ABSTRACT
BACKGROUND: Therapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing-remitting MS, whereas few therapies are available for progressive forms of MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape. METHODS: We conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients. According to the retrospective study framework, data was acquired at prespecified time points. Clinical readouts were assessed every three months. Disease progression was determined as increase in expanded disability status scale (EDSS), radiological progression, or the occurrence of new relapses under treatment. For safety analyses, adverse events (AE) and reasons for discontinuation were documented. The collected data points were analyzed at baseline and after 6, 12 and 18 months. However, data were predominately collected at the 6- and 12-month time points as many patients were lost to follow-up. In a group consisting of 41 patients, a more detailed investigation regarding disease progression was conducted, including data from measurement of cognitive and motoric functions. RESULTS: Under siponimod therapy, 64.8% of patients experienced sustained clinical disease stability at 12 months. Out of the stable patients 21.4% of patients improved. Of the remaining patients, 31.5% experienced EDSS progression, 3.7% worsened without meeting the threshold for progression. Relapses occurred in 7.4%. Radiological disease activity was detected in 24.1% of patients after six months of treatment and in 29.6% of patients at 12 months follow-up. The in-depth cohort consisting of 41 patients demonstrated no substantial changes in cognitive abilities measured by Paced Auditory Serial Addition Test and Symbol Digit Modalities Test or motoric functions measured with Timed 25-Foot Walk, 100-m timed test, and 9-Hole Peg Test throughout the 12-month study period. Radiological assessment showed a stable volume of white and grey matter, as well as a stable lesion count at 12 months follow-up. AE were observed in nearly half of the included patients, with lymphopenia being the most common. Due to disease progression or AE, 31.2% of patients discontinued therapy. CONCLUSION: Treatment with siponimod had an overall stabilizing effect regarding clinical and radiological outcome measures. However, there is a need for more intensive treatment management and monitoring to identify disease progression and AE.
ABSTRACT
In patients with anti-Yo associated paraneoplastic cerebellar degeneration (PCD) neurological symptoms precede the diagnosis of the underlying cancer in about 60%. Ovarian carcinoma, breast cancer and other gynaecological malignancies are most frequently found as causative malignancies. Antitumour treatment should be applied in an early stage of disease. The identification of the tumour is a diagnostic challenge in many of these patients. In the first of two patients reported here a pelvic tumour was suggested after detection of a pathological lymph node and elevated tumour markers. The intraoperative findings appeared macroscopically normal during ovariectomy with adnexectomy. Not until microscopic examination of the resected tissue was performed was a tubal adenocarcinoma found. If intrapelvic gynaecological tumours are suspected a deliberate surgical exploration seems to be justified, but only after an intensive diagnostic investigation. To search for the underlying cancer in patients with paraneoplastic neurological disorders successive CT and [18F]-FDG-PET are widely recommended. Instead of this in the second reported patient whole-body dual-modality PET/CT was performed revealing enhanced uptake in three regions of the left thorax. By combining function and anatomy PET/CT was able to localise the lesions and characterise them as lymph node metastases of breast cancer. Diagnosis could be confirmed by subsequently executed needle biopsy. PET/CT seems to be highly applicable in the investigation of paraneoplastic disorders with unknown primary cancer. It may help in guidance of needle biopsy or to optimise the results of deliberate surgery and it provides whole-body tumour staging in a single session with higher diagnostic accuracy than PET alone.
