RESEARCH - Rituxan (rituximab) for RA refractory to anti-TNF therapy: results of phase III trial at 24 weeks

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Arthritis Rheum. 2006 Sep;54(9):2793-806.

Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor

therapy: Results of a multicenter, randomized, double-blind,

placebo-controlled, phase III trial evaluating primary efficacy and safety

at twenty-four weeks.

Radiant Research, Dallas, Texas.

OBJECTIVE: To determine the efficacy and safety of treatment with rituximab

plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA)

who had an inadequate response to anti-tumor necrosis factor (anti-TNF)

therapies and to explore the pharmacokinetics and pharmacodynamics of

rituximab in this population. METHODS: We evaluated primary efficacy and

safety at 24 weeks in patients enrolled in the Randomized Evaluation of

Long-Term Efficacy of Rituximab in RA (REFLEX) Trial, a 2-year, multicenter,

randomized, double-blind, placebo-controlled, phase III study of rituximab

therapy. Patients with active RA and an inadequate response to 1 or more

anti-TNF agents were randomized to receive intravenous rituximab (1 course,

consisting of 2 infusions of 1,000 mg each) or placebo, both with background

MTX. The primary efficacy end point was a response on the American College

of Rheumatology 20% improvement criteria (ACR20) at 24 weeks. Secondary end

points were responses on the ACR50 and ACR70 improvement criteria, the

Disease Activity Score in 28 joints, and the European League against

Rheumatism (EULAR) response criteria at 24 weeks. Additional end points

included scores on the Functional Assessment of Chronic Illness

Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire (HAQ) Disability

Index (DI), and Short Form 36 (SF-36) instruments, as well as

Genant-modified Sharp radiographic scores at 24 weeks. RESULTS: Patients

assigned to placebo (n = 209) and rituximab (n = 311) had active,

longstanding RA. At week 24, significantly more (P < 0.0001)

rituximab-treated patients than placebo-treated patients demonstrated ACR20

(51% versus 18%), ACR50 (27% versus 5%), and ACR70 (12% versus 1%) responses

and moderate-to-good EULAR responses (65% versus 22%). All ACR response

parameters were significantly improved in rituximab-treated patients, who

also had clinically meaningful improvements in fatigue, disability, and

health-related quality of life (demonstrated by FACIT-F, HAQ DI, and SF-36

scores, respectively) and showed a trend toward less progression in

radiographic end points. Rituximab depleted peripheral CD20+ B cells, but

the mean immunoglobulin levels (IgG, IgM, and IgA) remained within normal

ranges. Most adverse events occurred with the first rituximab infusion and

were of mild-to-moderate severity. The rate of serious infections was 5.2

per 100 patient-years in the rituximab group and 3.7 per 100 patient-years

in the placebo group.

CONCLUSION: At 24 weeks, a single course of rituximab with concomitant MTX

therapy provided significant and clinically meaningful improvements in

disease activity in patients with active, longstanding RA who had an

inadequate response to 1 or more anti-TNF therapies.

PMID: 16947627

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Retrieve & dopt=Abstra\

ctPlus & list_uids=16947627

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