TNF inhibitors restore normal growth rates in JIA

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TNF inhibitors restore normal growth rates in JIA



Feb 14, 2006



Janis

Helsinki, Finland - TNF inhibitors not only reduce inflammation but

also restore growth velocity in patients with juvenile idiopathic

arthritis (JIA), and those children with the worst growth delays gain

the most from treatment. Dr Pirjo Tynjala (Helsinki University

Central Hospital, Finland) reports the data on growth of JIA patients

in a paper published online January 31, 2006 in ls of the

Rheumatic Diseases [1].

" When the growth was calculated as cm/year, the growth rate increased

by +1.8 cm/year in the patients with previous delayed growth, "

Tynjala reports.

" In many of the patients responding well to the anti-TNF therapy,

previously delayed growth was not only partly but totally restored.

The duration of disease may play a part in the grade of the

restoration, but how much we were not able to count in this setting, "

Tynjala told rheumawire.

Decreased inflammation permits increased growth



When the growth rate was calculated as cm/year, the growth rate

increased by +1.8 cm/year in the patients with previous delayed growth.





The investigators analyzed growth of 71 JIA patients over four years:

two years before beginning TNF-inhibitor treatment and two years

after treatment initiation. At the time treatment began, patients

were a mean age of 9.6 years and had mean disease duration of 5.7

years. Of the patients, 43 were on etanercept (Enbrel, Amgen/Wyeth)

and 28 were on infliximab (Remicade, Centocor). All had severe

polyarticular disease and were refractory to conventional disease-

modifying antirheumatic drugs (DMARDs).

Growth velocity increased significantly (p<0.001) during TNF-

inhibitor treatment in 53 children who had delayed growth at

baseline. The 18 children with normal growth at baseline did not have

significant changes in growth during TNF-inhibitor treatment.

Growth was measured as the change in height standard-deviation score

(SDS) for age and gender. The growth velocity was defined as the

change in height SDS during the follow-up period. The researchers

also measured height-adjusted relative weight and body-mass index.

They used the Greulich-Pyle method to estimate skeletal maturation

relative to that of normal Finnish children.

Multiple regression analysis identified growth velocity before the

initiation of TNF inhibitors, cumulative steroid dose, erythrocyte

sedimentation after two years of TNF inhibition, and cumulative intra-

articular steroids as predictors of the change in growth velocity.





The improvement in the growth velocity may be accounted for by the

decrease in inflammation and not by a direct effect of biological

agents on growth.





The researchers next considered whether the growth improvement might

be due to reduced glucocorticoid intake, reduced inflammatory

activity, or a direct effect on growth processes.

" In our clinical study, the change in the inflammatory activity

remained a significant predictor of the growth velocity even after

glucocorticoids were taken into account. This suggests that the

improvement in the growth velocity may be accounted for by the

decrease in inflammation and not by a direct effect of biological

agents on growth or on skeletal maturation, " they write.

They conclude that treatment of active polyarticular JIA with TNF

inhibitors " not only suppresses inflammation but also restores growth

velocity. "

Tynjala said that the study also raised some new questions for the

investigators.

" Is there a safe dose of glucocorticoids, so that the growth is not

permanently impaired? " he asked. " How early should you start with

anti-TNF therapy? How should you measure the inflammatory activity?

What are the long-term side effects with anti-TNF therapy, and are

there adverse effects we should be watching out for? Are there

contraindications against continuation of TNF blockers throughout the

growing period? "



Source



Tynjala P, Lahdenne P, Vahasalo P, et al. Impact of anti-TNF therapy

on growth in severe juvenile idiopathic arthritis. Ann Rheum Dis

2006; DOI:10.1136/ard.2005.047225. Available at: http://

ard.bmjjournals.com. 

http://www.jointandbone.org/viewArticle.do?primaryKey=648391