Dose, Duration of Methotrexate Treatment May Be Linked to Lung Impairments in JIA Patients

Dose, Duration of Methotrexate Treatment May Be Linked to Lung Impairments in JIA Patients

Treatment with methotrexate, an immunosuppressive therapy, may be linked to a decline in lung function in children with juvenile idiopathic arthritis (JIA), a study suggests.

The study, “Lung function in children with juvenile idiopathic arthritis: A cross‐sectional analysis,” was published in the journal Pediatric Pulmonology.

Research suggests that from 4% to 8% of patients with JIA, especially those with systemic-onset JIA, have serositis (inflammation of serous membranes), such as the pleura, the membrane that surrounds the lungs. This may lead to impaired lung function.

However, it is still unclear whether such impairments are due to a decline in lung function or to the use of immunosuppressive therapy, such as methotrexate, currently the recommended first-line treatment for JIA.

A prior study suggested that prolonged use (more than three years) of methotrexate correlates with decline in lung function in JIA children. However, the impact of methotrexate on lung function is still a matter of debate.

Researchers at the University of Chieti, Italy, now measured parameters of lung function in a group of 49 JIA children (mean age 13 years) without clinical signs of respiratory involvement and compared it to that of 70 healthy participants used as controls. Moreover, they assessed the impact of methotrexate treatment and disease activity on lung function.

Children with JIA were divided into two subgroups: one group (21 children) was undergoing treatment with methotrexate (group A); the remaining 28 children were taking biological therapies. Seven were on etanercept (sold under the brand name Enbrel, among others), one on adalimumab (sold under the brand name Humira, Exemptia, and others) and one on anakinra (Kineret), or nonsteroidal anti-inflammatory drugs (NSAIDs).

Researchers assessed lung function by evaluating several parameters, including; forced expiratory volume in 1 second (FEV1) — how much air a person can exhale during a forced breath in the first second; forced vital capacity (FVC) — the amount of air one can exhale after inhaling as deeply as possible; and diffusing capacity for carbon monoxide (DLCO) – a specific measure of lung function that assesses the lungs’ capacity to transfer oxygen from the air sacs into the blood.

The results showed that the only lung parameters that significantly changed between JIA children and healthy controls was DLCO. JIA children had a lower DLCO score (87%) than controls (99%).

Moreover, when comparing children who were taking methotrexate (group A) to those receiving other treatments (group B), researchers saw that those in group A had a significant reduction in DLCO values compared to those in group B (77% vs 96%, respectively).

A significant difference in DLCO also was found among JIA patients with active disease (82%) and those with inactive disease (97%) and healthy controls (99%).

“Importantly, we found a higher percentage of patients with active disease in group A compared with group B (90.9% vs 40.7%),” the researchers wrote.

Further analysis revealed a significant correlation between lower DLCO values and increasing doses of methotrexate as well as treatment duration.

Overall, these results suggest that in children with JIA, even in the  absence of symptoms of pulmonary involvement “[methotrexate] treatment seems to have a dose-dependent effect on lung function,” the researchers wrote.

“For this reason in these patients, a regular assessment of lung function, especially with DLCO evaluation, is recommended,” they concluded.

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