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To the Editors:

We thank Rider et al for their interest in our work and for their stimulating comments. Although children/adolescents and adults with DM share many signs and symptoms of disease, they differ in the frequency and severity of some manifestations, and moreover, physical/mental age-related issues that are related to growth and development have to be taken into account. Therefore, it cannot be assumed a priori that the clinical measures developed for adults are suitable for children and adolescents. Consequently, in our opinion, all outcome measures developed for adults need to be subjected to a critical evidence-based evaluation of their measurement properties in children and adolescents (1–3). We concentrated our work just on juvenile DM because it constitutes by far the majority of all forms of childhood myositis.

We do not agree with Rider et al that our study is a natural history study; rather, it represents a prospective study that closely mimics the design of a clinical trial, having enrolled patients in the active phase of the disease at the time of a major therapeutic intervention. Indeed, clinical trials are usually performed in 2 different types of populations: for new agents for which safety information is scarce, and usually patients who are refractory to any given treatment and have accumulated disease damage are enrolled; whereas for agents with greater safety information, patients with shorter disease duration are enrolled with the idea to prevent irreversible disease damage. However, for both kinds of trials, disease activity control is always the primary outcome, whereas damage prevention is usually a secondary scope of the trial. This is the reason why the PRINTO researchers have developed a separate core set for the evaluation of disease damage in juvenile DM, the validation of which is ongoing (2).

With regard to the concerns of Rider et al about the risk of a premature selection bias of our work, we have to note that the selection of measures to be included in the preliminary core set have gone through a thoughtful literature review, a careful Delphi selection process involving 222 (80%) of 277 pediatric rheumatologists from 46 different countries, and a nominal group technique-based consensus conference attended by 40 experienced pediatric rheumatologists from 34 different countries, including members of the IMACS group (2).

The preliminary consensus-based core set included serum muscle enzymes (CK, LDH, aldolase, aspartate aminotransferase, and alanine aminotransferase) (4), but none of them, including LDH, was able to be retained in the provisional PRINTO/ACR core set, not only for the small responsiveness, but also for the lack of construct validity, discriminant validity, and internal consistency. Another possible explanation for their low statistical performance relies on the fact that physicians incorporate the results of muscle enzymes into their composite evaluation of the child's overall disease activity status.

We agree that several measures performed comparably in their responsiveness, discriminant validity, construct validity, etc., and this is exactly why the PRINTO/ACR provisional core set indicates 5 key domains and only suggests the variables to measure each domain. This was purposely done to leave the choice of the most appropriate measures to researchers (e.g., the CMAS or MMT for muscle strength evaluation and the DAS or MITAX as global disease activity tools).

The authors also pointed out that the PRINTO/ACR provisional core set has 2 redundant measures (the CMAS and the C-HAQ with a Spearman's correlation coefficient of −0.71, with the cutoff for redundant measures set to 0.7) and several measures that did not predict a response, but we have to note that the selection process is the result of both statistical and consensus-based evaluations.

We did not understand the criticism that the PRINTO/ACR provisional core set has few measures that would discriminate disease activity from damage. To the best of our understanding, the IMACS core set, which is remarkably similar to ours, does not include such measures either, nor does it include health-related quality of life measures that will be able to reflect severe disease damage, such as in the case of a child with extended calcinosis or severe cutaneous damage.

Another difference between the IMACS and PRINTO/ACR core sets is the fact that IMACS, as a multidisciplinary group, maintains the MMT as a measure of muscle strength, whereas the CMAS is considered a measure of muscle endurance and physical function. In our prospectively based data collection, the CMAS and the MMT showed a higher redundancy than the CMAS and the C-HAQ (r = 0.77 versus 0.71), suggesting, as for the similar responsiveness, that they are interchangeable measures of muscle strength and not physical function.

Finally, we agree with the IMACS group that the 2 core sets are conceptually closely related (assuring convergent validity of the 2 efforts) and provisional until further validation in a different data set, and we also welcome future opportunities to work together with the IMACS group, as has been done in the past. The endorsement of the PRINTO core set by the ACR/EULAR committee is simply as an extra independent review that witnesses the validity of our scientific approach.

  • 1
    Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A. Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 1997; 40: 12029.
  • 2
    Ruperto N, Ravelli A, Cuttica R, Espada G, Ozen S, Porras O, et al, for the Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). The Pediatric Rheumatology International Trials Organization criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the disease activity core set. Arthritis Rheum 2005; 52: 285464.
  • 3
    Ruperto N, Ravelli A, Oliveira S, Alessio M, Mihaylova D, Pasic S, et al, for the Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the definition of improvement. Arthritis Rheum 2006; 55: 35563.
  • 4
    Rider LG, Miller FW. Laboratory evaluation of the inflammatory myopathies. Clin Diagn Lab Immunol 1995; 2: 19.

Nicolino Ruperto MD, MPH*, Angela Pistorio MD, PhD*, Angelo Ravelli MD†, Alberto Martini MD†, * IRCCS G. Gaslini, Italy, † IRCCS G. Gaslini and Universitá di Genova, Genoa, Italy.