Background/Purpose:

Methotrexate (MTX) monotherapy or MTX in combination with other conventional and biologic disease-modifying antirheumatic drugs (DMARDs) is standard treatment for patients with inflammatory arthritis. A significant number of patients discontinue therapy with oral (PO) MTX because of intolerance or a lack of efficacy. Standard practice at our institution involves switching such patients to subcutaneous (SC) MTX prior to the addition of other agents. This study was designed to assess the therapeutic outcomes of this approach in the outpatient setting.

Methods:

We retrospectively reviewed electronic medical records within our patient cohort from 2001 to the present, and included patients who switched from PO to SC MTX. Records were analyzed for baseline demographics, reasons for switching to SC MTX, doses of PO and SC MTX at the time of the switch, duration of SC MTX use, reasons for discontinuation of SC MTX (if applicable), and whether the addition of biologic agents was required. 

Results:

The records of 240 patients who switched to SC MTX were examined. Fifty-eight patients were excluded because of incomplete data. Of the 182 patients included, 125 (68%) were female, and the average age at starting SC MTX was 52.5 years (range 17-82). Underlying diagnoses included rheumatoid arthritis (n=144), psoriatic arthritis (n=20), juvenile idiopathic arthritis (n=7), ankylosing spondylitis (n=2), undifferentiated inflammatory arthritis (n=6), systemic lupus erythematosus (n=1), and vasculitis (n=2). Reasons for switching from PO to SC MTX included intolerance (n=55), inefficacy (n=118) and unknown (n=9). One hundred ten patients (60%) were receiving no other DMARDs at the time of the switch. In the majority of the remaining patients (n=60), MTX was used in combination with sulfasalazine (n=21), hydroxychloroquine (n=21), prednisolone (n=11), leflunomide (n=4), or anti-tumor necrosis factor-α therapies (n=3). At the time of switching patients were taking an average dose of 20mg/week PO MTX and were switched to an average dose of 15mg/week SC MTX (range for both 5-25mg/week). One hundred thirty-three (73%) patients remain on SC MTX to date; 49 patients discontinued SC MTX because of intolerance (n=26), adverse drug reaction (n=10), inefficacy (n=6), disease remission (n=2), or undocumented reasons (n=5). Thirty-nine percent of those who discontinued SC MTX required the addition of a biologic, compared with 28% of those who continued with SC MTX. Sixty-five percent of those who switched to SC MTX because of intolerance were able to continue with this drug, for an average duration of 46 months (range 2-144 months) to date; 40 to 45% of those who switched to SC MTX because of intolerance or inefficacy, respectively, did not require the addition of another DMARD or biologic agent. 

Conclusion:

This evidence strongly supports the use of SC MTX as a tolerable and efficacious alternative after failure of PO MTX. After the switch to SC MTX, 65% of patients who were intolerant of PO MTX continued with MTX, either as monotherapy or in combination with other DMARDs or biologic agents. Furthermore, patients who continued with SC MTX were less likely to require biologic agents. Further evaluation of this approach may be warranted.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-tolerability-of-subcutaneous-methotrexate-for-inflammatory-arthritis-a-retrospective-observational-cohort-study/