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Life without COX 2 inhibitors

BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7553.1287 (Published 01 June 2006) Cite this as: BMJ 2006;332:1287

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Life after coxibs – is chaos still ruling?

EDITOR—In their editorial “Life after coxibs” Shaughnessy and Gordon
deliver a narrative clinical review of alternatives to coxibs in arthritis
and chronic pain management (1). We agree with the authors that little is
lost if coxibs disappear. However, narrative reviews have the inherent
methodological weakness that selection of therapies and recommendations
may be circumstantial, and this editorial about alternatives to coxibs is
no exception to the rule. The editorial lacks substantial information
about priority in based on effect sizes, time-effect profiles and power of
evidence behind each of the 13 recommended therapies. And it does not seem
to make a difference which therapy is chosen. In our opinion, it actually
makes a difference which one of these therapies is chosen, and some of the
authors´ recommendations do not seem justified by evidence.
In the editorial on-drug options, such as exercise and weight loss are
rightfully claimed to be efficacious, but we think that they should be
mentioned as firstline alternatives in knee osteoarthritis as adviced by
Felson & Hunter in a recent clinical BMJ-review (2).

The authors recommend combining non-selective cox inhibitors with
misoprostol and other recommendations include topical NSAIDs,
acetaminophen (paracetamol), opioids and glucosamine sulphate (GS). The
above pharmacotherapies in addition to steroid injections and chondrotin
are the seven most common pharmacotherapies in Europe (3), and they have
recently been systematically reviewed and subjected to meta-analysis (4).
Baseline pain levels, effect sizes, time-effect profiles and power of
evidence have been thoroughly analysed, and some of these results
contradict Shaughnessy & Gordon´s recommendations.

Both GS and chondroitin were found in this meta-analysis to exhibit
rather small effect sizes of questionable clinical relevance. The Cochrane
review cited by the editorial did not find unequivocal positive evidence
from GS in general, as 8 out of 15 trials were negative. The positive
results came from 7 trials funded by a specific GS manufacturer. The large
independently-funded GAITT trial published in February 2006 (5) did not
find significant pain-relieving effects from neither GS nor chondrotin.
Paracetamol recommendations are common in guidelines in spite of a very
poor effect size (4).

The authors also claim that S-adenosylmethionine (SAMe) reduces pain
in osteoarthritis, but their own review reference and another meta-
analysis (6) actually found no pain-relieving effect from SAMe over
placebo.

Some complementary therapies like therapeutic taping and braces are
also claimed to be effective, and acupuncture is suggested to give a small
pain-relieving effect, while the authors point out limited evidence in
favour of therapeutic touch (TT), and electrical stimulation.

There are several question-marks associated with the assessment of
non-drug therapies in the editorial. We have found 36 placebo-controlled
trials in knee osteoarthritis with eight physical therapies. So why are
the authors recommending non-drug interventions with only one or two
published trials? For instance, the evidence behind TT is a single Medline
-indexed randomized controlled trial with TT with 25 knee osteoarthritis
patients (7), and thus has not been subjected to assessment of
methodological quality.

Therapeutic taping was also recommended in the editorial. But it has
only been tested in a single positive monotherapy trial (8), and the
effect was lost when combined with other interventions in a later trial by
the same group (9).

Electrical stimulation is also given a limited recommendation by the
authors while citing a Cochrane review with 3 trials (10). This cited
reference is in fact a review of electromagnetic fields therapy in
osteoarthritis, and not electrical stimulation.

The authors also fail to mention non-drug interventions like TENS and
low level laser therapy which have been systematically reviewed by
Cochrane (11) (12) and others (13) finding clinically relevant pain-
relieving effects from samples of 8 and 6 trials respectively.

