Background/Purpose: Drug discontinuation rates are measures of effectiveness and are needed in health economic models. While a recent RCT demonstrated statistical equivalence of efficacy with etanercept [1], little is known regarding the real-world use and discontinuation rates of triple therapy, which includes methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ).

Methods:

We evaluated the treatment discontinuation rates of triple therapy in rheumatoid arthritis using a large observational cohort, the National Data Bank for Rheumatic diseases. We initially defined discontinuation as when all 3 DMARDs (MTX, SSZ & HCQ) were not taken (First). Since we cannot verify if triple therapy was purposely prescribed, our second discontinuation definition occurred when the patient was no longer on any combination of the 3 DMARDs or if they added a biologic (Second). In both cases missing data between periods on triple therapy were assumed to remain on treatment. Kaplan-Meier survivor functions were used to analyze discontinuation rates.

Results: From 10,156 patients on biologics and DMARDs, 388 (3.8%) initiated triple therapy at some point between 1998-2012. From these 304 (78.4%) discontinued triple therapy according to our first definition with 121 (39.8%) immediately switching to or adding another DMARD while 183 (60.2%) dropped one or two of the 3 drugs. A total of 216 (55.7%) discontinued according to our second definition.  The discontinuation rate of triple therapy by our two definitions were 40.8% (First) and 23.5% (Second) per year (See Table). The median survival on triple therapy was 14 months (IQR 6-45 months), and doubled to 28 months (IQR: 10-112 months) when using the second definition. At 24 months, the discontinuation rates were: 39.1%  (95% CI 33.9%- 44.2%) and 53.4% (95% CI 48.2%- 59.0%), for first and second definitions respectively. After triple therapy, patients tended to switch/add more DMARDs afterwards (59.3%) than biologics (41.2%).

Conclusion: This is the first study to provide discontinuation rates of triple therapy using community experience in the biologic era. Overall discontinuation rates were high and patients tended to switch between several combinations of MTX, SSZ, and HCQ. Future work is needed to identify rates of prescription and patient/physician preferences for triple therapy.

[1] O’Dell JR et al. Therapies for Active Rheumatoid Arthritis after Methotrexate Failure. N Engl J Med. 2013

Table.  Discontinuation rates and median survival for patients on triple therapy.
	Discontinuation Definitions
	First – Strict	Second – Relaxed
Time at risk (patient years)	742.2	918.0
Discontinuation rate per year	0.408	0.235
Median survival (months)	14	28
Discontinuation rates  (95% CI) after:
1 year	0.501 (0.449, 0.551)	0.627 (0.621, 0.719)
2 years	0.391 (0.339, 0.442)	0.538 (0.482, 0.590)
3 years	0.291 (0.242, 0.343)	0.438 (0.381, 0.494)

---

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/discontinuation-rates-in-patients-with-ra-of-triple-disease-modifying-antirheumatic-therapy/