Background/Purpose: A recent US-study suggests considerable underuse of MTX and too early switches to biologic (b)DMARDs¹  before using a high MTX dose or changing the route of administration. We investigated doses of MTX, route of administration and time to treatment escalation with bDMARDs in Germany.

Methods: The biologics register RABBIT (Rheumatoid Arthritis: Observation of biologic therapy) comprises a control group of patients who were enrolled when starting csDMARDs after failure of at least one csDMARD therapy (mostly MTX monotherapy). We selected n=1,608 patients starting either with MTX monotherapy, MTX + another csDMARD or triple therapy (MTX plus hydroxychloroquine and sulfasalazin). In a sub-cohort of patients recruited between 2009 and 2013 (n=1,151) information about the route of administration was available.

Results:  1,210 patients (75.2%) were enrolled at start of MTX plus another csDMARD, 356 patients (22.1%) starting MTX monotherapy and 42 patients (2.6%) with triple therapy. The proportions of male and seropositive patients were higher in MTX combination and triple therapy (p<0.05). Disease severity (DAS28) at baseline and physical function were not significantly different. Larger differences were found in the sub-cohort: patients treated with subcutaneous (sc) MTX were significantly younger, had a higher DAS28, higher doses of glucocorticoids (GC) and less physical function at baseline (p<0.01).

Overall, 266 (16.5%) patients were escalated to a bDMARD within the 1^st year of observation. Only 53 patients (3.3%) switched to a bDMARD within 3 months after enrollment; without an impact of calendar time (p=0.23). In recent years, escalation to bDMARD therapy occurred earlier (Fig. 1). The median time to a bDMARD was highest (p<0.01) in MTX monotherapy (366d) compared to MTX combination (266d) and triple therapy (150d).

In year one, the average doses of MTX did not vary between the treatment regimens: MTX mono (15.2mg), combination (15.6mg), triple (15.0mg). In patients who switched to a bDMARD, 28.2% 95%CI [23.0; 34.1] had prior high doses (>20 mg) of MTX and 54.1% [47.9; 60.2] had GC doses ≥5 mg/d which was significantly higher than in patients who maintained csDMARD therapy (MTX >20mg: 17.7% [15.7;19.9], GC ≥5mg: 32.3% [29.8; 34.9]). Stratified by route of administration, doses were significantly higher with sc MTX (16.8mg [16.4; 17.1]) vs. oral (14.8mg [14.5; 15.1]) but more patients (p<0.01) with sc MTX (21.6%) were switched to a bDMARD compared to oral MTX (10.9%).

Conclusion:

Our data suggest that German rheumatologists use different strategies after insufficient response to MTX before switching to a bDMARD: MTX dose increase, change to sc MTX, combination with other csDMARDs or increase in GC dose. The results of the US-study¹ could not be confirmed. 

1 Rohr MK, et al. "The Underuse of Methotrexate in the treatment of RA: […]" Arthritis Care & Research 2016, Nov 18, epub.