Improving quality, affordability, and equity of multiple sclerosis care.

OBJECTIVE: The prevailing approaches to selecting multiple sclerosis (MS) disease modifying therapies (DMTs) have contributed to exponential increases in societal expenditures and out-of-pocket expenses, without compelling evidence of improved outcomes. Guidance is lacking regarding when and in whom the benefits of preventing MS-related disability likely outweighs the risks of highly effective DMTs (HET) and when it is appropriate to consider DMT costs. Our objective was to develop a standardized approach to improve the quality, affordability and equity of MS care. METHODS: MS experts partnered with health plan pharmacists to develop an ethical, risk-stratified, cost-sensitive treatment algorithm. We developed a risk-stratification schema to classify patients with relapsing forms of MS as high, intermediate or low risk of disability based on the best available evidence and, when the evidence was poor or lacking, by consensus. DMTs are grouped as highly, modestly or low/uncertain effectiveness and preferentially ranked within groups by safety based on pre-specified criteria. We reviewed FDA documents and the published literature. When efficacy and safety are equivalent, the lower cost DMT is preferred. RESULTS: Assignment to the high-risk group prompts treatment with preferred HETs early in the disease course. For persons in the intermediate- or low-risk groups with cost or health care access barriers, we incorporated induction therapy with an affordable B-cell depleting agent. Based on more favorable safety profiles, our preferred approach prioritizes use of rituximab and natalizumab among HETs and interferon-betas or glatiramer acetate among modestly effective agents. INTERPRETATION: The risk-stratified treatment approach we recommend provides clear, measurable guidance in whom and when to prescribe HETs, when to prioritize lower cost DMTs and how to accommodate persons with MS with cost or other barriers to DMT use. It can be adapted to other cost structures and updated quickly as new information emerges. We recommend that physician groups partner with health insurance plans to adapt our approach to their settings, particularly in the United States. Future studies are needed to resolve the considerable uncertainty about how much variability in prognosis specific risk factors explain.

Vaccines and the risk of multiple sclerosis and other central nervous system demyelinating diseases.

IMPORTANCE: Because vaccinations are common, even a small increased risk of multiple sclerosis (MS) or other acquired central nervous system demyelinating syndromes (CNS ADS) could have a significant effect on public health. OBJECTIVE: To determine whether vaccines, particularly those for hepatitis B (HepB) and human papillomavirus (HPV), increase the risk of MS or other CNS ADS. DESIGN, SETTING, AND PARTICIPANTS: A nested case-control study was conducted using data obtained from the complete electronic health records of Kaiser Permanente Southern California (KPSC) members. Cases were identified through the KPSC CNS ADS cohort between 2008 and 2011, which included extensive review of medical records by an MS specialist. Five controls per case were matched on age, sex, and zip code. EXPOSURES: Vaccination of any type (particularly HepB and HPV) identified through the electronic vaccination records system. MAIN OUTCOMES AND MEASURES: All forms of CNS ADS were analyzed using conditional logistic regression adjusted for race/ethnicity, health care utilization, comorbid diseases, and infectious illnesses before symptom onset. RESULTS: We identified 780 incident cases of CNS ADS and 3885 controls; 92 cases and 459 controls were females aged 9 to 26 years, which is the indicated age range for HPV vaccination. There were no associations between HepB vaccination (odds ratio [OR], 1.12; 95% CI, 0.72-1.73), HPV vaccination (OR, 1.05; 95% CI, 0.62-1.78), or any vaccination (OR, 1.03; 95% CI, 0.86-1.22) and the risk of CNS ADS up to 3 years later. Vaccination of any type was associated with an increased risk of CNS ADS onset within the first 30 days after vaccination only in younger (<50 years) individuals (OR, 2.32; 95% CI, 1.18-4.57). CONCLUSIONS AND RELEVANCE: We found no longer-term association of vaccines with MS or any other CNS ADS, which argues against a causal association. The short-term increase in risk suggests that vaccines may accelerate the transition from subclinical to overt autoimmunity in patients with existing disease. Our findings support clinical anecdotes of CNS ADS symptom onset shortly after vaccination but do not suggest a need for a change in vaccine policy.

The incidence of clinically isolated syndrome in a multi-ethnic cohort.

The purpose of this study was to determine the incidence of clinically isolated syndrome (CIS), a potential precursor of multiple sclerosis (MS), and whether it varies by race/ethnicity in a multi-ethnic, population-based cohort. We conducted a retrospective cohort study of over 9 million person-years of observation from the multi-ethnic, community-dwelling members of Kaiser Permanente Southern California Health Plan from January 1, 2008 to December 31, 2010. Incidence of CIS and risk ratios comparing incidence rates between racial/ethnic groups were calculated using Poisson regression. We identified 468 newly diagnosed CIS cases that did not meet McDonald criteria for MS. The average age at diagnosis was 39.0 years (range 2.7-85.8) and 68.8% were women. The female preponderance was more pronounced among black (75.7%) and Hispanics (70.5%) than in white and Asian individuals with CIS (66.5 and 54.5%, respectively; P = 0.14). The most common presenting symptom in Hispanics was optic neuritis (P = 0.008), and in blacks, transverse myelitis (P = 0.07). Incidence of CIS was lower in Hispanics (3.8, 95% CI 3.2-4.4, P < 0.0001) and Asians (2.4, 95% CI 1.5-3.6, P < 0.0001) and similar in blacks (6.8, 95% CI 5.3-8.5, P = 0.30) compared with whites (5.9, 95% CI 5.1-6.7). The incidence of CIS varies by race/ethnicity and sex in a similar pattern to MS. In addition, the clinical presentation of CIS varies by race/ethnicity. These findings strengthen the probability that the old belief that blacks have a decreased risk of MS is no longer true. These findings highlight that studies that include minorities are likely to lead to important insights into the etiology and prognosis of CIS and MS.

