Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate at 1 year: The LITHE study
Kremer JL, Blanco R, Brzosko M, Burgos-Vargas R, Halland A-M, Vernon E, Ambs P, Fleischmann R. Arthritis & Rheumatism. Published online 19 November 2010. doi: 10.1002/art.30158.
The LITHE study was a 2-year double-blind, randomised, Phase III study designed to compare the efficacy and safety of tocilizumab (TCZ) in combination with methotrexate (MTX) versus MTX alone in preventing structural joint damage and improving physical function and disease activity in patients with active RA and inadequate responses to MTX. Patients were randomised to receive TCZ 8 mg/kg (n=398), 4 mg/kg (n=399) or placebo (n=393) each in combination with MTX. Year 1 results are reported.
Key study results are summarised below.
- The intent-to-treat population comprised 1,190 patients; 86% of patients completed 52 weeks, including 29% who received rescue therapy.
- More patients received rescue therapy in the control group (50%) than in the TCZ 8 mg/kg (15%) and 4 mg/kg (24%) groups.
- Progression of structural damage was reduced by 74% and 70% with TCZ 8 mg/kg or 4 mg/kg from baseline (BL) to Week 52, vs. MTX alone (p<0.0001).
- The cumulative distribution plot of change from BL in total Genant-modified Sharp score (TSS) at Week 52 showed decreased frequency and severity of progression with TCZ.
- The proportion of patients without radiographic progression (change in TSS ≤0 from BL to Week 52) was higher with TCZ (84%, 8 mg/kg; 81%, 4 mg/kg) vs. control (67%; p≤0.0001).
- Greater improvements were seen in HAQ-DI (mean AUC change from BL to Week 52) in the 8 and 4 mg/kg TCZ groups (–144.1 and –128.4 U) vs. control
(–58.1 U; p<0.0001). - Greater improvements in signs and symptoms were seen at Week 52 with TCZ 8 mg/kg + MTX vs. MTX alone:
- ACR20, 50 and 70 response rates were significantly higher and more patients achieved a major clinical response (ACR70 for 6 consecutive months) in the TCZ 8 mg/kg + MTX group.
- Decreases in DAS28 were significantly greater and proportions of patients in DAS28 remission (DAS28 <2.6) or with low disease activity (DAS ≤3.2) were significantly higher in the TCZ 8 mg/kg + MTX group.
- Adjusted mean haemoglobin levels increased from BL to Week 52 by 1.24 g/dl and 0.71 g/dl in the 8 and 4 mg/kg groups, respectively, vs. 0.13 g/dl in the control group by (p<0.0001).
- Exposure-adjusted serious adverse events were comparable across treatment groups and most adverse events were mild or moderate in severity.
In conclusion, the 1-year results show that in patients with moderate to severe RA who previously responded inadequately to MTX, the combination of TCZ + MTX results in significantly greater inhibition of progression of structural damage, improvement of physical function, and greater clinical benefits compared with MTX alone. The safety profile of TCZ was consistent with that previously reported.