Up to our best knowledge, currently there are no studies assessing the features of drug delivery systems important for patients with JIA and their caregivers. Studies conducted among individuals with RA showed the preference for subcutaneous injections in comparison to intravenous infusions and tendency to select ready to use drug delivery systems, with a high preference for pen autoinjectors [13-17]. Moreover, the risk of side effects associated with treatment method was not neglectable [18]. Currently, MTX is available in Poland in two forms: oral pills and subcutaneous prefilled syringes. The parenteral way of MTX administration is preferred by clinicians, as it provides dependable efficacy, predictable bioavailability, sustained clinical outcomes, and lower risk of adverse effects [19,20]. Nevertheless, the caregivers are frequently reluctant to this method of treatment, usually due to the pain associated with injection and low level of self-confidence regarding the device proper use. The newly developed prefilled pen may become a long-awaited solution to this problematic issue.
In our study, we have assessed the overall patients and caregivers preference for MTX pen as 82.6%. Despite the small size of the study population, the results are comparable to those obtained in patients with RA, where the preference for pen reached 75% [9]. Interestingly, despite our patients received the prefilled syringe treatment for a considerably longer period than the prefilled pen, their caregivers have evaluated the latter device as easier to use (p<0.01). Moreover, it corresponded to the higher level of their self-confidence regarding the device proper use (p<0.01).
Pain associated with the drug administration is a significant drawback of treatment, especially pronounced in the pediatric population. In our study, the injection performed with the prefilled pen was reported as less painful both by patients and their caregivers.
Those results are contradictory to the outcomes of the study performed in RA patients, although those findings are not directly comparable as different measures (Self-injection Assessment Questionnaire [21] in RA patients) were applied when assessing this parameter.
The frequency of gastrointestinal side effects during MTX pen and syringe treatment was not evaluated in the previous studies. In our patients’ nausea, vomiting and abdominal pain were significantly less pronounced during the treatment with MTX pen (p<0.01), although the dosage of the drug was not changed during the examination period and drug pharmacokinetic properties were assessed as comparable during treatment with similar devices in previous studies [22]. This finding implies that the vast majority of gastrointestinal MTX adverse effects present in the pediatric population may not be the effect of drug toxicity itself, but the result of a stress reaction to the injection process. The MTX pen is equipped with a special needle cover system, which was constructed in order to diminish the risk of caregivers’ needlestick injury. What is more, the invisibility of the needle during the injection may lead to a lower level of stress and pain associated with the drug administration in the children with JIA [23].
Although very promising, the results of our study must be interpreted with caution and a number of limitations should be borne in mind. To begin with, it was a pilot study, conducted on relatively small study group with low representation of children administrating MTX by themselves (3/23, 13.1%). In consequence, the overall preference of MTX autoinjector and frequency of treatment side effects was assessed by the caregivers in 20/23 (86.9%) children and therefore may not reflect the actual opinion of patients themselves. However, we consider this limitation as unlikely to influence our results, as pain level which was assessed both by children (FPS-R) and their caregivers (FLACC) was similar, suggesting that the observation of a caregiver reflects well the opinion of their child. Moreover, the JIA patients enrolled to this project were already treated with subcutaneous MTX in the form of prefilled syringe. Thus, the impact of new autoinjector novelty effect on our results can not be excluded. Future studies, including larger group of subcutaneous MTX-naive JIA patient and enriched with the assessment of the injection process by both patient and caregiver conducted in the crossover design are needed to verify our findings.