A randomised comparative study of the short term clinical and biological effects of intravenous pulse methylprednisolone and infliximab in patients with active rheumatoid arthritis despite methotrexate treatment

Abstract

Objectives: To compare the short term clinical and biological effects of intravenous (i.v.) pulse methylprednisolone (MP) and infliximab (IFX) in patients with severe active rheumatoid arthritis (RA) despite methotrexate (MTX) treatment.

Methods: Patients with active RA despite MTX treatment were randomly allocated to receive a single i.v. infusion of MP (1 g) or three i.v. infusions of IFX (3 mg/kg) on weeks 0, 2, and 6. Patients were "blindly" evaluated for disease activity measures. Quality of life (QoL) was evaluated through the SF-36 health survey. Serum matrix metalloproteinase-3 (MMP-3) titres were measured at baseline, weeks 2 and 6.

Results: Compared with baseline, significant improvement was noted in all activity measures, including serum C reactive protein (CRP) titres, in the IFX group only. At week 14, 6/9 (67%) and 4/9 (44%) IFX patients met the ACR20 and 50 response criteria, while this was the case in only 1/12 (8%) and 0/12 (0%) MP patients, respectively (p<0.05). None of the QoL scales improved with MP treatment, whereas some did so in the IFX group. Serum MMP-3 titres significantly decreased (41% drop) at week 6 in the IFX group, while no changes were seen in patients given MP.

Conclusion: This short term randomised comparative study demonstrates that TNF blockade is better than MP pulse therapy in a subset of patients with severe refractory RA, with improvement in not only clinical parameters of disease activity but also biological inflammatory indices, such as serum CRP and MMP-3 titres.

Figure 1

Disease activity measures in patients treated with MP pulse (circles) or IFX (squares). Results are presented as means (SEM). Asterisks placed below the squares refer to between-groups p values. Asterisks placed above the squares or the circles refer to intragroup p values. *p<0.05; **p<0.005; ***p<0.0005.

Figure 2

American College of Rheumatology (ACR) 20 and 50 response rates at week 14 in patients treated with IFX or MP. Owing to missing TJC values, the ACR response rates could be calculated for only 12 and 9 patients from the MP and IFX group, respectively.

Figure 3

Serum IL6 and MMP-3 titres measured in patients treated with IFX or MP. Results are means (SEM). Significant between-groups and intragroup differences are indicated by corresponding p values.

Figure 4

Disease activity measures in patients randomised to the MP group and given open access to IFX treatment, immediately before and 2 weeks after the first IFX injection. Results are means (SEM). Significant differences are indicated by corresponding p values.