Potential risk of disease modifying therapies on neoplasm development and coadjutant factors in multiple sclerosis outpatients

Abstract

Neoplasm development in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) has been widely discussed. The aim of this work is to determine neoplasm frequency, relationship with the prescription pattern of DMTs, and influence of the patients’ baseline characteristics. Data from 250 MS outpatients were collected during the period 1981–2019 from the medical records of the Neurology Service of the HUPM (Hospital Universitario Puerta del Mar)—in Southern Spain—and analysed using Cox models. Neoplasm prevalence was 24%, mainly located on the skin, with cancer prevalence as expected for MS (6.8%). Latency period from MS onset to neoplasm diagnosis was 10.4 ± 6.9 years (median 9.30 [0.9–30.5]). During the observation period β-IFN (70.4% of patients), glatiramer acetate (30.4%), natalizumab (16.8%), fingolimod (24.8%), dimethyl fumarate (24.0%), alemtuzumab (6.0%), and teriflunomide (4.8%) were administered as monotherapy. Change of pattern in step therapy was significantly different in cancer patients vs unaffected individuals (p = 0.011) (29.4% did not receive DMTs [p = 0.000]). Extended Cox model: Smoking (HR = 3.938, CI 95% 1.392–11.140, p = 0.010), being female (HR = 2.006, 1.070–3.760, p = 0.030), and age at MS diagnosis (AGE-DG) (HR = 1.036, 1.012–1.061, p = 0.004) were risk factors for neoplasm development. Secondary progressive MS (SPMS) phenotype (HR = 0.179, 0.042–0.764, p = 0.020) and treatment-time with IFN (HR = 0.923, 0.873–0.977, p = 0.006) or DMF (HR = 0.725, 0.507–1.036, p = 0.077) were protective factors. Tobacco and IFN lost their negative/positive influence as survival time increased. Cox PH model: Tobacco/AGE-DG interaction was a risk factor for cancer (HR = 1.099, 1.001–1.208, p = 0.049), followed by FLM treatment-time (HR = 1.219, 0.979–1.517). In conclusion, smoking, female sex, and AGE-DG were risk factors, and SPMS and IFN treatment-time were protective factors for neoplasm development; smoking/AGE-DG interaction was the main cancer risk factor.

Cancer and multiple sclerosis: 2023 recommendations from the French Multiple Sclerosis Society

“…The duration of exposure to dimethyl fumarate was found to be protective, with a hazard ratio of 0.725 (95% confidence interval (CI) = 0.507–1.036, p = 0.077), indicating a reduction in cancer risk of 27% for each year of treatment. 55 In contrast, a study using data from the worldwide Vigibase between 1 January 2000 and 9 January 2019 demonstrated a significant association between dimethyl fumarate and the reporting of cancer in the univariate analysis. The association was more pronounced in females (76.9%) and predominantly observed in individuals aged between 45 and 64 years (58.4%), with a median time to onset of 13 months.…”

Clinical use of dimethyl fumarate in multiple sclerosis treatment: an update to include China, using a modified Delphi method

“… 117 Overall, the malignancy rate in patients treated with DMF is similar to age- and sex-matched individuals without MS. 118 Duration of DMF treatment was concluded as a risk protective factor against neoplasms, in a small Spanish study. 119 Recent database analyses have produced conflicting results, with one finding no evidence of an increased cancer risk 120 and the other being the first publication to find an increased risk of neoplasm with DMF. 121 Consequently, it may be prudent to be vigilant in checking for cancer in DMF-treated patients, but this does not yet support a malignancy rate higher than the general population.…”

Is cancer risk reduced in multiple sclerosis? Results from a tertiary referral center

“…However, studies regarding the effect of DMTs on cancer have obtained contradictory results, with some resulting in an increased risk of cancer, while others have shown no increased cancer risk. This disparity is further complicated by the various types of DMTs used in patients with MS [ 20 , 28 – 31 ]. A Danish nationwide cohort study also found that DMTs in Danish MS patients were neither accompanied by an increase in cancer incidence nor an increase in cancer-specific mortality [ 18 ].…”