It is becoming increasingly difficult for a general practitioner to
navigate towards “best practice” in the plethora of effectiveness claims.
The unfortunate truth is that several drug interventions are largely
ineffective. This is highlighted by findings where 1 in 4 osteoarthritis
patients uses self-medication, 1 in 2 osteoarthritis patients uses two
drugs or more for their osteoarthritis pain (OA Nation survey UK,
Arthritis Care 2003). In addition, more than half of chronic pain patients
(where arthritis is the largest diagnostic group) do not feel that their
pain is adequately controlled by drugs (14).

Patients expect GPs and other clinicians to give meaningful advice
about medical as well as physical and complementary treatment. A
comprehensive systematic review comparing physical and complementary
therapies in OAK management is clearly needed. We agree that arthritis
management needs to be individually tailored, and in some cases therapies
which seem ineffective on a group level, could be of value to the
individual patient. But it would have been more helpful if this editorial
had offered evidence-based guidance for osteoarthritis management based on
group level efficacy. As it stands the editorial adds to the chaos of life
after coxibs by their (almost) “anything goes” advice.

References

1. Shaughnessy AF, Gordon AE. Life without COX 2 inhibitors. Bmj
2006;332(7553):1287-8.

2. Hunter DJ, Felson DT. Osteoarthritis. Bmj 2006;332(7542):639-42.

3. Mazieres B, Schmidely N, Hauselmann HJ, Martin-Mola E, Serni U,
Verbruggen AA, et al. Level of acceptability of EULAR recommendations for
the management of knee osteoarthritis by practitioners in different
European countries. Ann Rheum Dis 2005:ard.2003.009431.

4. Bjordal JM, Klovning A, Ljunggren AE, Slordal L. Short-term
efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain:
A meta-analysis of randomised placebo-controlled trials. Eur J Pain 2006.

5. Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, et
al. Glucosamine, chondroitin sulfate, and the two in combination for
painful knee osteoarthritis. N Engl J Med 2006;354(8):795-808.

6. Witte S, Lasek R, Victor N. [Meta-analysis of the efficacy of
adenosylmethionine and oxaceprol in the treatment of osteoarthritis].
Orthopade 2002;31(11):1058-65.

7. Gordon A, Merenstein JH, D'Amico F, Hudgens D. The effects of
therapeutic touch on patients with osteoarthritis of the knee. J Fam Pract
1998;47(4):271-7.

8. Hinman RS, Crossley KM, McConnell J, Bennell KL. Efficacy of knee
tape in the management of osteoarthritis of the knee: blinded randomised
controlled trial. Bmj 2003;327(7407):135.

9. Bennell KL, Hinman RS, Metcalf BR, Buchbinder R, McConnell J,
McColl G, et al. Efficacy of physiotherapy management of knee joint
osteoarthritis: a randomised, double blind, placebo controlled trial. Ann
Rheum Dis 2005;64(6):906-12.

10. Hulme J, Robinson V, DeBie R, Wells G, Judd M, Tugwell P.
Electromagnetic fields for the treatment of osteoarthritis. Cochrane
Database Syst Rev 2002(1):CD003523.

11. Osiri M, Welch VV, Brosseau L, Shea B, McGowan J, Tugwell P, et
al. Transcutaneous electrical nerve stimulation for knee osteoarthritis
(Cochrane Review). Cochrane Database Syst Rev 2000;4.

12. Brosseau L, Robinson V, Wells G, Debie R, Gam A, Harman K, et al.
Low level laser therapy (Classes I, II and III) for treating rheumatoid
arthritis. Cochrane Database Syst Rev 2005(4):CD002049.

13. Bjordal JM, Lopes-Martins RAB, Klovning A. Is Quality Control of
Cochrane Reviews in Controversial Areas Sufficient? Journal of Alternative
and Complementary Medicine 2006;12(2):181-183.

14. Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey
of chronic pain in Europe: prevalence, impact on daily life, and
treatment. Eur J Pain 2006;10(4):287-333.

Competing interests:
None declared

Competing interests: No competing interests

14 June 2006
Jan M Bjordal
Postdoctoral Research Fellow
Jan H. Demmink, Rodrigo A.B. Lopes-Martins
University of Bergen