Background/Purpose:

Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment. Limitations of systemic exposure of oral MTX can affect its efficacy. Subcutaneous (SC) MTX improves bioavailability, which may result in better efficacy, and tolerability. Self-administration of SC MTX via conventional vial and syringe is challenging for some patients due to injection-associated anxiety, functional limitations, injection-site adverse events (AEs), and especially pain. An investigational auto-injector that delivers SC MTX was tested with the intention of addressing these patient concerns.

Methods:

 101 RA patients were enrolled in this phase 2, multi-center, open-label, single-dose, single-arm, in-clinic study to evaluate the actual human use of SC MTX administered via a developmental MTX auto-injector (MTXAI). MTX dose (10, 15, 20, 25 mg) was determined by investigators based on patient MTX regimen and disease status (controlled or uncontrolled) at time of enrollment.

Results:

 99 patients were evaluable. (79.2% female, mean age 60.9 yrs. [SD± 10.1], mean disease duration 13.3 yrs. [SD± 11.0], 84.2% ACR Class II or III, 89.1% Functional Class II or III). All patients had been taking MTX for ≥3 months prior to study enrollment; 20% had used SC MTX. Safety was assessed by recording AEs and evaluating administration sites before and at 0.25, 1, 6, and 24 hours after self-administration. Administration site pain (measured on a 100-mm VAS) is summarized in the table. Mean administration site pain was 3.6 mm/100 mm [SD± 9.1] on Day 1 with a median 1.0 mm/100 mm (0-72) and a mean of 1.4 mm [SD± 3.2] with a median of 0.0 mm (0- 21) on Day 2.  93/99 pts. (94%) reported VAS scores of ≤10 on Day 1; 86/99 pts. (87%) reported scores of ≤5 on Day 1. Of 404 post-administration evaluations, 92.3% found no erythema. The remainder indicated “very slight, barely perceptible” erythema. Three patients had AEs (sick sinus syndrome, exostosis, and headache) not considered related to the study drug by the investigators. 100% of patients, including those with moderate-to-severe functional limitations in dexterity, successfully used the auto-injector.

Table. Administration site pain and erythema (Scale 0-100mm)

SD = standard deviation

Conclusion:

 The MTXAI was well tolerated with almost no administration site pain and minimal erythema. Limitations in functional status did not affect ability to self-administer. Improving the delivery of SC MTX with this developmental, first-in-class auto-injector may increase patient tolerance of self-injection thereby improving adherence in patients with RA.