After the 1st TNF Inhibitor, a Non-TNF Biologic is Next Best Save

Most US rheumatologists use 2, and sometimes 3, TNF inhibitors (TNFi) before switching to a biologic targeting another mechanism (MOA).  There are a growing number of trials showing that after failing a first TNF inhibitor (especially with primary failures) it may be prudent to change to the "other-MOA" biologics.

300 patients with active RA (DAS28 >3.2) were enrolled after failing their first TNFi (for an insufficient response) and were randomized to receive open label treatment with either a second TNFi (adalimumab, certolizumab, etanercept, infliximab, or golimumab) or a non-TNF biologic (ie, abatacept, rituximab, or tocilizumab) for 52 weeks. The choice of the biologic prescribed within each randomized group was left to the treating clinician.

The primary endpoint was the percentage of patients achieving a good EULAR response (defined as a decrease in DAS28-ESR of more than 1.2 points, resulting in a score of 3.2 or less).

Of the 300 randomized patients, 269 (90 percent) completed the study. At week 24, 101 of 146 patients (69 percent) in the non-TNF group and 76 (52 percent) in the second anti-TNF group achieved a good or moderate EULAR response.

The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group. At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45 percent vs 28 percent at week 24; and 41 percent vs 23 percent at week 52; (P = .003).

“Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but considered for a second medication due to inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks. However, a second anti-TNF drug to treat these patients was often effective in producing a clinical improvement,” the authors conclude.

These data (and others) strongly argue against the practice of sticking with another TNFi after the first failure.  On the other hand, there are no clear indicators as to which of the other non-TNFi biologics would be best in this situation.