Do snapshot statistics fool us in MTX pharmacogenetic studies in arthritis research?

Early predictors of prognosis in juvenile idiopathic arthritis: a systematic literature review

“…To avoid variability, the outcome definition should be standardized. Since JIA has a fluctuating disease course,24 40 62 the longitudinal aspect of disease activity should be taken into account. Hence, the best outcome measurement seems to be the cumulative amount of time in CID, CRM or CR.…”

Prediction of clinical non-response to methotrexate treatment in juvenile idiopathic arthritis

“…Our model was constructed for ACR70 non-responders in at least two of three visits during the first year of treatment, due to known fluctuations in MTX (non-)response during the first year 22. Nevertheless, the model had an equally strong predictive power for ACR70 non-responders (AUC=0.71, 95% CI: 0.62 to 0.80) at 6 months after MTX start.…”

“…This definition was used since clinical response to MTX is known to fluctuate in a large proportion of patients between different time points in the first year of treatment 22. MTX non-responders also included patients discontinuing MTX and/or switching to anti-TNFα therapy or other biologicals due to insufficient effect of MTX.…”

Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in patients with rheumatoid arthritis

“…Most of these studies used cross-sectional analyses2 9 10 14 15 in which patients were in different stages of MTX-treatment varying from 3 months to >10 years. Disadvantages of cross-sectional analysis are that you cannot distinguish between those treated for weeks or years and that you cannot make causal inference 16. Additionally, comparison between patients is complicated because MTX is stopped in obstinate non-responders and because MTX-PG accumulation is a function of time 5…”