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6 results on '"Sirbu C."'

1. Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years

Author

Kalincik, T, Diouf, I, Sharmin, S, Malpas, C, Spelman, T, Horakova, D, Havrdova, EK, Trojano, M, Izquierdo, G, Lugaresi, A, Prat, A, Girard, M, Duquette, P, Grammond, P, Jokubaitis, V, Van der Walt, A, Grand'Maison, F, Sola, P, Ferraro, D, Shaygannejad, V, Alroughani, R, Hupperts, R, Terzi, M, Boz, C, Lechner-Scott, J, Pucci, E, Van Pesch, V, Granella, F, Bergamaschi, R, Spitaleri, D, Slee, M, Vucic, S, Ampapa, R, McCombe, P, Ramo-Tello, C, Prevost, J, Olascoaga, J, Cristiano, E, Barnett, M, Saladino, ML, Sanchez-Menoyo, JL, Hodgkinson, S, Rozsa, C, Hughes, S, Moore, F, Shaw, C, Butler, E, Skibina, O, Gray, O, Kermode, A, Csepany, T, Singhal, B, Shuey, N, Piroska, I, Taylor, B, Simo, M, Sirbu, C-A, Sas, A, Butzkueven, H, Kalincik, T, Diouf, I, Sharmin, S, Malpas, C, Spelman, T, Horakova, D, Havrdova, EK, Trojano, M, Izquierdo, G, Lugaresi, A, Prat, A, Girard, M, Duquette, P, Grammond, P, Jokubaitis, V, Van der Walt, A, Grand'Maison, F, Sola, P, Ferraro, D, Shaygannejad, V, Alroughani, R, Hupperts, R, Terzi, M, Boz, C, Lechner-Scott, J, Pucci, E, Van Pesch, V, Granella, F, Bergamaschi, R, Spitaleri, D, Slee, M, Vucic, S, Ampapa, R, McCombe, P, Ramo-Tello, C, Prevost, J, Olascoaga, J, Cristiano, E, Barnett, M, Saladino, ML, Sanchez-Menoyo, JL, Hodgkinson, S, Rozsa, C, Hughes, S, Moore, F, Shaw, C, Butler, E, Skibina, O, Gray, O, Kermode, A, Csepany, T, Singhal, B, Shuey, N, Piroska, I, Taylor, B, Simo, M, Sirbu, C-A, Sas, A, and Butzkueven, H

Abstract

OBJECTIVE: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients. METHODS: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity. RESULTS: A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, p = 0.0016), worsening of disability (0.56, 0.38-0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, p = 10-9) and worsening of disability (0.81, 0.67-0.99, p = 0.043). CONCLUSION: Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.

Published
2021

2. Effect of disease modifying therapy on disability in Relapsing-Remitting multiple sclerosis over 15 Years

Author

Kalincik, T., Diouf, I., Sharmin, S., Malpas, C., Spelman, T., Horakova, D., Havrdova, E.K., Trojano, M., Izquierdo, G., Lugaresi, A., Prat, A., Girard, M., Duquette, P., Grammond, P., Jokubaitis, V., Van der Walt, A., Grand'Maison, F., Sola, P., Ferraro, D., Shaygannejad, V., Alroughani, R., Hupperts, R., Terzi, M., Boz, C., Lechner-Scott, J., Pucci, E., van Pesch, V., Granella, F., Bergamaschi, R., Spitaleri, D., Slee, M., Vucic, S., Ampapa, R., McCombe, P., Ramo-Tello, C., Prevost, J., Olascoaga, J., Cristiano, E., Barnett, M., Saladino, M.L., Sanchez-Menoyo, J.L., Hodgkinson, S., Rózsa, C., Hughes, S., Moore, F., Shaw, C., Butler, E., Skibina, O., Gray, O., Kermode, A., Csepany, T., Singhal, B., Shuey, N., Piroska, I., Taylor, B., Simon, M., Sirbu, C-A, Sas, A., Butzkueven, H., Kalincik, T., Diouf, I., Sharmin, S., Malpas, C., Spelman, T., Horakova, D., Havrdova, E.K., Trojano, M., Izquierdo, G., Lugaresi, A., Prat, A., Girard, M., Duquette, P., Grammond, P., Jokubaitis, V., Van der Walt, A., Grand'Maison, F., Sola, P., Ferraro, D., Shaygannejad, V., Alroughani, R., Hupperts, R., Terzi, M., Boz, C., Lechner-Scott, J., Pucci, E., van Pesch, V., Granella, F., Bergamaschi, R., Spitaleri, D., Slee, M., Vucic, S., Ampapa, R., McCombe, P., Ramo-Tello, C., Prevost, J., Olascoaga, J., Cristiano, E., Barnett, M., Saladino, M.L., Sanchez-Menoyo, J.L., Hodgkinson, S., Rózsa, C., Hughes, S., Moore, F., Shaw, C., Butler, E., Skibina, O., Gray, O., Kermode, A., Csepany, T., Singhal, B., Shuey, N., Piroska, I., Taylor, B., Simon, M., Sirbu, C-A, Sas, A., and Butzkueven, H.

