Eurology 68: A364. Kieseier BC, Archelos JJ, Hartung HP Different effects of simvastatin and interferon beta on the proteolytic activity of matrix metalloproteinases. Arch Neurol 61: 929932. Feng X, Han D, Kilaru BK, Franek BS, Niewold TB, et al. Inhibition of interferon-beta responses in multiple sclerosis immune cells associated with highdose statins. Arch Neurol 69: 13031309. Vollmer T, Key L, Durkalski V, Tyor W, Corboy J, et al. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 363: 16071608. Chataway J The MS-STAT trial: high dose simvastatin demonstrates neuroprotection without immune-modulation in secondary progressive muliple sclerosis a phase II trial. Oral presentation. ECTRIMS. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 10 ~~ ~~ Ulcerative colitis is a chronic disease characterized by diffuse mucosal inflammation within the colon, often with alternating periods of exacerbation and remission. This disease has conventionally been treated with 5-aminosalicylic acid, corticosteroids and oral immunosuppressant with the goals of achieving clinical or mucosal remission, and/or eliminating long-term corticosteroid use. However, these AKT inhibitor 2 biological activity conventional therapies are in many instances ineffective or cannot be tolerated by the patients. This failure to pervasively treat UC patients is apparent in the frequency of colectomies performed; the cumulative probability of colectomy from the time of diagnosis is 13.1% at 5 years, 18.9% at 10 years, and 25.4% at 20 years. This deficit in widespread, effective treatment of UC patients therefore warrants the development and study of alternative treatments. One potential alternative therapy is inhibition of tumor necrosis factor alpha as previous studies have established a correlation between increased production of TNF-a and UC pathophysiology. 1 Meta-Analysis: Anti-TNF-a Agents for Refractory UC Currently, the anti-TNF-a agents most commonly used for UC treatment are infliximab and adalimumab. Intravenous and subcutaneous administration of IFX and ADA, respectively, has been shown by some studies to be effective for treating moderately to severely active UC. However, other studies pertaining to IFX treatment have yielded conflicting results. Another anti-TNF-a agents, golimumab, induces and maintains clinical remission in patients with moderate to severe UC as evidenced by two recent trials. The need for alternative UC therapies, as well as the range and conflicting reports found from studies on anti-TNF-a therapeutics, encouraged us to perform a meta-analysis to analyze the efficacy of these agents for UC patients who were intolerant or refractory to conventional medical therapy. Several systematic reviews and meta-analyses of TNF-a blockers as treatment for UC have been published in recent years _ENREF_10. However, these failed to fully take into account heterogeneity between the trials analyzed, including 12926553 differences in the severity of UC in patients studied, drugs administered within the control group, and the point at which patient follow-up concluded. Moreover, the doses of the anti-TNF-a agent varied between different studies that had been included. As expected, these discrepancies HIV-RT inhibitor 1 custom synthesis skewed the results of the previous meta-analyses. Because of this need to account for inconsistencies within previous analyses, as well as include recent findings concerning anti-TNF-a treatment, we conducted a meta-analysis of TNF-a blockers as therapy for.Eurology 68: A364. Kieseier BC, Archelos JJ, Hartung HP Different effects of simvastatin and interferon beta on the proteolytic activity of matrix metalloproteinases. Arch Neurol 61: 929932. Feng X, Han D, Kilaru BK, Franek BS, Niewold TB, et al. Inhibition of interferon-beta responses in multiple sclerosis immune cells associated with highdose statins. Arch Neurol 69: 13031309. Vollmer T, Key L, Durkalski V, Tyor W, Corboy J, et al. Oral simvastatin treatment in relapsing-remitting multiple sclerosis. Lancet 363: 16071608. Chataway J The MS-STAT trial: high dose simvastatin demonstrates neuroprotection without immune-modulation in secondary progressive muliple sclerosis a phase II trial. Oral presentation. ECTRIMS. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 10 ~~ ~~ Ulcerative colitis is a chronic disease characterized by diffuse mucosal inflammation within the colon, often with alternating periods of exacerbation and remission. This disease has conventionally been treated with 5-aminosalicylic acid, corticosteroids and oral immunosuppressant with the goals of achieving clinical or mucosal remission, and/or eliminating long-term corticosteroid use. However, these conventional therapies are in many instances ineffective or cannot be tolerated by the patients. This failure to pervasively treat UC patients is apparent in the frequency of colectomies performed; the cumulative probability of colectomy from the time of diagnosis is 13.1% at 5 years, 18.9% at 10 years, and 25.4% at 20 years. This deficit in widespread, effective treatment of UC patients therefore warrants the development and study of alternative treatments. One potential alternative therapy is inhibition of tumor necrosis factor alpha as previous studies have established a correlation between increased production of TNF-a and UC pathophysiology. 1 Meta-Analysis: Anti-TNF-a Agents for Refractory UC Currently, the anti-TNF-a agents most commonly used for UC treatment are infliximab and adalimumab. Intravenous and subcutaneous administration of IFX and ADA, respectively, has been shown by some studies to be effective for treating moderately to severely active UC. However, other studies pertaining to IFX treatment have yielded conflicting results. Another anti-TNF-a agents, golimumab, induces and maintains clinical remission in patients with moderate to severe UC as evidenced by two recent trials. The need for alternative UC therapies, as well as the range and conflicting reports found from studies on anti-TNF-a therapeutics, encouraged us to perform a meta-analysis to analyze the efficacy of these agents for UC patients who were intolerant or refractory to conventional medical therapy. Several systematic reviews and meta-analyses of TNF-a blockers as treatment for UC have been published in recent years _ENREF_10. However, these failed to fully take into account heterogeneity between the trials analyzed, including 12926553 differences in the severity of UC in patients studied, drugs administered within the control group, and the point at which patient follow-up concluded. Moreover, the doses of the anti-TNF-a agent varied between different studies that had been included. As expected, these discrepancies skewed the results of the previous meta-analyses. Because of this need to account for inconsistencies within previous analyses, as well as include recent findings concerning anti-TNF-a treatment, we conducted a meta-analysis of TNF-a blockers as therapy for.
