Efficacy of Tocilizumab Monotherapy in Methotrexate-Naïve RA

Long-term efficacy and safety data indicated tocilizumab monotherapy as an option for patients who do not tolerate methotrexate.

A long-term extension of the AMBITION study has demonstrated continued efficacy and safety of tocilizumab (TCZ), indicating a sustained effect without methotrexate (MTX) therapy, according to research published in the Journal of Rheuamtology.

Graeme Jones, MBBS, FRACP, MD, professor at the Menzies Research Institute at the University of Tasmania in Australia, and colleagues, reported on the 5-year efficacy and safety results of the AMBITION study (ClinicalTrials.gov identifiers NCT00109408 and NCT00720798).

High Yield Data Summary

  • Tocilizumab monotherapy is safe and efficacious in patients for whom methotrexate therapy is not an option.

In the 24-week, randomized controlled AMBITION trial, researchers assessed the efficacy and safety of TCZ monotherapy in patients with active rheumatoid arthritis (RA) who were either MTX-naïve or MTX-free for 6 months. Patients received either TCZ 8 mg/kg intravenously every 4 weeks or oral MTX weekly (7.5 mg, escalating to 20 mg). 

Patients enrolled in the placebo-controlled sub-study received placebo oral MTX and placebo intravenous infusions at weeks 0, 4, and 8, followed by TCZ 8 mg/kg for 16 weeks, with the option to enroll in a long-term extension study at 24 weeks.

The objective of the long-term extension study was to determine the efficacy and safety of TCZ-treated patients from first dose through 264 weeks; follow-up safety assessments were continued for up to 276 weeks.

Assessments of efficacy included Disease Activity Score at 28 joints (DAS28), American College of Rheumatology (ACR) 20/50/70 responses, the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI).

A total of 286 patients received TCZ 8 mg/kg monotherapy as part of the AMBITION core study; 243 patients continued participation in the long-term extension study. Of those patients, 55% continued with monotherapy, while 45% added a disease-modifying anti-rheumatic drug (DMARD). At the conclusion of the long-term extension period, 70.1% of patients remained in the study—in other words, 39% of patients initially assigned to receive TCZ monotherapy completed 5 years of TCZ monotherapy treatment, with 14% and 15.7% withdrawing for safety and non-safety (treatment refusal, consent withdrawal, insufficient therapeutic response) reasons, respectively.

Time to maximum response (DAS28 < 2.6, SDAI ≤ 3.3, or CDAI ≤ 2.8) was approximately 130 weeks, maintained through week 264. At weeks 24 and 264, 40.2% and 65.2% of patients achieved DAS28 clinical remission; 85.8%, 56.7%, and 35.8% of patients achieved ACR 20/50/70 response at 24 weeks, whereas 90.5%, 77.9%, and 60% of patients achieved response at 264 weeks. CDAI and SDAI remission rates were 16.5% and 20.3% at week 24 and 43% and 46.2% at 264 weeks, indicating that TCZ monotherapy was durable and had increasing efficacy over time.

Over 100 patient-years, the rate of severe adverse events was 14.96 (95% confidence interval [CI], 12.16 to 18.22); the most common severe adverse event was infection, the most common of which was pneumonia. Overall serious infection event rate was 5.74 (95% CI, 4.06 to 7.88) per 100 patient-years. Two occurrences of myocardial infarction in 2 patients and 8 occurrences of stroke in 7 patients were reported at 276 weeks (1.21 [95% CI, 0.52 to 2.38] per 100 person-years). However, no “obvious associations” between severe adverse events and duration of TCZ exposure were noted by the researchers.

Summary and Clinical Applicability

“Results of the 5-year [long-term extension] study of AMBITION confirm the continued efficacy and safety of TCZ as monotherapy that has been demonstrated previously,” Dr Jones and colleagues noted, indicating that patients’ risk for serious infections remained stable throughout the course of the AMBITION long-term extension.

Safe, long-term treatment of patients with RA using TCZ monotherapy is important for patients who are unable to tolerate MTX. 


  • Long-term extension studies typically include a population of patients who have responded well to treatment and who do not experience tolerability issues.
  • Efficacy results in the current study show nonresponder imputation, as well as observed data, to minimize bias associated with long-term extensions.


Dr Sebba reports receiving research and consulting fees from Jansen and Jansen, Novartis, Genentech, Pfizer, Lilly, Amgen, Sandoz, and Sanofi. Dr Wallace is an employee of and owns stock options in Genentech. Dr McIntosh is an employee of Genentech. Dr Brockwell is an employee of Roche Products Ltd.

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Jones G, Wallace T, McIntosh MJ, et al. Five-year efficacy and safety of tocilizumab monotherapy in patients with rheumatoid arthritis who were methotrexate- and biologic-naïve or free of methotrexate for 6 months: the AMBITION study. J Rheum. 2016 Dec 1. doi:10.3899/jrheum.160287 [Epub ahead of print] 

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