Tocilizumab a suitable alternative to TNFi for RA treatment

The biologic disease-modifying antirheumatic drug (bDMARD) tocilizumab (TCZ), used alone or with concomitant conventional synthetic (cs) DMARDs, is an adequate alternative to a TNFi*-csDMARD regimen in patients with rheumatoid arthritis (RA), results from the TOCERRA** initiative show.

The TOCERRA collaboration comprised data of 11,505 RA patients from seven European registries who are naïve to bDMARDs and targeted synthetic (ts) DMARDs. The effect of tocilizumab was compared against TNFis, either as monotherapy (mono) or in combination with csDMARDs (combo), listing four treatment arms: TCZ-mono (n=384), TCZ-combo (n=646), TNFi-mono (n=3,762), and TNFi-combo (n=6,713). [Semin Arthritis Rheum 2020;50:17-24]

After adjusting for confounders***, compared with the TNFi-combo arm, discontinuation rates were significantly lower in the TCZ-mono and TCZ-combo arms (hazard ratio [HR], 0.60, 95 percent confidence interval [CI], 0.52–0.69 and HR, 0.66, 95 percent CI, 0.54–0.81) and substantially higher in the TNFi-mono arm (HR, 1.24, 95 percent CI, 1.13–1.36; p<0.001 for all).

These findings suggest that drug retention was longer with TCZ, be it alone or in combination with csDMARDs, said the researchers. “[H]owever, the exact reason for this could not be captured precisely in our study,” they pointed out. Based on previous evidence, potential reasons for the longer drug retention for TCZ were better efficacy and tolerability or the lack of suitable alternatives following multiple bDMARD failure. [Rheumatol Ther 2018;5:507-523; Ann Rheum Dis 2018;77:1276-1282]

CDAI, DAS-28

At 1 year, attrition-corrected analysis using LUNDEX^# revealed similar Clinical Disease Activity Index (CDAI) remission rates across treatment arms (14 to 15 percent). For CDAI low disease activity (LDA) however, the rates were slightly higher in the TNFi-mono arm vs the TCZ-mono, TCZ-combo, and TNFi-combo arms (63.9 percent vs 57.1, 58.3, and 57.0 percent, respectively).

Compared with the two TNFi regimens, both TCZ regimens led to numerically higher Disease Activity Score-28 (DAS-28) remission (45.4/51.2 percent [TCZ-mono/combo] vs 27.1/28.1 percent [TNFi-mono/combo]) and LDA rates (63.2/65.4 percent vs 57.5/47.7 percent).

In the sensitivity analysis excluding patients from the Italian registry^##, LUNDEX-corrected CDAI remission rates were slightly lower in the monotherapy (10 percent [TCZ] and 9 percent [TNFi]) vs the combo regimen arms (15 percent [TCZ-combo] and 13 percent [TNFi-combo]).

“This difference was statistically significant for the TNFi-mono but not the TCZ-mono arm compared with the TNFi-combo arm,” the researchers pointed out, owing to potential differences in baseline patient and disease characteristics. “LUNDEX corrects for attrition but not for baseline characteristics, year of treatment initiation, or country,” they explained. For instance, TNFi-mono patients from the Italian cohort had the lowest baseline disease activity values vs the other arms. “Thus, a higher proportion of CDAI remission in TNFi-mono patients at 1 year is not unexpected,” they said.

Better with biologics

“[I]n clinical practice, bDMARDs and tsDMARDs are usually prescribed only after failing csDMARDs,” said the researchers, hence the current recommendations supporting adjunct bDMARD and tsDMARD therapy. [Ann Rheum Dis 2017;76:960-977] The findings appear to support this, favouring a bDMARD over a regimen comprising TNFis and csDMARDs, they noted.

Despite the nonsignificant findings and lower CDAI remission rates with TCZ-mono in the sensitivity analysis, the collective findings appear to favour TCZ over TNFi should csDMARDs be intolerable or contraindicated, said the researchers.