Gibson's phase III Crohn's trial published

[Guest guest]

" Using combination antibiotic therapy with clarithromycin, rifabutin,

and clofazimine for up to 2 years, we did not find evidence of a

sustained benefit. "

I don't have the full text.

Bummer...

They say abx were used " for up to 2 years, " so I am not so interested

in the outcome at 36 months. It's the non-significance of the benefit

at 24 months that's really disappointing.

======================================

Gastroenterology. 2007 Jun;132(7):2313-2319. Epub 2007 Mar 21.

Two-Year Combination Antibiotic Therapy With Clarithromycin,

Rifabutin, and Clofazimine for Crohn's Disease.

Selby W, Pavli P, Crotty B, Florin T, Radford- G, Gibson P,

B, Connell W, Read R, Merrett M, Ee H, Hetzel D; Antibiotics

in Crohn's Disease Study Group.

Royal Prince Alfred Hospital, Sydney, Australia.

Background & Aims: Mycobacterium avium subspecies paratuberculosis

has been proposed as a cause of Crohn's disease\. We report a

prospective, parallel, placebo-controlled, double-blind, randomized

trial of 2 years of clarithromycin, rifabutin, and clofazimine in

active Crohn's disease, with a further year of follow-up\. Methods:

Two hundred thirteen patients were randomized to clarithromycin 750

mg/day, rifabutin 450 mg/day, clofazimine 50 mg/day or placebo, in

addition to a 16-week tapering course of prednisolone\. Those in

remission (Crohn's Disease Activity Index </=150) at week 16 continued

their study medications in the maintenance phase of the trial\.

Primary end points were the proportion of patients experiencing at

least 1 relapse at 12, 24, and 36 months\. Results: At week 16, there

were significantly more subjects in remission in the antibiotic arm

(66%) than the placebo arm (50%; P = .02)\. Of 122 subjects entering

the maintenance phase, 39% taking antibiotics experienced at least 1

relapse between weeks 16 and 52, compared with 56% taking placebo (P =

..054)\. At week 104, the figures were 26% and 43%, respectively (P =

..14)\. During the following year, 59% of the antibiotic group and 50%

of the placebo group relapsed (P = .54)\. Conclusions: Using

combination antibiotic therapy with clarithromycin, rifabutin, and

clofazimine for up to 2 years, we did not find evidence of a sustained

benefit\. This finding does not support a significant role for

Mycobacterium avium subspecies paratuberculosis in the pathogenesis of

Crohn's disease in the majority of patients\. Short-term improvement

was seen when this combination was added to corticosteroids, most

likely because of nonspecific antibacterial effects.

PMID: 17570206 [PubMed - as supplied by publisher]

[Guest guest]

Most of these drugs work only for a few days and the rest of the time

they are useless in my general dealings with them. You may get a good

week or two with clarithromycin, rifampicin turns on a dime.I don't

know about the third.I also don't feel that chasing a myco bacteria

species and avoiding the organisms found that may be putting out

harmfull substances- is the smart way of attacking this disease

process...

>

> " Using combination antibiotic therapy with clarithromycin,

rifabutin,

> and clofazimine for up to 2 years, we did not find evidence of a

> sustained benefit. "

>

> I don't have the full text.

>

> Bummer...

>

> They say abx were used " for up to 2 years, " so I am not so

interested

> in the outcome at 36 months. It's the non-significance of the

benefit

> at 24 months that's really disappointing.

>

>

> ======================================

>

>

>

>

> Gastroenterology. 2007 Jun;132(7):2313-2319. Epub 2007 Mar 21.

>

> Two-Year Combination Antibiotic Therapy With Clarithromycin,

> Rifabutin, and Clofazimine for Crohn's Disease.

>

> Selby W, Pavli P, Crotty B, Florin T, Radford- G, Gibson P,

> B, Connell W, Read R, Merrett M, Ee H, Hetzel D;

Antibiotics

> in Crohn's Disease Study Group.

>

> Royal Prince Alfred Hospital, Sydney, Australia.

>

> Background & Aims: Mycobacterium avium subspecies

paratuberculosis

> has been proposed as a cause of Crohn's disease\. We report a

> prospective, parallel, placebo-controlled, double-blind, randomized

> trial of 2 years of clarithromycin, rifabutin, and clofazimine in

> active Crohn's disease, with a further year of follow-up\. Methods:

> Two hundred thirteen patients were randomized to clarithromycin 750

> mg/day, rifabutin 450 mg/day, clofazimine 50 mg/day or placebo, in

> addition to a 16-week tapering course of prednisolone\. Those in

> remission (Crohn's Disease Activity Index </=150) at week 16

continued

> their study medications in the maintenance phase of the trial\.

> Primary end points were the proportion of patients experiencing at

> least 1 relapse at 12, 24, and 36 months\. Results: At week 16,

there

> were significantly more subjects in remission in the antibiotic arm

> (66%) than the placebo arm (50%; P = .02)\. Of 122 subjects entering

> the maintenance phase, 39% taking antibiotics experienced at least 1

> relapse between weeks 16 and 52, compared with 56% taking placebo

(P =

> .054)\. At week 104, the figures were 26% and 43%, respectively (P =

> .14)\. During the following year, 59% of the antibiotic group and

50%

> of the placebo group relapsed (P = .54)\. Conclusions: Using

> combination antibiotic therapy with clarithromycin, rifabutin, and

> clofazimine for up to 2 years, we did not find evidence of a

sustained

> benefit\. This finding does not support a significant role for

> Mycobacterium avium subspecies paratuberculosis in the pathogenesis

of

> Crohn's disease in the majority of patients\. Short-term improvement

> was seen when this combination was added to corticosteroids, most

> likely because of nonspecific antibacterial effects.

