Fluoroquinolones and risk of Achilles tendon disorders: case-control study
BMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7349.1306 (Published 01 June 2002) Cite this as: BMJ 2002;324:1306
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In assessing the relationship between fluoroquinolones and tendon
disorders, van der Linden et al conclude that 'The effect seems to be
restricted to people aged 60 or over'. I am not convinced. We are not told
the rationale for comparing a subgroup of elderly patients with younger
patients: was it a prespecified hypothesis that old and young patients
would be different, or was this subgroup analysis done after the authors
had already noticed a difference between elderly and young patients in
their dataset? Why was the cutoff of 60 years chosen? Because of a
prespecified hypothesis, or because this was the cutoff that made the
difference between elderly and young patients look most impressive?
It is almost always possible to find a difference between subgroups
if you look at enough subgroups, especially if you are prepared to
dichotomise in a post-hoc manner. The finding of a difference between
elderly and young patients in this dataset is not compelling evidence of a
genuine age difference, if the presentation of results was driven by the
data.
Furthermore, van der Linden et al do not present the results of an
interaction test between fluoroquinolone use and age, so we have not been
told the magnitude of the age difference or its confidence interval.
Competing interests: No competing interests
The study by Van der Linden et al. raises several questions. First,
in the publication it was mentioned, that the base cohort was defined by
subjects aged older than 18 years who had received a fluoroquinolone
(46776 subjects). Cases and Controls were identified out of this base
cohort. Further in both groups four categories of exposure were defined.
But one category is labelled as “no use”, which contradicts the defined
characteristics of the base cohort. Therefore the origin of the “no use”
subjects in the cases as well in the controls is obscure (see table). As
the “no use” subjects serve as reference to calculate the relative risks,
the origin of this group should have been stated clearly. Since the aim of
the study was to identify an association of fluorochinolones with Achilles
tendon disorders, it does not make sense to include only subjects who have
this risk factor anyway. Therefore it is not obvious which criteria were
applied to include subjects in the study cohort beside the use of
fluorochinolones.
Second, we missed diagnostic criteria to differentiate between the
Achilles tendon disorders. From a practical point of view we see no reason
why to make a distinction between Achilles tendon disorders and
tendinitis.
Third, we missed a description of how cases were identified in a
database containing 1-2 million inhabitants.
Kind regards
Michael Koller 1
Milo Puhan 1
1 Horten-Zentrum für praxisorientierte Forschung und Wissenstransfer
Universitätsspital Zürich
Bolleystrasse 40
8091 Zürich
Switzerland
Competing interests: No competing interests
The quinolone related tendinopathy is an uncommon side effect of this
family of drugs, that generally implies the withdrawal of the quinolone
and not giving any other drug of this kind because it high frequency of
class effect of this collateral effect. Although the most common place of
presentation is the Aquilles tendon, it may be located in other places
(1). In this basis, the incidence of the total percentage of the quinolone
tendinopathies may be higher than the regitered in the study. By the other
way, it would be of great interest knowing if any kind of quinolone was
specially related to the incidence of tendinopathy because in a recent
study carried out, Ofloxacin was found to be the most common quinolone
associated with tendinopathy(2) and was also related to the most severe
presentation of the condition. Although the physiopathology of the side
effect is not known, it seems to be an inflammatory response. In that
basis, we treated a patient with colchicine in a n=1 randomized controlled
trial with successs (3). Finally, we would like to add that despite the
class effect of this drugs, the new quinolones, like Levofloxacin and
Moxifloxacin, seems not to have this characteristic (3), that would allow
the clinician giving this kind of drugs if necessary.
References
1.Casparian JM, Luchi M, Moffat RE, Hinthorn D. Quinolones and tendon
ruptures. South Med J 2000;93:488-491.
2.Van der Linden PD, Van de Lei J, Nab HW, Knol A, Striker BH. Achilles
tendinitis associated with fluorquinolones. Br J Pharmacol 1999;48:433-7.
3. Rodriguez-Vera FJ,Pereira Vega A, Pujol de la Llave E. Tendinopathy by
quinolones: treatment and class effect in two new cases. Rev Clin Esp (in
press)
Competing interests: No competing interests
fluoroquinolones for runners?
Are very active people (for instance marathon runners) more likely to
suffer fluoroquinolone-related tendon problems? It seems obvious that
caution should be used in prescribing, but have any studies shown that
athletes are more likely to be affected?
Competing interests:
None declared
Competing interests: No competing interests