hi guys, I've been doing a tonne of research lately, and could post numerous articles but I will post perhaps one of the most thorough, it is 8 pages long but I do recommend everyone on here to read it! -http://www.medscape.com/viewarticle/752223_4 - is the link. but I have copy n pasted what I find extremely interesting, and this is factual of the efficacy of anti-map treatment when compared to perhaps what the majority of GI's believe to be the most effective anti-tnf therapy - infliximab.
"Of the previously summarized studies, perhaps the most well-known and widely criticized study of anti-MAP therapy (AMAT) in CD was that conducted by Selby et al. [54] Touted as a 'landmark study',[56] the controversial trial used anti-mycobacterial drugs against atypical mycobacteria (rifabutin, clarithromycin, clofazimine) with prednisolone to induce remission followed by maintenance therapy with AMAT (n = 102). At 16 weeks, an unprecedented 66% of patients (n = 102) on AMAT were in remission without further benefit beyond this point by per-protocol analysis. However as surmised by Feller et al. the results of the Australian trial "were not based on an intention-to-treat analysis and may have underestimated the beneficial effects of the drug".[13] By an intention-to-treat (ITT) analysis the remission rate was significantly higher in the AMAT group compared with placebo (Table 2) with a p-value of <0.005 at 52 weeks and <0.008 at 104 weeks. As expected, after cessation of medication at 102 weeks the difference between treatment and placebo at 156 weeks was not significant (p = 0.19). Had the trial been based on an ITT analysis, as is the case with a number of other CD drugs on the market, the remission rate for AMAT would probably have been much higher.[13,55] The drop in efficacy over time is uncharacteristic compared with previous studies and may be attributed to two problems identified in the trial. First, the authors used "a suboptimal dose of clofazamine (50 mg/day) and other antibiotics",[57] and second, by the author's own admission, the clofazamine capsule "failed to rupture due to hardening of the outer gelatine capsule shell, resulting in a period of approximately 10 months where patients were likely not exposed to the correct dosage of clofazamine";[54] however, these patients were not replaced. Taken together, the results of the Selby trial were surprisingly good in spite of the shortcomings of the Australian Phase III trial. To demonstrate the superior efficacy of the treatment in CD it is essential to compare the results of the Selby trial with those of other CD treatments currently on the market, such as the anti-TNF therapy infliximab. AMAT remains a far more effective treatment than published results for infliximab, which reported remission rates of 39% at 12 weeks in the ACCENT I trial.[58,59] For example, on an ITT analysis, the AMAT remission rate at 16 weeks was 66% compared with 39% at 12 week for infliximab. Although no data is available for the trial of infliximab at 52 weeks, the ITT AMAT remission rate at 52 weeks was 41% compared with 26% at 26 weeks for the highest dose of infliximab used. The AMAT remission rate was also higher than that achieved with the recently US FDA-approved humanized anti-TNF antibody (adalimumab) in the CHARM trial, with the ITT remission rate of 24% for adalimumab at 52 weeks calculated for the highest dose.[60] The demonstrated superior results of anti-MAP therapy over other treatments currently on the market for CD support their use as a preferred primary treatment. This view was echoed by Feller et al. in their recent meta-analysis of antibiotic therapy in CD, who reported on the "potentially more favorable adverse effect profile and lower costs" of antibiotic therapy compared with infliximab.[13] With the serious, and at times fatal side effects encountered with anti-TNF therapy,[61,62] coupled with an efficacy below 39%,[57] it could readily be argued that failure to inform patients of this safe and effective antibiotic CD treatment may expose physicians to the question of 'duty of care' with its legal implications."
"Of the previously summarized studies, perhaps the most well-known and widely criticized study of anti-MAP therapy (AMAT) in CD was that conducted by Selby et al. [54] Touted as a 'landmark study',[56] the controversial trial used anti-mycobacterial drugs against atypical mycobacteria (rifabutin, clarithromycin, clofazimine) with prednisolone to induce remission followed by maintenance therapy with AMAT (n = 102). At 16 weeks, an unprecedented 66% of patients (n = 102) on AMAT were in remission without further benefit beyond this point by per-protocol analysis. However as surmised by Feller et al. the results of the Australian trial "were not based on an intention-to-treat analysis and may have underestimated the beneficial effects of the drug".[13] By an intention-to-treat (ITT) analysis the remission rate was significantly higher in the AMAT group compared with placebo (Table 2) with a p-value of <0.005 at 52 weeks and <0.008 at 104 weeks. As expected, after cessation of medication at 102 weeks the difference between treatment and placebo at 156 weeks was not significant (p = 0.19). Had the trial been based on an ITT analysis, as is the case with a number of other CD drugs on the market, the remission rate for AMAT would probably have been much higher.[13,55] The drop in efficacy over time is uncharacteristic compared with previous studies and may be attributed to two problems identified in the trial. First, the authors used "a suboptimal dose of clofazamine (50 mg/day) and other antibiotics",[57] and second, by the author's own admission, the clofazamine capsule "failed to rupture due to hardening of the outer gelatine capsule shell, resulting in a period of approximately 10 months where patients were likely not exposed to the correct dosage of clofazamine";[54] however, these patients were not replaced. Taken together, the results of the Selby trial were surprisingly good in spite of the shortcomings of the Australian Phase III trial. To demonstrate the superior efficacy of the treatment in CD it is essential to compare the results of the Selby trial with those of other CD treatments currently on the market, such as the anti-TNF therapy infliximab. AMAT remains a far more effective treatment than published results for infliximab, which reported remission rates of 39% at 12 weeks in the ACCENT I trial.[58,59] For example, on an ITT analysis, the AMAT remission rate at 16 weeks was 66% compared with 39% at 12 week for infliximab. Although no data is available for the trial of infliximab at 52 weeks, the ITT AMAT remission rate at 52 weeks was 41% compared with 26% at 26 weeks for the highest dose of infliximab used. The AMAT remission rate was also higher than that achieved with the recently US FDA-approved humanized anti-TNF antibody (adalimumab) in the CHARM trial, with the ITT remission rate of 24% for adalimumab at 52 weeks calculated for the highest dose.[60] The demonstrated superior results of anti-MAP therapy over other treatments currently on the market for CD support their use as a preferred primary treatment. This view was echoed by Feller et al. in their recent meta-analysis of antibiotic therapy in CD, who reported on the "potentially more favorable adverse effect profile and lower costs" of antibiotic therapy compared with infliximab.[13] With the serious, and at times fatal side effects encountered with anti-TNF therapy,[61,62] coupled with an efficacy below 39%,[57] it could readily be argued that failure to inform patients of this safe and effective antibiotic CD treatment may expose physicians to the question of 'duty of care' with its legal implications."
