RESEARCH - Azithromycin fails in reactive arthritis

[Guest guest]

Azithromycin fails in reactive arthritis

Rheumawire

September 17, 2004

Janis

Oslo, Norway - Extended treatment with azithromycin had little effect on

reactive arthritis in a double-blind, placebo-controlled study reported

by Dr Tore K Kvien (Diakkonhjemmet Hospital, Oslo, Norway) and

colleagues in the September 2004 issue of the ls of the Rheumatic

Diseases [1]. Kvien, reporting for 11 investigators in the

multi-institution European Union League Against Rheumatism (EULAR)

clinical trial, concluded, " This large trial has demonstrated that

prolonged treatment with azithromycin is ineffective. "

" The implication is that long-term treatment with antibiotics is not

justified when treating suspected reactive arthritis, " Kvien tells

rheumawire. " The only possible exception could be verified

chlamydia-induced arthritis, because some previous controlled clinical

trials have indicated a benefit from prolonged (12-week) treatment with

tetracyclines. "

" I have read with interest the results of the international trial of

azithromycin in reactive arthritis. The results are really identical

with those of our own study [2] and of Sieper et al [3]. That is, after

reactive arthritis has develops, neither short-term nor long-term

antibiotic treatment appears to have any effect on the course as

followed for 1 year, " reactive-arthritis expert Dr Auli Toivanen (Turku

University, Satalinna Hospital, Finland) tells rheumawire. Toivanen, who

was not involved in the EULAR study, adds, " If antibiotics are given

before the pathogenetic process has well started, they may be useful. "

The EULAR researchers set out to determine the effect of weekly oral

azithromycin given for 13 weeks on the severity and resolution of

reactive arthritis. They enrolled 186 patients from 12 countries in a

randomized, double-blind, placebo-controlled trial. Eligibility criteria

included inflammatory arthritis with 6 or more swollen joints and

disease duration less than 6 months. A single dose of azithromycin was

given to all patients as conventional treatment for possible Chlamydia

infection, and then patients were randomized to weekly azithromycin

(n=81) or to weekly placebo (n=71) for 12 weeks.

Patients were assessed every 4 weeks for 24 weeks. The primary efficacy

measures were physician assessment of disease activity, patient

assessment of disease activity, number of swollen joints, number of

tender joints, and time to resolution of arthritis (absence of joint

swelling and pain).

Azithromycin was not significantly better than placebo on any of the

study end points using intention-to-treat analysis or using just those

patients who completed the entire study. Patients in the azithromycin

group did report more adverse effects, mainly gastrointestinal

(p=0.006).

" In summary, this study does not support the use of a prolonged course

of antibiotics for the alleviation of reactive arthritis. This is an

important conclusion, because such treatment has become commonplace,

perhaps as a reasonable response to the demonstration of organisms in

the reactive arthritis joint. Instead, disease-modifying drugs such as

sulfasalazine and possibly methotrexate may be justified in severe

disease that fails to resolve spontaneously, and there are now also

reports of efficacy of tumor-necrosis-factor-blocking compounds in

chronic reactive arthritis, " Kvien et al concluded.

" Several possible questions can be raised related to the

pathophysiology, " Kvien tells rheumawire. " It can be argued that

persistent infection is not relevant to pathogenesis and that infection

can be a trigger of some form of autoimmune disease, directed against,

for example, joint components. Another possible interpretation could be

that persistent infection plays a crucial part in the pathogenesis, but

that the organisms triggering reactive arthritis enter a state with low

susceptibility to antibiotics. "

Toivanen says that at present, the treatment of reactive arthritis is

still based on rest, anti-inflammatory nonsteroidal drugs, or

corticosteroids either intra-articularly or systemically. " There are no

really good studies on the effect of the new biological agents in

reactive arthritis, but they have been used in some cases. I myself

could consider them in severe cases in which a response to

corticosteroids would not be good, " Toivanen says.

Sources

Kvien TK, Gaston JSH, Bardin T, et al. Three-month

treatment of reactive arthritis with azithromycin: a EULAR double blind,

placebo controlled study. Ann Rheum Dis 2004; 63:1113-1119.

Yli-Kerttula T, Luukkainen R, Yli-Kerttula U, et al.

Effect of a three month course of ciprofloxacin on the outcome of

reactive arthritis. Ann Rheum Dis 2000; 59:565-70.

Sieper J, Fendler C, Laitko S, et al. No benefit of

long-term ciprofloxacin treatment in patients with reactive arthritis

and undifferentiated oligoarthritis: a three-month multicenter,

double-blind, randomized, placebo-controlled study. Arthritis Rheum

1999; 42:1386-96.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org