Abstract

Objective To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients. Methods We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity. Results A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43–0.82, p = 0.0016), worsening of disability (0.56, 0.38–0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19–0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50–0.70, p = 10−9) and worsening of disability (0.81, 0.67–0.99, p = 0.043). Conclusion Continued treatment with MS immunotherapies reduces disability accrual by 19%–44% (95% CI 1%–62%), the risk of need of a walking aid by 67% (95% CI 41%–81%), and the frequency of relapses by 40–41% (95% CI 18%–57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term. Classification of Evidence This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.

Published
2020

6. Combination Drug Therapy of Pioglitazone and D-cycloserine Attenuates Chronic Orofacial Neuropathic Pain and Anxiety by Improving Mitochondrial Function Following Trigeminal Nerve Injury.

Author

Lyons DN, Zhang L, Pandya JD, Danaher RJ, Ma F, Miller CS, Sullivan PG, Sirbu C, and Westlund KN

Subjects
Animals, Anti-Anxiety Agents pharmacology, Anxiety drug therapy, Anxiety metabolism, Brain drug effects, Brain metabolism, Chronic Pain metabolism, Chronic Pain psychology, Cognition drug effects, Disease Models, Animal, Drug Therapy, Combination, Facial Pain metabolism, Facial Pain psychology, Hyperalgesia drug therapy, Hyperalgesia metabolism, Hyperalgesia psychology, Male, Mice, Inbred C57BL, Mitochondria drug effects, Mitochondria metabolism, Neuralgia metabolism, Neuralgia psychology, Random Allocation, Trigeminal Nerve Injuries metabolism, Trigeminal Nerve Injuries psychology, Analgesics pharmacology, Chronic Pain drug therapy, Cycloserine pharmacology, Facial Pain drug therapy, Neuralgia drug therapy, Pioglitazone pharmacology, Trigeminal Nerve Injuries drug therapy
Abstract

Objectives: The study aim was to determine how peripheral trigeminal nerve injury affects mitochondrial respiration and to test efficacy of combined treatment with 2 Federal Drug Administration approved drugs with potential for improving mitochondrial bioenergetics, pain and anxiety-related behaviors in a chronic orofacial neuropathic pain mouse model., Methods: Efficacy of (R)-(+)-4-amino-3-isoxazolidinone (D-cycloserine, DCS), an N-Methyl-D-aspartate antagonist/agonist, and Pioglitazone (PIO), a selective agonist of nuclear receptor peroxisome proliferator-activated receptor gamma was investigate in the trigeminal inflammatory compression (TIC) neuropathic nerve injury mouse model. Combined low doses of these drugs (80 mg/kg DCS and 100 mg/kg PIO) were given as a single bolus or daily for 7 days post-TIC to test ability to attenuate neuropathic nociceptive and associated cognitive dependent anxiety behaviors. In addition, beneficial effects of the DCS/PIO drug combination were explored ex vivo in isolated cortex/brainstem mitochondria at 28 weeks post-TIC., Results: The DCS/PIO combination not only attenuated orofacial neuropathic pain and anxiety-related behaviors associated with trigeminal nerve injury, but it also improved mitochondrial bioenergetics., Discussion: The DCS/PIO combination uncoupled mitochondrial respiration in the TIC model to improve cortical mitochondrial dysfunction, as well as reduced nociceptive and anxiety behaviors present in mice with centralized chronic neuropathic nerve injury. Combining these drugs could be a beneficial treatment for patients with depression, anxiety, or other psychological conditions due to their chronic pain status.

Published
2018
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