In this work, we have shown that it is possible to achieve consensus on the treatment of JDM, despite considerable variation in clinical practice. We have developed 3 consensus protocols which were intended to reflect current standard initial care of patients with moderately severe typical JDM. We have also established consensus on inclusion/exclusion criteria, initial investigation, follow-up data collection and concomitant medications, facilitating future evaluation of these protocols.
Despite its acknowledged value and ubiquitous use, the use of corticosteroids in the treatment of JDM has never been studied in a randomized controlled trial (RCT). In fact, there have been almost no RCT's of any medications in JDM. The explanation for this is largely related to the rarity of JDM (incidence of 2-4 cases per million per year [7
]), but also to the difficulties in studying this complex disease and the lack of tools with which to measure outcome. Recent efforts have largely eliminated the latter issue. There are now a variety of tools that have been shown to be valid assessments of muscle function [8
], skin disease activity [11
], extra-muscular disease activity [13
] and overall disease activity [13
]. Unfortunately, researchers are still left with the challenges presented when studying a rare illness.
In order to improve outcomes in JDM and minimize both morbidity and mortality, it is necessary to optimize currently available therapeutic regimens, and to evaluate new medications which may become available. It will be difficult for traditional RCT's to achieve these goals because of the small number of patients available for study and the costs associated with conducting clinical trials which must include large numbers of centres and encompass vast geographic areas.
Development of these protocols is a first step in beginning to study treatments in JDM using a new approach. We envision a study where treating physicians could choose the protocol which most closely reflected their typical treatment of patients with moderately severe JDM. By collecting data in a standardized fashion, data could be pooled from multiple physicians, who are all engaging in routine care decisions. These data could then be analyzed using statistical methods which account for variations in illness severity and other factors measured at baseline which may influence outcomes (confounding by indication) [17
]. In this way, these protocols could be compared without the expense and complexity of infrastructure that would be required for an RCT. However, this assumes that it is possible to ensure that similar patients are being compared, and that differences between patients are accounted for. All important disease and patient characteristics would need to be measured. Advances in statistical methods (such as propensity scoring and other techniques) and development of a variety of validated measurement tools in JDM make this less problematic. However, it remains to be seen whether this type of analysis will ultimately be successful.
Our work should be interpreted in the light of potential limitations. Although these protocols should be similar to treatment decisions made by most pediatric rheumatologists, they cannot represent all possible options. For example, the initial use of hydroxychloroquine or cyclosporine is not addressed, as these medications were not as widely used in the CARRA survey. As well, data and expert opinion used in this project were primarily derived from North American pediatric rheumatologists. This may mean that not all pediatric rheumatologists will be able to identify a protocol which is similar to their usual practice. However, the protocols should have wide enough applicability to allow their evaluation. Finally, new data is emerging that there may be more sensitive, immunologically-based indicators of continued disease. These were not included in our consensus discussions, but may one day play a role in determining therapy.
It should be emphasized that these treatment protocols are not intended as treatment recommendations. They have been chosen to reflect care provided by clinicians. Given the near complete lack of clinical trial data, it is not clear if one of these protocols is the optimal treatment for children with moderately severe JDM. Future research will need to investigate this question.
In conclusion, we have developed three protocols which reflect current treatment of children with moderately severe JDM. These protocols are the first step to allow comparison of different approaches to the treatment of JDM. In order to achieve this goal, future work will need to extend the treatment protocols beyond the initial period, develop a plan for data collection and develop methods to account for differences between patients in whom these protocols are used. Subsequently, the protocols will need to be further updated as new medications or treatment approaches become available.