UK Health Assessment Study: Older Drug Combos Equal TNF Drugs for RA

March 23, 2015

The UK government's health assessment agency has found that combinations of traditional drugs offer results for rheumatoid arthritis not inferior to those of tumor necrosis factor inhibitors, although the latter work more quickly.

Scott DL, Ibrahim F, Farewell F, et al. Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial. BMJ 2015; 350  doi:

Miossec P. Editorials: Drug treatments for rheumatoid arthritis: looking backwards to move forwards. BMJ 2015; 350 (13 March 2015) doi:

A UK study has found that that the older drugs are non-inferior toTNF inhibitors when methotrexategaveinadequate control of rheumatoid arthritis (RA).  

Other randomized, controlled trials have concluded that the addition of sulfasalazine and hydroxychloroquine is non-inferior to the addition of tumor necrosis factor (TNF) inhibitors such as etanercept, although some rheumatologists say that those studies don’t square with their personal experience. (See MTX Fails in RA. What Next? Reviewers Respond.)

The TNF inhibitors Against Combination Intensive Therapy (TACIT) study was funded by the UK National Institute for Health Research Health Technology Assessment.

In the TACIT study, 205 patients who were eligible for treatment with TNF inhibitors under current English guidance were randomized to either a TNF inhibitor first strategy or a combined disease modifying drug first strategy. For non-responders, additional drugs, including TNF inhibitors, were added after six months.

The TNF inhibitors were adalimumab, etanercept, and infliximab, following local practice. The most common TNF inhibitor was adalimumab and the most common drug combination was methotrexate and leflunomide.

The primary outcome was reduction in disability at 12 months, measured by a patient-recorded health assessment questionnaire (range 0-3), with a 0.22 non-inferiority margin. Baseline scores were 1.9 (TNF inhibitor first group) and 1.8 (combined drug group). The change in scores over 12 months was -0.30 (TNF inhibitor first group) and -0.45 (combined drug group). The mean difference was -0.14, which was below the prespecified non-inferiority margin.

The initial reductions were greater in the TNF inhibitor first group, which indicates the rapid onset of TNF inhibitors, but that difference disappeared by 12 months.

The editorial says that we should not call both treatments equally good; we should call them equally bad. Current treatment regimens start too late. If we were to follow the model of cancer treatments, we would combine drugs at the start of treatment and not wait for traditional monotherapies to fail.