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These are additive mechanisms, not opposing ones, which is why the combination is biologically coherent even if direct clinical trial data remain sparse

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Although methotrexate didn’t improve heart health, it was associated with several troubling side effects compared to placebo, including: A 23% higher rate of gastrointestinal (GI) symptoms, such as nausea and vomiting A 42% higher rate of lung problems, including cough, trouble breathing and in a small percentage of people, pneumonitis, a potentially fatal lung inflammation A 15% increase in infections A doubled risk of skin cancer, although the overall rate was low Two kinds of side effects can occur in children who take methotrexate for JIA: symptoms, particularly nausea and vomiting, caused by the drug itself and by anticipating taking it