RA TNF Antagonists
Abstract 2123: One-Year Results of Golimumab Compared With Placebo in Patients With Active RA Despite Treatment With Methotrexate: A Phase II, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial
AUTHORS: J Kay, EL Matteson, B Dasgupta, P Nash, P Durez, S Hall, EC Hsia, P Chiruvolu, J Han, MU Rahman.
BACKGROUND: TNF inhibition has proven to be an effective strategy for the treatment of RA, PsA, AS, and other inflammatory diseases. Several additional TNF antagonists are in development. Golimumab (GLB) (previously known as CNTO 148), is a human monoclonal antibody to TNFα with higher affinity for TNFα and neutralizing ability than other anti-TNF monoclonal antibodies.
METHODS: This was a multicenter trial in 172 patients with RA refractory to MTX randomized to placebo (PBO); GLB 50 mg q4 wks; GLB 50 mg q2 wks; GLB 100 mg q4 wks; or GLB 100 mg q2 wks. The trial was double-blinded and placebo-controlled from wks 0 to 20. At wk 20, patients in the placebo group received open-label infliximab (3 mg/kg) through wk 44. Other groups received GLB at assigned dose (50 or 100 mg) through wk 20, then all were switched/maintained at q4 wks through wk 48. All pts received stable doses of MTX (>10 mg/wk). The primary endpoint was ACR 20 response at wk 16.
RESULTS: The clinical characteristics of the patients were not presented in the abstract. ACR and EULAR responses were achieved at 16 weeks and increased through week 52 even in patients who had their frequency of infusion decreased from every 2 weeks to every 4 weeks.
Table: ACR and DAS 28 assessments
Assessment |
Placebo | 50 mg q4 wks+ MTX | 50 mg q2 wks+ MTX++ | 100 mg q4 wks+ MTX | 100 mg q2 wks+ MTX++ |
| ACR 20 | |||||
| N | 35 | 35 | 34 | 34 | 34 |
| Wk 16 | 13 (37.1%) | 22 (62.9%)* | 17 (50.0%) | 19 (55.9%) | 27 (79.4%)* |
| N | -- | 28 | 24 | 26 | 29 |
| Wk 52 | -- | 21 (75%) | 15 (62.5%) | 19 (73.1%) | 24 (80.8%) |
| ACR 50 | |||||
| Wk 16 |
2 (5.7%) |
14 (40.0%)* | 8 (23.5%)* | 10 (29.4%)* | 11 (32.4%)* |
| Wk 52 | -- | 14 (50%) | 9 (37.5%) | 12 (46.2%) | 13 (44.8%) |
| ACR 70 | |||||
| Wk 16 |
0 (0.0%) |
3 (8.6%) | 5 (14.7%)* | 6 (17.6%)* | 3 (8.8%) |
| Wk 52 | -- | 7 (25%) | 5 (20.8%) | 7 (26.9%) | 4 (13.8%) |
| DAS 28 good/moderate responders | |||||
| Wk 16 | 19 (54.3%) | 27 (77.1%) | 22 (64.7%) | 23 (67.6%) | 29 (85.3%) |
| Wk 52 | -- | 26 (92.9%) | 19 (79.2%) | 23 (88.5%) | 25 (89.3%) |
| * p < 0.05 compared to placebo; ++switched to every 4 weeks after week 20 | |||||
Serious adverse events (SAEs) prior to crossover through week 20 were 8% for the GLB groups combined vs 5.9% for the PBO group. SAEs after crossover from week 20 to week 52 were 12% for the infliximab group and 9.2% for the combined GLB groups. The most common clinically relevant SAEs through wk 52 in GLB-treated pts were pneumonia (3 pts), lung cancer (unrelated, 1 pt), cardiac tamponade (1 pt), and cardiac failure (1 pt). There were no deaths, TB, or lymphoma through wk 52. One GLB patient died from coronary artery disease approximately 4 months after completing 52 wks of the study.
CONCLUSION: Golimumab was effective in the reduction in signs and symptoms of RA. These responses were significant at 16 weeks and continued to increase through week 52.
EDITORIAL COMMENT:
The results presented here for Golimumab are very much in line with the responses seen with other TNF antagonists currently available. Interpreting these results would be aided with a better description of the baseline characteristics of the patients however. It is interesting that the patients who received equivalent aggregate doses of drug (50 mg every 2 weeks versus 100 mg every 4 weeks) seemed to respond better when dosed on the every 4 week regimen. At the highest dose studied (100mg every 2 weeks) there was not a substantial benefit or further improvement indicating a potential ceiling effect for the drug. The adverse events reported are in line with other agents of the class. Beyond the possibility of more convenient monthly SQ dosing, it is unclear that the drug will offer a unique efficacy or safety advantage to existing products.