Incidence of multiple sclerosis in multiple racial and ethnic groups.

OBJECTIVE: To determine whether the incidence of multiple sclerosis (MS) varies by race/ethnicity in a multiethnic, population-based cohort. METHODS: We conducted a retrospective cohort study of more than 9 million person-years of observation from the multiethnic, community-dwelling members of Kaiser Permanente Southern California health plan from January 1, 2008 to December 31, 2010. Incidence of MS and risk ratios comparing incidence rates between racial/ethnic groups were calculated using Poisson regression. RESULTS: We identified 496 patients newly diagnosed with MS who met McDonald criteria. The average age at diagnosis was 41.6 years (range 8.6-78.3 years) and 70.2% were women. The female preponderance was more pronounced among black (79.3%) than white, Hispanic, and Asian individuals with MS (67.8%, 68.1%, and 69.2%, respectively; p = 0.03). The incidence of MS was higher in blacks (10.2, 95% confidence interval [CI] 8.4-12.4; p < 0.0001) and lower in Hispanics (2.9, 95% CI 2.4-3.5; p < 0.0001) and Asians (1.4, 95% CI 0.7-2.4; p < 0.0001) than whites (6.9, 95% CI 6.1-7.8). Black women had a higher risk of MS (risk ratio 1.59, 95% CI 1.27-1.99; p = 0.0005) whereas black men had a similar risk of MS (risk ratio 1.04, 95% CI = 0.67-1.57) compared with whites. CONCLUSIONS: Our findings do not support the widely accepted assertion that blacks have a lower risk of MS than whites. A possible explanation for our findings is that people with darker skin tones have lower vitamin D levels and thereby an increased risk of MS, but this would not explain why Hispanics and Asians have a lower risk of MS than whites or why the higher risk of MS among blacks was found only among women.

Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome.

OBJECTIVE: To determine whether childhood obesity is a risk factor for developing pediatric multiple sclerosis (MS) or clinically isolated syndrome (CIS). METHODS: Cases were identified through the Kaiser Permanente Southern California (KPSC) pediatric acquired demyelinating diseases cohort between 2004 and 2010. For cases, body mass index (BMI) was obtained prior to symptom onset, for the underlying cohort BMI was obtained through the KPSC Children's health study (n = 913,097). Weight classes of normal weight, overweight, moderate obesity, and extreme obesity were assigned based on BMI specific for age and sex. RESULTS: We identified 75 newly diagnosed pediatric cases of MS or CIS, the majority of which were in girls (n = 41, 55%), age 11-18 (n = 54, 72%). Obesity was associated with a significantly increased risk of MS/CIS in girls (p = 0.005 for trend) but not in boys (p = 0.93). The adjusted odds ratio and 95% confidence intervals for CIS/MS among girls was 1.58 (0.71-3.50) for overweight compared to normal weight (reference category), 1.78 (0.70-4.49) for moderately obese, and 3.76 (1.54-9.16) for extremely obese. Moderately and extremely obese cases were more likely to present with transverse myelitis compared with normal/overweight children (p = 0.003). CONCLUSION: Our findings suggest the childhood obesity epidemic is likely to lead to increased morbidity from MS/CIS, particularly in adolescent girls.

Pediatric idiopathic intracranial hypertension and extreme childhood obesity.

OBJECTIVE: To estimate the magnitude of the association between overweight, moderate, and extreme childhood obesity and the risk of idiopathic intracranial hypertension (IIH). STUDY DESIGN: Risk estimates were obtained from the Kaiser Permanente Southern California Children's Health Study (n = 913 178). Weight classes were assigned by body mass index specific for age and sex. A combination of electronic database searches followed by complete medical records review was used to identify all children diagnosed with IIH between 2006 and 2009. RESULTS: We identified 78 children with IIH, the majority of whom were girls (n = 66, 84.5%), age 11-19 (n = 66, 84.5%), non-Hispanic Whites (n = 37, 47.4%), and overweight or obese (n = 57, 73.1%). The adjusted ORs and 95% CIs of IIH with increasing weight class were 1.00, 3.56 (1.72-7.39), 6.45 (3.10-13.44), and 16.14 (8.18-31.85) for underweight/normal weight (reference category), overweight, moderately obese and extremely obese 11-19 year olds, respectively (P for trend < .001). Other independent IIH risk factors included White non-Hispanic race/ethnicity for all age groups and female sex, but only in older children. Overweight/obese children also had more IIH symptoms at onset than normal weight children. CONCLUSIONS: We found that childhood obesity is strongly associated with an increased risk of pediatric IIH in adolescents. Our findings suggest that the childhood obesity epidemic is likely to lead to increased morbidity from IIH particularly among extremely obese, White non-Hispanic teenage girls. Our findings also suggest careful screening of these at risk individuals may lead to earlier detection and opportunity for treatment of IIH.