Decrease of natalizumab drug levels after switching from intravenous to subcutaneous administration in patients with multiple sclerosis.

BACKGROUND: Natalizumab is effective in the treatment of multiple sclerosis (MS). In 2021, the European Medicines Agency approved the subcutaneous (SC) variant of natalizumab which can be used instead of intravenous administration. However, the course of drug levels varies between administration routes, and the Food and Drug Administration rejected the request for approval of natalizumab SC for reasons that were not disclosed. Our objective was to evaluate the course of natalizumab trough drug levels in patients who switched from natalizumab intravenous to SC on various treatment intervals. METHODS: The NEXT-MS trial (N=382) investigates personalised treatment of natalizumab, in which infusion intervals are prolonged based on individual natalizumab trough drug levels. In 2021, an amendment was approved allowing participants to switch from intravenous to SC administration with frequent measurements of natalizumab drug levels and antidrug antibodies (ADAs). Results were compared with linear mixed model analyses. RESULTS: Until December 2022, 15 participants switched to SC natalizumab. Natalizumab drug levels with SC administration were on average 55% lower compared with intravenous administration (Exp (estimate) 0.45, 95% CI 0.39 to 0.53, p<0.001), leading to very low trough drug levels in three patients on extended treatment intervals. No natalizumab ADAs were detected during intravenous or SC treatment. None of the participants on natalizumab SC showed evidence of MS disease activity. CONCLUSIONS: Natalizumab trough drug levels can decrease after switching from natalizumab intravenous to SC administration. We advise to monitor trough drug levels in patients with low natalizumab drug levels during intravenous treatment, patients with higher body mass index or patients on extended treatment intervals who switch to SC administration of natalizumab.

Self-reported work productivity in people with multiple sclerosis and its association with mental and physical health.

PURPOSE: This study aimed to identify mental health, physical health, demographic and disease characteristics relating to work productivity in people with multiple sclerosis (MS). METHODS: In this cross-sectional study, 236 employed people with MS (median age = 42 years, 78.8% female) underwent neurological and neuropsychological assessments. Additionally, they completed questionnaires inquiring about work productivity (presenteeism: reduced productivity while working, and absenteeism: loss of productivity due to absence from work), mental and physical health, demographic and disease characteristics. Multiple linear and logistic regression analyses were performed with presenteeism and absenteeism as dependent variables, respectively. RESULTS: A model with mental and physical health factors significantly predicted presenteeism F(11,202) = 11.33, p < 0.001, R2 = 0.38; a higher cognitive (p < 0.001) and physical impact (p = 0.042) of fatigue were associated with more presenteeism. A model with only mental health factors significantly predicted absenteeism; χ2(11)=37.72, p < 0.001, with R2 = 0.27 (Nagelkerke) and R2 = 0.16 (Cox and Snell). Specifically, we observed that more symptoms of depression (p = 0.041) and a higher cognitive impact of fatigue (p = 0.011) were significantly associated with more absenteeism. CONCLUSIONS: In people with MS, both cognitive and physical impact of fatigue are positively related to presenteeism, while symptoms of depression and cognitive impact of fatigue are positively related to absenteeism.Implications for rehabilitationMultiple sclerosis (MS) affects people of working age, significantly interfering with work productivity.Higher cognitive and physical impact of fatigue were associated with more presenteeism in workers with MS.A higher cognitive impact of fatigue and more depressive symptoms were associated with absenteeism in workers with MS.Occupational and healthcare professionals should be aware of the impact of both physical and mental health on work productivity in workers with MS.

Cognitive functioning as a predictor of employment status in relapsing-remitting multiple sclerosis: a 2-year longitudinal study.

BACKGROUND: Cognitive functioning has been linked to employment outcomes in multiple sclerosis (MS) in cross-sectional studies. Longitudinal studies are however lacking and previous studies did not extensively examine executive functioning. OBJECTIVES: We examined whether baseline cognitive functioning predicts a change in employment status after 2 years, while taking into account mood, fatigue and disability level. METHODS: A total of 124 patients with relapsing-remitting MS (pwMS) and 60 healthy controls were included. They underwent neurological and neuropsychological examinations and completed online questionnaires. PwMS were divided into a stable and deteriorated employment status group (SES and DES), based on employment status 2 years after baseline. We first examined baseline differences between the SES and DES groups in cognitive functioning, mood, fatigue and disability level. A logistic regression analysis was performed, with change in employment status (SES/DES) as dependent variable. RESULTS: The DES group included 22% pwMS. Group differences were found in complex attention, executive functioning, self-reported cognitive functioning, fatigue and physical disability. More physical disability (OR = 1.90, p = 0.01) and lower executive functioning (OR = 0.30, p = 0.03) were retained as independent predictors of DES (R2 = 0.22, p ≤ 0.001). CONCLUSIONS: Baseline physical disability and executive functioning, but none of the other variables, moderately predicted a deterioration in employment status 2 years later. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. This study is registered at the Dutch CCMO register (https://www.toetsingonline.nl).

Postpartum stroke, a diagnostic challenge.

Postpartum stroke is rare, and because complaints are similar to preeclampsia, diagnostic confusion may delay the diagnostic workup that should include prompt computerized tomography of the brain. We describe a patient with postpartum stroke who died because of extensive ischemic damage throughout the brain with 3 simultaneous arterial occlusions. We stress the importance of raising this diagnosis in your workup because adequate measurements like angiography and intra-arterial thrombolysis could significantly improve the patient's outcome.

Prediction of intracranial metastases in cancer patients with headache.

BACKGROUND: The current study was conducted to investigate the diagnostic value of neurologic evaluation for the prediction of intracranial metastases in cancer patients with new or changed headache. METHODS: Between February 1997 and February 2000, general practitioners and specialists referred cancer patients with new or changed headache to the Department of Neurology at the study institution. All patients underwent a structured history and neurologic examination. Magnetic resonance imaging (MRI) of the brain was used as the gold standard for determining the presence of intracranial metastases. The association between baseline patient characteristics, history variables, and variables from the neurologic examination in patients with intracranial metastases was evaluated by univariate and multivariate logistic regression analyses in combination with receiver operating characteristic (ROC) curve analyses. RESULTS: Sixty-eight consecutive patients were included in the current study (48 females and 20 males). The mean age of the patients was 57 years (range, 24-88 years; standard deviation +/- 13.3 years). Breast carcinoma was the primary tumor in 32 patients (47.1%) and lung carcinoma was the primary tumor in 12 patients (17.6%). Intracranial metastases occurred in 22 patients (32.4%). The occurrence of intracranial metastases was predicted in the multivariate logistic regression analyses by one baseline patient characteristic variable and 2 history variables (i.e., headache duration of < or =10 weeks [odds ratio (OR) of 11.0; 95% confidence interval (95% CI), 1.1-108.2], emesis [OR of 4.0; 95% CI, 1.1-14.3], and pain not of tension- type [OR of 6.7; 95% CI, 1.8-25.1]). No variable from the neurologic examination was found to add information to the prediction model. When at least one of the three predictors was present, all patients with intracranial metastases could be identified with this prediction model. MRI could be omitted in 12 patients (26%) without intracranial metastases. The ROC area under curve of this model was 0.83. CONCLUSIONS: Intracranial metastases were found in 32.4% of the cancer patients with headache as the presenting symptom. Although 3 significant clinical predictors were found (headache duration < or =10 weeks, emesis, and pain not of tension- type), few patients could be excluded from undergoing MRI because of a low specificity. Therefore, MRI of the brain was considered to be warranted in all patients in the current study.