EULAR 2009: Tocilizumab Prevents Joint Damage, Improves Physical Function in Rheumatoid Arthritis

Alice Goodman

June 17, 2009

June 17, 2009 (Copenhagen, Denmark) — Tocilizumab plus methotrexate inhibited the progression of structural joint damage and improved physical function and clinical disease activity, compared with methotrexate alone, in patients with rheumatoid arthritis in a preplanned 1-year analysis of the LITHE study reported here at EULAR 2009: The Annual European Congress of Rheumatology.

"The benefits of tocilizumab [plus methotrexate] shown in this study are meaningful to patients, while at the same time helping them maintain day-to-day function," said Joel Kremer, MD, director of research at The Center for Rheumatology in Albany, New York. "Tocilizumab was effective even in patients with a relatively long disease duration, suggesting that it may be an effective treatment option for many patients with rheumatoid arthritis."

Tocilizumab is a novel interleukin-6 receptor inhibitor, and — like tumor-necrosis-factor-alpha blockers — the drug inhibits mediators of inflammation.

The multinational double-blind randomized controlled 3-group trial enrolled more than 1200 patients at 137 sites in 15 countries (1190 were evaluable in an intention-to-treat analysis at 1 year). All patients had moderate to severe rheumatoid arthritis with an inadequate response to methotrexate monotherapy. Patients were randomized to receive stable doses of methotrexate plus tocilizumab 4 mg/kg, tocilizumab 8 mg/kg, or placebo every 4 weeks. Blinded rescue therapy was allowed beginning at week 16.

At all time points for all end points, the 8 mg/kg dose of tocilizumab was numerically superior to the 4 mg/kg dose. At 1 year, the percentage of patients in remission according to Disease Activity Score (DAS28) was 47.2% for the 8 mg/kg dose, 30.2% for the 4 mg/kg dose, and 7.9% for placebo (P ≤ .0001 for both doses vs placebo in evaluable patients).

"DAS28 remission increased from week 24 to 52, indicating an increasing magnitude of clinical benefit over time," Dr. Kremer commented.

Patients treated with either dose of tocilizumab plus methotrexate exhibited significant inhibition of progression of structural joint damage, compared with placebo, as measured by change in the mean Genant-modified Sharp score (0.29 for 8 mg/kg and 0.34 for 4 mg/kg vs 1.1 for placebo; P  .001).

Significantly more patients treated with either dose of tocilizumab than with placebo experienced no progression of structural joint damage from baseline (81% for 8 mg/kg and 85% for 4 mg/kg vs 67% for placebo; ≤ .0001). Most patients also experienced improved physical function after treatment with tocilizumab, as assessed by the Health Assessment Questionnaire-Disability Index.

Treatment with tocilizumab achieved a reduction in signs and symptoms of rheumatoid arthritis, compared with placebo, as shown by American College of Rheumatology scores showing 20%, 50%, and 70% improvement (ACR20, ACR50, and ACR70 responses, respectively).

Table. Efficacy According to ACR20, ACR50, and ACR70 Response

Efficacy at Week 52 Tocilizumab 8 mg/kg + Methotrexate, n = 398 Tocilizumab 4 mg/kg + Methotrexate, n = 399 Placebo + Methotrexate, n = 393
ACR20 (n) 56% (222)* 47% (186)* 25% (97)
ACR50 (n) 36% (145)* 29% (116)* 10% (39)
ACR70 (n) 20% (80)* 16% (65)* 4% (15)
*P < .0001 vs control

Preliminary Data Exciting

"We can intervene at multiple pathways involved in development of inflamed swollen joints and see an effect. The dream is to get nearer to the initiating event in rheumatoid arthritis, which is still unknown," said Andrew Cope, MD, professor at King's College in London, United Kingdom.

Until that initiating event is identified, rheumatologists have a large armamentarium of drugs for rheumatoid arthritis. Dr. Cope concluded that "the data on tocilizumab are exciting and the long-term results look good thus far. We need more long-term data on efficacy, safety, and effects on radiography. So far, it appears the drug works relatively quickly and the safety signals are good."

The study was funded by Roche. Dr. Cope has disclosed no relevant financial relationships.

EULAR 2009: The Annual European Congress of Rheumatology: Abstract OP-0157. Presented June 11, 2009.

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