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Tocilizumab-methotrexate combo shows promise as first-line treatment for early RA

Roshini Claire Anthony
17 Jul 2019

A combination of tocilizumab and methotrexate reduced disease activity at 2 years compared with methotrexate plus prednisone in patients with early rheumatoid arthritis (RA), an effect not demonstrated with tocilizumab monotherapy.

The study was conducted using data from the U-Act-Early* and CAMERA-II** trials where newly-diagnosed (<1 year), DMARD***-naïve patients with RA had been randomized to receive tocilizumab monotherapy (8 mg/kg Q4W), methotrexate monotherapy (starting dose 10 mg/week increased in 5 mg doses up to 30 mg/week or maximum tolerated dose) or tocilizumab plus methotrexate (U-Act-Early); or methotrexate plus prednisone (10 mg/day) vs methotrexate monotherapy (CAMERA-II). In the present study, the researchers analysed the improvements in disease activity and safety in 553 patients treated with tocilizumab with or without methotrexate vs methotrexate plus prednisone.

At 24 months, patients who received tocilizumab plus methotrexate had a lower DAS28# than those who received methotrexate plus prednisone (mean difference, -0.62, 95 percent confidence interval [CI], -1.14 to -0.10; p=0.02). However, there was no significant difference in DAS28 at 24 months between the tocilizumab monotherapy and methotrexate plus prednisone recipients (mean difference, 0.44, 95 percent CI, -1.00 to 0.12; p=0.13). [EULAR 2019, abstract FRI0169; Ann Rheum Dis 2019;doi:10.1136/annrheumdis-2019-215304]

Remission (DAS28 <2.6) at 24 months was greater among tocilizumab plus methotrexate (relative risk [RR], 1.11, 95 percent CI, 1.02–1.22; p=0.02) and tocilizumab monotherapy recipients (RR, 1.09, 95 percent CI, 1.00–1.20; p=0.05) compared with methotrexate plus prednisone recipients.

An analysis conducted after excluding acute phase reactants (APRs) showed a numerically but not significantly elevated Clinical Disease Activity Index (m-CDAI) score at 24 months among patients on tocilizumab plus methotrexate (mean difference, 0.10, 95 percent CI, -0.16 to 0.36; p=0.47) and tocilizumab monotherapy (mean difference, 0.24, 95 percent CI, -0.04 to 0.52; p=0.09) compared with those on methotrexate plus prednisone. However, methotrexate plus prednisone recipients had significantly lower mCDAI scores at 3 months compared with tocilizumab plus methotrexate and tocilizumab monotherapy recipients (mean difference, 0.25; p=0.04 and 0.35; p=0.01, respectively).

Similarly, mCDAI remission (mCDAI <2.8) at 3 months occurred more frequently among methotrexate plus prednisone recipients than tocilizumab plus methotrexate (RR, 0.90; p=0.03) and tocilizumab monotherapy recipients (RR, 0.88; p=0.01) with no significant difference between groups at 24 months (p=0.52 and 0.12, respectively).

“[The mCDAI results suggest that] although tight-control strategies initiating tocilizumab resulted in slightly better mean DAS28 and remission rates compared with … initiating methotrexate with 10 mg prednisone, at least part of these better effects may be due to the specific effect of tocilizumab on APRs,” said the researchers. However, they recommended caution when interpreting the mCDAI results as mCDAI is not a validated tool.

All safety outcomes assessed – incidence of 1 infection, elevation in aspartate aminotransferase or alanine aminotransferase levels, or adverse event-related discontinuation – occurred at similar rates between groups.

Methotrexate plus glucocorticoids is normally the treatment initiated upon RA diagnosis, said the researchers. Due to cost and occasionally, safety concerns, biological DMARDs (bDMARDS) are not usually initiated as first-line therapy for RA, despite studies alluding to their superior efficacy over conventional synthetic DMARDs such as methotrexate. [Lancet 2016;388:343-355; Ther Adv Musculoskelet Dis 2017;9:249-262; Ann Rheum Dis 2017;76:1113-1136]

However, with the emergence of less expensive biosimilars, bDMARDs may become a first-line option in the future, necessitating understanding of the impact of bDMARD therapy in the first-line setting, they said.

Despite the apparent greater efficacy of the tocilizumab-methotrexate combination over tocilizumab monotherapy, the latter could be an option for patients with intolerance or contraindications to methotrexate, they added, suggesting that future research could look into the impact of these treatment strategies on drug-free remission.

“[Furthermore, the results showing that] methotrexate plus prednisone can be regarded [as] a similarly effective and safe treatment strategy is reassuring,” they added.

 

 

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Most Read Articles
Roshini Claire Anthony, 02 Feb 2018

The use of weight loss medications for at least 1 year did little to improve cardiometabolic risk factors in obese adults, according to a systematic review and meta-analysis.

17 Feb 2019
In patients with type 2 diabetes (T2D), sodium-glucose cotransporter 2 (SGLT2) inhibitor monotherapy, particularly canagliflozin, exerts greater effects on weight compared with metformin and dipeptidyl peptidase 4 (DPP-4) inhibitors or gliptins, according to the results of a meta-analysis.
26 Feb 2019
Oral fluoxetine confers beneficial effects in the management of adult and adolescent amblyopia, suggests a recent study.
19 Feb 2019
Preprandial administration of metformin successfully and safely reduces postprandial plasma triglyceride levels, a new study has shown.