Rituximab compared with further TNF inhibitor therapy in rheumatoid arthritis patients who had previously failed TNF inhibitor therapy

Background

Results of the REFLEX study, a well-designed, randomized, placebo-controlled study by Cohen SB, et al. showed that rituximab is effective and well tolerated in patients who have had an inadequate response to one or more tumour necrosis factor inhibitors (TNF-Is).¹ At EULAR 2009, Gómez-Reino and colleagues presented the results of their prospective, observational study designed to assess the efficacy of cycling to an alternative TNF-I, compared with receiving rituximab, in patients with rheumatoid arthritis (RA) who had previously failed TNF-I therapy.²

Study desgin

• The study by Gómez-Reino and colleagues is an ongoing, multicentre, prospective, three-year observational study of a cohort of patients with RA who received either rituximab or an alternative TNF-I, having previously failed a TNF-I.
• Results are based on the first follow-up of patients at 3–6 months after treatment initiation.
• Patients were included in the study if they had active RA, which had previously been treated with a TNF-I that did not provide an adequate response, was contraindicated because of safety, or was discontinued.
• Assessments were made at baseline, on treatment adjustment, every 4 months, and on premature discontinuation, and included:
• Disease Activity Score (DAS) to evaluate inflammatory status in 28 joints (DAS28) and erythrocyte sedimentation rate (ESR);
• evaluation of 66 joints for swelling and 68 joints for tenderness;
• response assessment using European League Against Rheumatism (EULAR) criteria;
• Health Assessment Questionnaire Disability Index (HAQ-DI) score;
• patient assessment of disease activity on a Visual Analogue Scale (VAS).

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Key findings

• At the time of this analysis, there were 226 evaluable patients: 69 had received rituximab and 157 had received an alternative TNF-I.
• Compared with those receiving an alternative TNF-I, significantly more patients receiving rituximab:
• had received at least two disease-modifying anti-rheumatic drugs (DMARDs);
• reported toxicity with DMARDs;
• used concomitant glucocorticoids;
• reported morning stiffness;
• were older;
• had disease duration of >4 years;
• had higher DAS28 scores, swollen joint count (SJC), tender joint count (TJC), ESR, and HAQ-DI scores.
• The number of patients who were rheumatoid factor (RF) positive at baseline in each group was not given.
• In the first 3–6 months, rituximab-treated patients had a greater mean change in DAS28 response of –1.54 (95% CI, –1.91 to –1.17) versus the TNF-I–treated patients, who had a change of –0.87 (95% CI, –1.11 to –0.64) (p = 0.002).
• A significantly greater proportion of rituximab-treated patients had a decrease in DAS28 >1.2 than those receiving an alternative TNF-I (57.6% versus 37.9%, respectively; p = 0.012).
• In a subgroup of patients with only one TNF-I failure, mean change from baseline in DAS28 was statistically significantly greater for those receiving rituximab (n = 30; mean change in DAS28 –1.6) compared with those receiving an alternative TNF-I (n = 107; mean change in DAS28 –0.8) (p = 0.008).
• There were no statistically significant differences in mean change in DAS28 between rituximab (n = 29; mean change in DAS28 –1.50) and TNF-I (n = 17; mean change in DAS28 –0. 9) treatments in a subgroup of patients with two or more previous TNF-I failures.
• Statistically significantly more rituximab-treated patients achieved a moderate or good EULAR response compared with those receiving an alternative TNF-I. (Figure 1)
• Changes from baseline in all other disease activity and patient-reported outcome measures assessed were statistically significant in favour of rituximab-treated patients over those treated with an alternative TNF-I, with the exception of HAQ-DI. (Table 1)
• Overall, both treatments were well tolerated.
• In all, 28 adverse events (AEs) were reported (15 in the rituximab group and 13 in the TNF-I group), with some patients experiencing more than one AE.
• A total of 8 infections were reported: 3 infections in the rituximab group and 5 in the TNF-I group.

Key conclusions

• Rituximab provides an alternative therapeutic option to TNF cycling in RA patients who have failed previous TNF inhibitor therapy.

References: 1. Cohen SB, Emery P, Greenwald MW, et al. Rituximab for rheumatoid arthritis refractory to anti-tumour necrosis factor therapy: results of a multi-center, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006;54:2793–2806. 2. Gómez-Reino JJ, Sanmarti R, Azpeitia D, et al. Rituximab compared with further tumour necrosis factor antagonist therapy in rheumatoid arthritis patients who had previously failed TNF antagonist therapy. Program and abstracts of the 2009 European League Against Rheumatism (EULAR) Scientific Meeting, June 10–13, 2009, Copenhagen, Denmark: Abstract FRI0257.