>

> PMID: 17570206 [PubMed - as supplied by publisher]

>

[Guest guest]

Yes But- there weren't any significant relapses untill they went to

maintenance doses...

So is this a case of how one interprets data? ALthough we don't have

all the data (I haven't read the full paper either- but with a sister

in law with Crohns (and her daughter also has it) I'm interested.

Barb

>

> " Using combination antibiotic therapy with clarithromycin,

rifabutin,

> and clofazimine for up to 2 years, we did not find evidence of a

> sustained benefit. "

>

> I don't have the full text.

>

> Bummer...

>

> They say abx were used " for up to 2 years, " so I am not so

interested

> in the outcome at 36 months. It's the non-significance of the

benefit

> at 24 months that's really disappointing.

>

>

> ======================================

>

>

>

>

> Gastroenterology. 2007 Jun;132(7):2313-2319. Epub 2007 Mar 21.

>

> Two-Year Combination Antibiotic Therapy With Clarithromycin,

> Rifabutin, and Clofazimine for Crohn's Disease.

>

> Selby W, Pavli P, Crotty B, Florin T, Radford- G, Gibson P,

> B, Connell W, Read R, Merrett M, Ee H, Hetzel D;

Antibiotics

> in Crohn's Disease Study Group.

>

> Royal Prince Alfred Hospital, Sydney, Australia.

>

> Background & Aims: Mycobacterium avium subspecies

paratuberculosis

> has been proposed as a cause of Crohn's disease\. We report a

> prospective, parallel, placebo-controlled, double-blind, randomized

> trial of 2 years of clarithromycin, rifabutin, and clofazimine in

> active Crohn's disease, with a further year of follow-up\. Methods:

> Two hundred thirteen patients were randomized to clarithromycin 750

> mg/day, rifabutin 450 mg/day, clofazimine 50 mg/day or placebo, in

> addition to a 16-week tapering course of prednisolone\. Those in

> remission (Crohn's Disease Activity Index </=150) at week 16

continued

> their study medications in the maintenance phase of the trial\.

> Primary end points were the proportion of patients experiencing at

> least 1 relapse at 12, 24, and 36 months\. Results: At week 16,

there

> were significantly more subjects in remission in the antibiotic arm

> (66%) than the placebo arm (50%; P = .02)\. Of 122 subjects entering

> the maintenance phase, 39% taking antibiotics experienced at least 1

> relapse between weeks 16 and 52, compared with 56% taking placebo

(P =

> .054)\. At week 104, the figures were 26% and 43%, respectively (P =

> .14)\. During the following year, 59% of the antibiotic group and

50%

> of the placebo group relapsed (P = .54)\. Conclusions: Using

> combination antibiotic therapy with clarithromycin, rifabutin, and

> clofazimine for up to 2 years, we did not find evidence of a

sustained

> benefit\. This finding does not support a significant role for

> Mycobacterium avium subspecies paratuberculosis in the pathogenesis

of

> Crohn's disease in the majority of patients\. Short-term improvement

> was seen when this combination was added to corticosteroids, most

> likely because of nonspecific antibacterial effects.

>

> PMID: 17570206 [PubMed - as supplied by publisher]

>

[Guest guest]

> Yes But- there weren't any significant relapses untill they went to

> maintenance doses...

I'm not sure whether the maintenance phase in fact involved what you

would think of as lower doses, ie maintenance doses. Actually it's a

possibility I didn't think of.

> So is this a case of how one interprets data? ALthough we don't have

> all the data (I haven't read the full paper either- but with a sister

> in law with Crohns (and her daughter also has it) I'm interested.

Well, maybe there could be some artifacts or such in the design. I was

thinking about that. Notice all the primary outcome measures were

taken after people were selected into the maintenance phase.

Therefore, those who responded initially to placebo + steroids could

be different on average (more tractable disease) than those who

responded initially to abx + steroids. That could make it harder to

show a benefit from the abx.

On the other hand, the abx group was selected for responders to abx,

so that should make it a lot easier to show benefit for abx.

The whole thing is a little weird. Usually the whole point of a

randomized trial (and the reason it is gold-standard) is that the

groups compared are identical. In this case they are probably not

identical. But my subjective impression is that the " net

artifactuality " here would probably make abx appear more beneficial,

not less.

[Guest guest]

> I'm not sure whether the maintenance phase in fact involved what you

> would think of as lower doses, ie maintenance doses.

What I meant was:

I'm not sure whether the maintenance phase in fact involved what you

would think of as maintenance doses, ie lower doses.

[Guest guest]

For me and my friends, "maintenance dosages" are most certainly not "lower". That's a sure fire remedy for increasing the infection and turning the antibiotic completely worthless. penny <usenethod@...> wrote: > Yes But- there weren't any significant relapses untill they went to > maintenance doses...I'm not sure whether the maintenance phase in fact involved what youwould think of as lower doses, ie maintenance doses. Actually it's

apossibility I didn't think of.> So is this a case of how one interprets data? ALthough we don't have > all the data (I haven't read the full paper either- but with a sister > in law with Crohns (and her daughter also has it) I'm interested.Well, maybe there could be some artifacts or such in the design. I wasthinking about that. Notice all the primary outcome measures weretaken after people were selected into the maintenance phase.Therefore, those who responded initially to placebo + steroids couldbe different on average (more tractable disease) than those whoresponded initially to abx + steroids. That could make it harder toshow a benefit from the abx.On the other hand, the abx group was selected for responders to abx,so that should make it a lot easier to show benefit for abx. The whole thing is a little weird. Usually the whole point of arandomized trial (and the reason it is

gold-standard) is that thegroups compared are identical. In this case they are probably notidentical. But my subjective impression is that the "netartifactuality" here would probably make abx appear more beneficial,not less.