Background/Purpose:

There is a lack of head-to-head clinical trial data to determine the most effective treatment for rheumatoid arthritis (RA).  However, these trials have had similar patient entry criteria and outcome measures allowing for meta-analysis.  Patients with RA fall into three therapeutic groups: DMARD naïve (no prior exposure to conventional or biologic disease-modifying-anti rheumatic drugs [DMARD]), Biologic naïve (prior exposure to conventional DMARDs but not biologic DMARDs) and Biologic second-line (prior exposure to biologic DMARDs).

A decision analysis was designed to identify an optimal treatment strategy for DMARD naïve patients with RA.

Methods:

A total of 270 studies were identified on ClinicalTrials.gov and Medline, of which 193 were eliminated in the abstract review phase.  Seventy-seven studies were screened in full text and seventy were excluded for reasoning including lack of randomization, uncertain diagnoses, and non-standard treatment.  Seven clinical trials were included for the DMARD naïve group corresponding to twelve treatment options.

The treatment options included placebo, methotrexate, biologic drugs alone and methotrexate plus biologic drugs.  Drug effectiveness was measured by the ACR 20 and ACR 50 criteria and the rate of serious adverse events was modeled across different therapeutic options. Sensitivity analyses were conducted for probability of serious adverse drug reactions and the ACR 20 and ACR 50 effectiveness measures. 

Results:

In the biologic drugs group alone, treatment with etanercept 25mg bi-weekly resulted in the maximum quality-adjusted-life-year (QALY) gain of 23.24 years compared to placebo at 21.55 years (1 year and 8 months) and methotrexate at 22.12 years (1 year and 1 month).  In the methotrexate plus biologic group, treatment with etanercept 50mg plus methotrexate resulted in 23.20 QALYs. Adalimumab 40mg (21.79 QALYs), Infliximab 3mg plus methotrexate (21.83 QALYs) and triple therapy (21.76 QALYs) resulted in the lowest QALY gain.

Sensitivity analysis showed at ACR 20 success criteria etanercept alone is preferred, while at ACR 50 criteria etanercept plus methotrexate is the preferred treatment option. At base case methotrexate was not a preferred treatment, however if methotrexate’s ACR50 response rate exceeds 34% then it would become the optimal treatment strategy if all other factors were held constant. By contrast, treatment with etanercept 25mg on a bi-weekly basis and etanercept 50mg plus methotrexate are no longer the favored treatment options if their adverse drug reaction rates increase from 6% and 12% to 9% and 13% respectively. 

Conclusion:

Biologic therapy alone and biologic therapy plus methotrexate appear to be the favorable treatment strategies for the DMARD naïve group. The QALY gains for biologic therapy in rheumatoid arthritis are similar to that of biologic therapy in psoriasis and interferon therapy for multiple sclerosis (0.20-3.3 QALYs). The decision depends in part on the side effect profile and costs.  Decision aids to elicit patient preferences and drug costs may override differences in drug effectiveness.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/is-there-an-optimal-treatment-strategy-for-disease-modifying-antirheumatic-drug-naive-patients-with-rheumatoid-arthritis/