Tocilizumab With and Without Methotrexate for Preventing Radiographic Progression in RA

Although the combination of tocilizumab with methotrexate is more effective than tocilizumab alone for the prevention of radiographic progression in patients with rheumatoid arthritis (RA), in early RA with more joint damage or lower disease activity, the effectiveness of both regimens may be equivalent, according to study results published in Arthritis Care & Research.

Methotrexate is a common first-line disease-modifying antirheumatic drug in RA, whereas tocilizumab may be used in patients intolerant to methotrexate due to side effects, aversion, or inadequate efficacy.  The objective of the current study was to determine the efficacy of tocilizumab as monotherapy or in combination with methotrexate for the prevention of radiographic progression in patients with RA.

Using individual patient data from randomized trials, the effect of preventing radiographic progression of tocilizumab monotherapy was compared to the effect of tocilizumab with methotrexate.  Preventing radiographic progression was the main study outcome and was defined as no evidence of radiographic progression after 2 years in total Sharp van der Heijde (SvdH) score, in erosion score, and in joint space narrowing score.

The 2 tocilizumab regimens that were compared consisted of (1) intravenous tocilizumab 8 mg/kg every 4 weeks with methotrexate median weekly dose of 15 mg and (2) intravenous tocilizumab 8 mg/kg every 4 weeks.

The study sample included data on 1506 patients, including 1089 subjects (838 women, mean age 50.8 years) with early RA and 417 patients (345 women, mean age 52.8 years) with established RA.

In general, the combination of tocilizumab with methotrexate was better than tocilizumab monotherapy for the prevention of radiographic progression. However, the effectiveness of tocilizumab monotherapy was similar to that of combination treatment for early RA patients with lower disease activity score or more joint damage at baseline.

In patients with early RA, tocilizumab monotherapy resulted in less prevention of radiographic progression according to total SvdH scores than combination therapy (relative risk [RR], 0.96; 95% CI, 0.90-1.03). However, the advantage of tocilizumab with methotrexate over tocilizumab monotherapy disappeared with more joint damage (RR for preventing the progression of 1.02 [95% CI, 0.87-1.18] with monotherapy vs. 0.91 [95% CI, 0.81-1.02] with combination treatment) or with lower disease activity score (RR, 1.04 [0.93-1.17] vs. RR, 0.92 [0.83-1.03], respectively).

The absolute risk difference between tocilizumab monotherapy vs tocilizumab with methotrexate was 8% in patients with low-level baseline joint damage vs only 1% with high-level baseline joint damage. Outcomes for erosions were partly in line with those of total SvdH score, whereas the outcomes were less clear regarding joint space narrowing.

In patients with established RA, the combination of tocilizumab with methotrexate was more effective in preventing radiographic progression regarding total SvdH, compared with tocilizumab monotherapy (relative risk, 0.96; 95% CI, 0.87-1.08).

However, the advantage of combination therapy over tocilizumab monotherapy on total SvdH scores disappeared with high-level baseline disease duration, as the absolute risk difference in the chance to prevent radiographic progression between treatment regimens was 10% in those with low-level baseline disease duration, compared with only 2% in those with high-level baseline disease duration.

Outcomes for erosions were in line with those of total SvdH scores (10% vs. 3%, respectively), whereas for the overall advantage of combined treatment on joint space narrowing, the results were less clear (7% vs. 0%, respectively).

The study had several limitations: Radiographs were assessed by different readers in the original trials, missing radiographic data were substantial, the sample size was relatively small, and the differences in preventing radiographic progression may not be clinically relevant in all subgroups.

“Combination therapy with TCZ [tocilizumab]+MTX [methotrexate] is more effective in preventing radiographic progression compared to TCZ-monotherapy, but the effectiveness of TCZ-monotherapy may approximate the effectiveness of TCZ+MTX in early RA patients with more joint damage and/or a lower DAS28 at baseline, and in established RA patients with longer disease duration,” concluded the researchers.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Verhoeven MMA, Tekstra J, Jacobs JWG, et al. Is tocilizumab monotherapy as effective in preventing radiographic progression in rheumatoid arthritis as its combination with methotrexate? Arthritis Care Res. Published online Nov 30, 2020. Arthritis Care Res. doi:10.1002/acr.24524