What are the effects of adding azathioprine to corticosteroids in polymyositis?

Meneses, Cristina; Rada, Gabriel

doi:10.5867/medwave.2015.6179

Peer-reviewed general biomedical journal

Living FRIendly Summaries of the Body of Evidence using Epistemonikos (FRISBEE)

Medwave 2015 Jul;15(Suppl 1):e6179 doi: 10.5867/medwave.2015.6179

What are the effects of adding azathioprine to corticosteroids in polymyositis?

Cristina Meneses, Gabriel Rada

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Abstract

The treatment of polymyositis is based on corticosteroid therapy, with addition of azathioprine for non responsive cases or as an attempt to diminish corticosteroids requirements. However, there is no clear evidence of its benefit in controlling symptoms. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified only one systematic review including one pertinent randomized trial. We generated a summary of findings following the GRADE approach. We concluded there is uncertainty if azathioprine improves or not muscular strength in polymyositis because the certainty of the evidence is very low.

Problem

Corticosteroids constitute the standard treatment for dermatomyositis and polymyositis. Given their multiple short and long term side effects there is interest in other immunomodulators, such as azathioprine, especially for non-responsive cases or as an attempt to diminish corticosteroids requirements. However, there is no clear evidence of its benefit in controlling symptoms, and it also carry important side effects.

Methods

We used Epistemonikos database, which is maintained by screening more than 30 databases, to identify systematic reviews and their included primary studies. With this information we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

There is uncertainty if azathioprine improves or not muscular strength in polymyositis because the certainty of the evidence is very low.
As far as we know there are no ongoing trials evaluating this question

About the body of evidence for this question

What is the evidence. See evidence matrix in Epistemonikos later	We found one systematic review [1] including only one pertinent randomized controlled trial [2].
What types of patients were included	The study included adults with polymyositis diagnosed with Bohan and Peter criteria and positive muscle biopsy Patients with previous corticosteroid or immunosuppresive therapy were excluded.
What types of interventions were included	Azathioprine 2mg/kg qd plus prednisone 60 mg qd, compared with prednisone 60 mg qd.
What types of outcomes were measured	Improvement in muscular strength evaluated in each muscular group (score from 0= no deficit, to -140= maximum deficit), serum creatine kinase, muscular biopsy (0= normal, to 36= maximum inflammation).

Summary of findings

The information on the effects of azathioprine is based on one randomized controlled trial [2] including 16 patients.

There is uncertainty if azathioprine improves or not muscular strength in polymyositis. The certainty of the evidence is very low.

Other considerations for decision-making

To whom this evidence does and does not apply

The study included patients with polymyositis meeting Bohan and Peter criteria, so the evidence found is applied directly to this group. It is clinically reasonable to extend this findings to patients with dermatomyositis with muscular involvement.
It does not clearly apply to pediatric patients or patients with other rheumatologic diagnosis or presenting overlap syndrome.

About the outcomes included in this summary

The outcomes presented are those considered critical for decision-making, according to the authors of this summary. We did not find clinical guidelines or studies about the relative importance of the outcomes for this condition.

Balance between benefits and risks, and certainty of the evidence

It is not possible to estimate the risk/benefit given the existing uncertainty. Considering the intervention has side effects and costs its use outside of the context of a clinical trial is questionable.

What would patients and their doctors think about this intervention

Given the absence of a clearly established alternative treatment, it is possible some clinicians will consider using this drug, especially in refractory patients. Some patients putting more value on the hypothetical benefit than on the risks and costs, may be inclined to use it too. In these cases, it is extremely important to inform the patient about the certainty of the evidence.

Resource considerations

Given the uncertainty about the benefits, it is not possible to make a judgment about the cost/benefit.

Differences between this summary and other sources

Our summary is in agreement with the only systematic review identified.
We did not identify guidelines that are recognized by a substantial proportion of experts in the topic.

Could this evidence change in the future?

The probability of this information changing with new studies is very high because the certainty of the evidence is very low.
Unfortunately, we did not identify any ongoing study addressing this question.

How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Matrix of evidence (static version)

Follow the link to access the interactive version Corticosteroids plus azathioprine versus corticosteroids alone for polymyositis

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

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