COPENHAGEN, Denmark—Adding the investigational interleukin (IL)-6 receptor inhibitor tocilizumab (Actemra^®, Roche) to methotrexate is better than methotrexate alone at preventing joint destruction in rheumatoid arthritis patients, researchers announced at the 2009 European League Against Rheumatism (EULAR) Congress.

The new data is from an interim analysis of the TociLIzumab Safety and THE Prevention of Structural Joint Damage (LITHE) trial, which examined the efficacy of adding tocilizumab to methotrexate in patients with moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate.¹

1-Year interim data show only 1/3 as much joint damage progression with tocilizumab

Results at one year in about 1200 patients showed that tocilizumab-treated patients had one-third as much progression in joint damage as patients who received the treatment standard methotrexate. The study population had a mean disease duration of nine years and very active disease at baseline. Patients received stable doses of methotrexate with tocilizumab (4 mg/kg or 8 mg/kg) or placebo every four weeks and could receive blinded rescue therapy starting at week 16.

One-year data revealed that patients assigned to either the 8 mg/kg or 4 mg/kg dose of tocilizumab had significant inhibition in the progression of structural joint damage documented by the change in the mean Genant-modified Total Sharp Score (GmTSS) versus patients assigned to methotrexate plus placebo (0.29, 0.34, and 1.3, respectively, p< 0.001).

A complete lack of GmTSS progression was shown in 85%, 81%, and 67% of the three groups, respectively, p≤ 0.0001.

“Inhibiting structural joint damage in rheumatoid arthritis patients is a critical measure of a drug’s efficacy,” principal investigator Joel Kremer, MD, Director of Research at the Center for Rheumatology in Albany, New York, said. “What we saw was virtually no progression. In other words, if two experienced radiologists were to look at the films sequentially with time, they could not tell the difference in tocilizumab-treated patients.”

RA remission rates higher with Actemra

Rates of disease remission were also superior with the IL-6 inhibitor, with higher percentages of patients in both tocilizumab arms achieving disease remission confirmed by a disease activity score DAS28 less than 2.6 (47%, 30%, and 8% for the three groups, respectively).

“More than two-thirds of rheumatoid arthritis patients have radiographic evidence of joint damage within two years with local destruction of the articular bone and cartilage leading to significant disability,” said Rieke H. E. Alten, MD, chief of the internal medicine division at Schlosspark Clinic in Berlin.  

“The findings are important because if you can demonstrate that the destruction is no longer ‘ongoing,’ then you can preserve by physiotherapy and occupational therapy the normal function of the hands and all the other joints,” Dr. Alten said. “And that’s a prerequisite for keeping patients as they were before the disease struck them.”

Second study shows tocilizumab efficacy extends for over 2 years

Elsewhere at the meeting, Josef Smolen, MD, chairman of rheumatology department at the Medical University of Vienna, reported that initial beneficial results with tocilizumab in rheumatoid arthritis patients are maintained when treatment is extended up to 132 weeks.²

Efficacy endured over time in ACR response rates, DAS28 scores, and EULAR good response rates in patients on tocilizumab monotherapy, in patients who had responded inadequately to anti-TNF drugs (anti-TNF-IR), and patients who had had an inadequate response to disease-modifying anti-rheumatic drugs (DMARD-IR). Importantly, the findings, from an analysis of 2,500 patients, were backed by significant improvements in ACR core components at week 96 in all three groups.

Dr. Smolen described the results of an interim analysis of two open-label, long-term extension studies that included patients who had completed one of four 24-week controlled studies of tocilizumab as monotherapy or with DMARDS. Patients were treated with tocilizumab 8 mg/kg every 4 weeks to assess the efficacy of tocilizumab for up to 2.5 years across 3 patient populations: DMARD-IR patients, anti-TNF-IR patients, and DMARD-naïve patients.

At 132 weeks, 66.7% of DMARD-IR patients had achieved an ACR50 and 43.9% had achieved an ACR70. Nineteen percent maintained an ACR70 for 24 consecutive weeks. A similar response pattern was shown in the anti-TNF-IR and monotherapy groups.

Dr. Alten commented, “It’s great to be able to offer a treatment that sustains improvements in objective measures and also allows us physicians to restore to patients the ability to perform normal activities that people tend to take for granted like holding a glass, carrying objects, and performing personal hygiene, among others.”

References

1. Kremer J, Fleischmann R, Brzezicki J, et al.  Tocilizumab inhibits structural joint damage, improves physical function, and increases DAS28 remission rates in RA patients who respond inadequately to methotrexate: the LITHE study. Presented at EULAR 2009, Copenhagen, Denmark, June 13, 2009. Presentation no. OP-0157

2. Smolen JS, Alten RHE, Gomez-Reino J, et al. Efficacy of tocilizumab (TCZ) in rheumatoid arthritis (RA): Interim analysis of long-term extension trials of up to 2.5 years. Presented at: EULAR 2009, Copenhagen, June 13, 2009. Presentation no. FRI0133.