-cause mortality was reported in those with MS (rate of 1.7–3.5-fold) when compared to a non-MS cohort, with 60.4% of the patients with MS who had received disease-modifying treatment in the past. A study that includes US-based individuals with MS, mortality risks were found to increase with age as well [17].…”

Section: Discussionmentioning

confidence: 95%

Multiple Sclerosis Mortality by Race/Ethnicity, Age, Sex, and Time Period in the United States, 1999–2015

et al. 2018

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Background: Multiple sclerosis (MS) carries high morbidity and shortens life span. While there is recent recognition of other US minority populations such as blacks and Hispanics being affected with MS, examination of MS-specific mortality trends by race/ethnicity has been lacking. Objective: To investigate MS mortality rates and trends in the United States by sex, age, and race/ethnicity. Methods: We used the Compressed Mortality data file for 1999–2015 in the Wide-ranging online Data for Epidemiological Research system developed by the Center for Disease Control and Prevention to calculate the age-adjusted (US 2000 standard population) and age-specific MS mortality rate (per 100,000) by race/ethnicity and sex over time. Five mutually exclusive racial/ethnic groups were included in the analysis: non-Hispanic (NH) white, NH black, NH Asian or Pacific Islander (API), NH American Indian or Alaska Native, and Hispanic. Results: The average annual age-adjusted MS mortality rate was highest among NH whites (0.90 for males and 1.50 for females) immediately followed by NH blacks (0.75 for males and 1.42 for females), and lowest among APIs (0.05 for males and 0.12 for females). Statistically significant, increasing trend in age-adjusted MS mortality was observed during 1999–2015 among NH whites and NH blacks regardless of sex, more substantially in the latter. Age-specific MS mortality patterns showed NH blacks had the highest rate under age 55 and NH whites had the highest rate after that age point. For these 2 groups, MS mortality increased with age in both sexes and peaked at ages 55–64 for NH blacks and 65–74 for NH whites before declining substantially, while for Hispanic and API groups the risk plateaued after age 55. Conclusion: MS-specific mortality trends demonstrate distinctive differences by race/ethnicity and age. The observations that whites and females are more likely to die from MS is in line with the overall understanding that these groups are affected more by MS. However, the findings of blacks dying at an earlier age and having more substantially increasing mortality trends than whites suggest that MS burden weighs unequally by race. Further investigation into these trends may provide additional evidence into risk or protective factors within each group.

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Section: Discussionmentioning

confidence: 95%

Multiple Sclerosis Mortality by Race/Ethnicity, Age, Sex, and Time Period in the United States, 1999–2015

et al. 2018

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“…Capkun et al. noted a slight decrease in melanoma rate among MS patients from a large sample, but do not report on melanoma risks among natalizumab‐treated MS patients 37. Another study reviewing incidence of cancer in MS (sampling 54,929 patients) concluded that melanoma rates were lower for people with MS compared to melanoma among the general population 26.…”

Section: Discussionmentioning

confidence: 99%

“…In interpreting our findings, several factors, particularly epidemiology of melanoma, natalizumab‐associated progressive multifocal leukoencephalopathy (PML), various aspects of the TOUCH Risk Management (RiskMAP) Action Plan, and the Safety Surveillance Program in this RiskMAP (Table 3), potential pathophysiology, and an overview of pharmacovigilance efforts for opportunistic complications of medications, should be considered 6, 7, 8, 9, 10, 11, 13, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple studies evaluated incidence of melanoma among MS patients, although none reported convincing epidemiologic or biologic associations or relative risk estimates 26, 27, 28, 37. Capkun et al.…”

Section: Discussionmentioning

confidence: 99%

“…Expression of α 4 β 1 integrin shows an inverse correlation with invasive potential of an aggressive melanoma cell line (B16) 30, 33. Expression of the integrin α 4 β 1 on melanoma cells can inhibit the invasive stage of melanoma 34, 37. Thus, there is a concern that an antibody such as natalizumab that binds to α 4 could directly promote at the cellular level melanoma cell replication, invasion, and migration.…”

