Background Glucocorticoids (GC) are used to treat a wide range of inflammatory diseases including rheumatic and musculoskeletal diseases. EULAR recommendations on GC therapy are up to date but uncertainty about the benefit-risk ratio of GC persists. To address this issue, a multidisciplinary EULAR task force was assembled.
Objectives Bearing in mind the known beneficial effects of GC, the primary aim was to achieve consensus when formulating conditions under which these drugs have a good benefit-risk ratio, based on systematic evaluation of available evidence on adverse effects (AE).
Methods Focussing on the four most worrisome AE of GC (cardiovascular disease (CVD), effects on bone, GC-induced hyperglycaemia & diabetes mellitus and infections), a systematic literature review was performed and discussed in the expert group. One breakout group per AE discussed the relevant evidence in detail and presented their results to the other group members following a structured questionnaire for final discussion. The questions addressed dose-harm relationships, relevant patient characteristics, co-morbidities, co-medications and both preventive and therapeutic measures with regard to the AE mentioned above.
Results The common basis for the group's work was (i) an initial agreement with current guidelines stating there is convincing evidence for the beneficial effects of GC also at low dosages and (ii) the view that data on AE are limited (e.g. in terms of duration of GC use), sometimes both contradictory and biased. As a result of the critical appraisal of available evidence, the task force members agreed that for the majority of patients:
– at dosages of ≤5mg/d prednisone equivalent the benefits are greater than the risks with the exception of patients at high risk for CVD who may require preventive measures
– at dosages of >10mg/d the risks are greater than the benefits, with the exception of patients with (partial) GC resistance.
At dosages between >5 and ≤10mg/d, the benefit-risk ratio depends on patient-specific characteristics such as disease activity, presence of additional risk factors, and preventive measures. In general, an early diagnosis, low disease activity, low cumulative GC dosage, healthy life style (including appropriate exercise) and both, monitoring and treatment of risk factors and co-morbidities, respectively, represent factors which reduce the risk, thereby improving the benefit-risk ratio. For each AE of GC, specific factors can affect the risk and, therefore, the benefit-risk ratio in both directions. Moreover, for some GC induced AE (i) specific patient groups are at higher risk, (ii) certain co-morbidities increase the risk and (iii) the genetic background and (iv) specific disease characteristics may have impact on the benefit-risk ratio. Thus, the benefit-risk ratio varies between individuals, and consequently our consensus is valid for the majority of patients rather than every individual patient.
Conclusions There is no absolute condition or conditions under which GC always have good benefit-risk ratios. However, based on currently available evidence, our consensus provides the rationale to accomplish a relatively safe use of GC in the majority of patients.
Disclosure of Interest C. Strehl: None declared, J. Bijlsma: None declared, M. de Wit: None declared, M. Cutolo: None declared, R. Sereor: None declared, K. Winthrop: None declared, F. Buttgereit Grant/research support from: Merck Serono, Horizon Pharma, Consultant for: Merck Serono, Horizon Pharma,Mundipharma International Ltd., Pfizer
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.