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Initiating tocilizumab, with or without methotrexate, compared with starting methotrexate with prednisone within step-up treatment strategies in early rheumatoid arthritis: an indirect comparison of effectiveness and safety of the U-Act-Early and CAMERA-II treat-to-target trials
  1. Maxime MA Verhoeven1,
  2. Marjolein JH de Hair1,
  3. Janneke Tekstra1,
  4. Johannes WJ Bijlsma1,
  5. Jacob M van Laar1,
  6. Attila Pethoe-Schramm2,
  7. Michelle EA Borm3,
  8. Evert-Jan ter Borg4,
  9. Suzanne P Linn-Rasker5,
  10. Xavier M Teitsma1,
  11. Floris PJG Lafeber1,
  12. Johannes WG Jacobs1,
  13. Paco MJ Welsing1
  1. 1 Rheumatology and Clinical Immunology, UMC Utrecht, Utrecht, The Netherlands
  2. 2 ACTEMRA/Rheumatology, F Hoffmann-La Roche AG, Basel, Switzerland
  3. 3 Rheumatology, Roche Nederland BV, Woerden, The Netherlands
  4. 4 Department of Rheumatology, Sint Antonius Ziekenhuis, Nieuwegein, The Netherlands
  5. 5 Department of Rheumatology, Meander Medical Centre, Amersfoort, The Netherlands
  1. Correspondence to Maxime MA Verhoeven, Rheumatology & Clinical Immunology, UMC Utrecht, Utrecht 3508 GA, The Netherlands; m.m.a.verhoeven-15{at}


Objectives Methotrexate (MTX), often combined with low moderately dosed prednisone, is still the cornerstone of initial treatment for early rheumatoid arthritis (RA). It is not known how this strategy compares with initial treatment with a biological. We therefore compared the effectiveness of tocilizumab (TCZ), or TCZ plus MTX (TCZ+MTX) with MTX plus 10 mg prednisone (MTX+pred), all initiated within a treat-to-target treatment strategy in early RA.

Methods Using individual patient data of two trials, we indirectly compared tight-controlled treat-to-target strategies initiating TCZ (n=103), TCZ+MTX (n=106) or MTX+pred (n=117), using initiation of MTX (n=227) as reference. Primary outcome was Disease Activity Score assessing 28 joints (DAS28) over 24 months. To assess the influence of acute phase reactants (APRs), a disease activity composite outcome score without APR (ie, modification of the Clinical Disease Activity Index (m-CDAI)) was analysed. Secondary outcomes were remission (several definitions), physical function and radiographic progression. Multilevel models were used to account for clustering within trials and patients over time, correcting for relevant confounders.

Results DAS28 over 24 months was lower for TCZ+MTX than for MTX+Pred (mean difference: −0.62 (95% CI −1.14 to −0.10)). Remission was more often achieved in TCZ+MTX and in TCZ versus MTX+pred (p=0.02/0.05, respectively). Excluding APRs from the disease activity outcome score, TCZ-based strategies showed a slightly higher m-CDAI compared with MTX+pred, but this was not statistically significant. Other outcomes were also not statistically significantly different between the strategies.

Conclusions In patients with early RA, although TCZ-based strategies resulted in better DAS28 and remission rates compared with MTX+pred, at least part of these effects may be due to a specific effect of TCZ on APRs.

  • early rheumatoid arthritis
  • treat-to-target
  • glucocorticoids
  • tocilizumab
  • methotrexate

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  • Handling editor Josef S Smolen

  • Contributors PMJW, MMAV and MJHdH contributed to study design, data cleaning and data analysis. All authors contributed to data interpretation, writing of the report, revising it critically and approved the final version to be published and agree to be accountable for all aspects.

  • Funding The U-Act-Early trial was funded by Roche Nederland BV, and the CAMERA-II trial was financially supported by the Catharijne Foundation (grant 20063).

  • Competing interests JWJB reports grants and fees from Roche, AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer and UCB. JMvL reports grants from Arthrogen, grants from MSD, personal fees from Pfizer, personal fees from Eli Lilly, personal fees from BMS, grants from Astra Zeneca and grants from Roche-Genentech. AP-S is an employee of F Hoffmann-La Roche. MEAB is an employee of Roche Netherlands BV. FPJL reports grants from Roche.

  • Patient consent for publication Not required.

  • Ethics approval The medical ethics research committee of the University Medical Center Utrecht approved both studies (U-Act-Early and CAMERA-II) with subsequent sanctioning of all participating hospitals. Study ID number: ML28388 and NHMRC1078930.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No data are available.