Section: Discussionmentioning

confidence: 99%

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Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR)

et al. 2017

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A 43‐year‐old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against α4 integrins. To investigate the risk‐exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab‐associated melanoma reported to regulatory agencies. Data sources included the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) (2004–2014), a FDA Advisory Committee Meeting Report, and peer‐reviewed publications. In the United States, the manufacturer maintains an FDA‐mandated Tysabri Safety Surveillance Program (part of the Tysabri Outcomes Unified Commitment to Health (TOUCH)) of natalizumab‐treated patients. We statistically compared reporting completeness for natalizumab‐associated melanoma cases in FAERs for which information was obtained entirely from the TOUCH program versus cases where FAERS information was supplemented by TOUCH program information. FAERS included 137 natalizumab‐associated melanoma reports in patients with multiple sclerosis. Median age at melanoma diagnosis was 45 years (range: 21–74 years). Changes in preexisting nevi occurred in 16%, history of cutaneous nevi occurred in 22%, diagnosis within 2 years of beginning natalizumab occurred in 34%, and 74% had primary surgical treatment. Among seven natalizumab‐treated MS patients who developed biopsy‐confirmed melanoma on treatment and reported in the literature, median age at diagnosis was 41 years (range: 38–48 years); and the melanoma diagnosis occurred following a median of 12 natalizumab doses (range: 1–77 doses). A history of mole or nevi was noted in four patients and a history of prior melanoma was noted in one patient. Completeness scores for reports were significantly lower for FAERS cases reported from the TOUCH program versus FAERS cases supplemented by TOUCH information (median score of 2 vs. 4 items out of 8‐possible items, P < 0.0007). Clinicians should monitor existing nevi and maintain suspicion for melanoma developing in natalizumab‐treated patients. The TOUCH Safety Surveillance Program, currently focused on progressive multifocal leukoencephalopathy, should be expanded to include information on other serious complications including malignancies, particularly if they are immunologic in nature.

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Association Between Cigarette Smoking and Multiple Sclerosis

Rosso

Chitnis

2020

JAMA Neurol

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ultiple sclerosis (MS) is a chronic neurologic disorder characterized by demyelination and axonal loss in the central nervous system (CNS). 1 Environmental factors play a central role in the cause of MS. The most important environmental risk factors include cigarette smoking, Epstein-Barr virus infections, vitamin D deficiency, and obesity. 2,3 Cigarette smoking is a widespread habit with 2 billion consumers worldwide-a total of 5.8 trillion cigarettes are consumed each year. Smoking is associated with an increased risk of MS. Patients with MS have a worse long-term prognosis and greater rates of brain atrophy than their nonsmoking counterparts. 4 Also, smoking is more prevalent in patients with MS than in the general population. 5 Our review summarizes the current literature on the outcomes of cigarette smoking in patients with MS. We focus on how smoking affects the immune and nervous systems. We then comment on how these insights inform how smoking affects MS risk and prognosis. In addition, we outline the role of counseling and smoking cessation for patients with MS. MethodsWe conducted a narrative review by researching the available English-language literature studies. We used search terms including multiple sclerosis, cigarette smoking, passive smoking, tobacco, and waterpipe smoking. The literature review was performed using

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Mortality and comorbidities in patients with multiple sclerosis compared with a population without multiple sclerosis: An observational study using the US Department of Defense administrative claims database

Abstract: Rates of mortality and several comorbidities are higher in the MS versus non-MS cohort. Early recognition and management of comorbidities may reduce premature mortality and improve quality of life in patients with MS.

Cited by 98 publications

References 29 publications

Multiple Sclerosis Mortality by Race/Ethnicity, Age, Sex, and Time Period in the United States, 1999–2015

Multiple Sclerosis Mortality by Race/Ethnicity, Age, Sex, and Time Period in the United States, 1999–2015

Melanoma complicating treatment with natalizumab for multiple sclerosis: A report from the Southern Network on Adverse Reactions (SONAR)

Association Between Cigarette Smoking and Multiple Sclerosis

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