Effectiveness and safety of switching to teriflunomide in older patients with relapsing multiple sclerosis: A real-world retrospective multicenter analysis.

BACKGROUND: The prevalence of multiple sclerosis (MS) in older people is increasing due to population aging and availability of effective disease-modifying therapies (DMTs). Treating older people with MS is complicated by age-related and MS-related comorbidities, immunologic effects of prior DMTs, and immunosenescence. Teriflunomide is a once-daily oral immunomodulator that has demonstrated efficacy and acceptable safety in clinical trials of adults with relapsing forms of MS (RMS). However, there are limited clinical trial and real-world data regarding teriflunomide use in people with MS aged >55 years. We analyzed real-world data to assess the effectiveness and safety of teriflunomide in older people with RMS who had switched to this agent from other DMTs. METHODS: People with RMS (relapsing remitting and active secondary progressive MS) aged ≥55 years who had switched from other DMTs to teriflunomide (7 mg or 14 mg) for ≥1 year were identified retrospectively by chart review at four sites in the United States. Data were extracted from medical records from 1 year pre-index to 2 years post-index (index defined as the teriflunomide start date). Assessments of effectiveness included annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging (MRI) outcomes. Assessments of safety included lymphocyte counts, infections, and malignancies. We examined the effectiveness outcomes and lymphocyte counts within sub-groups defined by age (55-64, ≥65 years), sex, MS type, and prior route of DMT administration (oral, injectable, infusible). RESULTS: In total, 182 patients with RMS aged ≥55 years who switched from other DMTs to teriflunomide were identified (mean [SD] age: 62.5 [5.4] years). Mean ARR decreased from the start of teriflunomide treatment (mean [SD]: 0.43 [0.61]) to year 1 post-index (0.13 [0.65]) and year 2 post-index (0.05 [0.28]). Mean EDSS score remained unchanged from index (mean [SD]: 4.5 [1.8]) to 1 year post-treatment (4.5 [1.8]) and increased slightly at 2 years post-treatment (4.7 [1.7]). MRI scans from index and years 1 and 2 post-index compared with scans from the previous year indicated that most patients had stable or improved MRI outcomes at index (87.7%) and remained stable or improved at years 1 (96.0%) and 2 (93.6%). Lymphopenia decreased at years 1 (21.4%) and 2 post-index (14.8%, compared to index (23.5%). By 1 year post-index, fewer patients had grade 3 or 4 lymphopenia, and at 2 years post-index, there were no patients with grade 3 or 4 lymphopenia. Infection incidence was low (n = 40, 22.0%) and none were related to teriflunomide. The decreases in lymphopenia were driven by decreases among people who switched from a prior oral DMT; there were no notable differences in lymphopenia across the other sub-groups examined. ARR, EDSS score, and MRI outcomes across all sub-groups were similar to the results of the overall population. CONCLUSION: Our multicenter, longitudinal, retrospective study demonstrated that patients with RMS aged 55 or older switching to teriflunomide from other DMTs had significantly improved ARR, stable disability, and stable or improved MRI over up to 2 years' follow up. Safety results were acceptable with fewer patients exhibiting lymphopenia at years 1 and 2 post-index.

Vitamin B(12) deficiency and incontinence: is there an association?

BACKGROUND: This study investigated the relationship between B(12) (cobalamin) levels and incontinence in older outpatients using secondary data analysis. METHODS: Between 1991 and 1999, there were 929 patients (258 men and 671 women) for whom urinary incontinence (UI), fecal incontinence (FI), and B(12) were prospectively recorded. Covariates included race, gender, age, medications, Mini-Mental State Examination, modified illness rating, and instrumental activities of daily living (IADLs). RESULTS: Some form of incontinence (UI or FI or both) was found in 41% of subjects, isolated UI in 34%, double incontinence (DI) in 12%, and isolated FI in 4%. Having UI increased the risk of also having FI (p <.0001). Serum B(12) levels of 300 pg/ml or less were not predictive of isolated UI or isolated FI. However, in logistic regression, DI was predicted by B(12) (odds ratio [OR] = 2.113, p =.0094), IADLs (OR = 0.810, p <.0001), cathartics/laxative use (OR = 1.902, p =.126), and diuretic use (OR = 2.226, p =.006). Considering isolated UI in women, higher IADLs reduced risk of UI (OR = 0.956, p =.002), while diuretics (OR = 1.481, p =.041) and antihistamines (OR = 1.909, p =.046) both increased risk of UI. In men, only use of anticonvulsant medications (OR = 4.529, p =.023) increased risk of isolated UI. Greater physical illness in both genders increased risk of isolated FI (OR = 1.204, p =.006). CONCLUSIONS: These findings suggest that serum B(12) at levels of 300 pg/ml or less are not associated with isolated UI or isolated FI but may play a role in DI. A possible association of low B(12) levels with DI is intriguing because of the implications for treatment and prevention. More immediately, medication side effects should be considered when evaluating this problem.