FRI0202 RETREATMENT WITH RITUXIMAB BASED ON A TREATMENT TO TARGET APPROACH PROVIDES BETTER DISEASE CONTROL THAN TREATMENT AS NEEDED IN PATIENTS WITH RA
P. Emery 1,*P. J. Mease 2A. Rubbert-Roth 3J. R. Curtis 4U. Müller-Ladner 5N. Gaylis 6S. Williams 7H. Tyrell 7M. Reynard 7
1Academic Unit of Musculoskeletal Disease, Leeds University, Leeds, United Kingdom, 2Rheumatology, Seattle Rheum Assoc, Seattle, United States, 3Med Clinic I, University of Cologne, Cologne, Germany, 4Rheumatology, University of Alabama, Birmingham, United States, 5Rheumatology and Clinical Immunology, Kerckhoff Clinic, Bad Nauheim, Germany, 6Rheumatology, Arthritis and Rheumatic Disease Specialties, Aventura, United States, 7Roche Products Ltd, Welwyn Garden City, United Kingdom
Background: Two retreatment strategies have been employed in clinical trials of rituximab (RTX) in RA. Assessing differences in efficacy and safety profiles may be useful in determining an optimal treatment regimen.
Methods: RA patients (pts) with an inadequate response to methotrexate (MTX) recruited into Phase II or III studies received open-label RTX 2 x 1000mg, IV 2 weeks apart + MTX based on 2 approaches: a) Treatment to target (TT): pts were assessed 24 wks after each course and were retreated if and when not in remission (DAS28 ≥2.6); b) Treatment as needed (PRN): pts were retreated at the physician’s discretion after ≥16 wks if both swollen and tender joint counts were ≥8. Regardless of treatment strategy, study visits were at least every 8 wks. Data were pooled across trials (MIRROR1, SERENE2, Phase IIa3 and DANCER4) and analysed according to treatment strategy. Clinical outcomes including ACRn, DAS28-ESR and HAQ-DI responses and safety data were evaluated over time.
Results: Over multiple courses of RTX, and compared with baseline, responses were maintained or improved in both treatment groups. However, compared with PRN, TT provided tighter control of disease activity as indicated by greater improvements in DAS28-ESR (Figure), lower HAQ-DI and higher ACRn. PRN resulted in recurrence of disease symptoms between courses as evidenced by DAS28-ESR scores returning close to pre-RTX treatment levels, together with higher rates of withdrawals from the trial due to RA flare. TT also resulted in more pts achieving major clinical response (ACR70 ≥6 months) compared with PRN (12.3% vs 5.1%). TT resulted in more frequent retreatment with a median time between courses of approx 25 wks compared with approx 62 wks for PRN. Importantly, the safety profiles of the regimens were comparable. Also of note, in comparison with PRN, TT had a numerically reduced rate of serious infections (2.2 vs 3.5 per 100 pt-yrs) and serious adverse events (12.0 vs 16.2 per 100 pt-yrs). There were no clinically relevant differences at any time in the proportion of pts with Ig levels below the lower limit of normal across the two treatment groups.
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Conclusion: Repeat treatment to a target of DAS28 remission with RTX led to tighter control of disease activity compared with PRN treatment.
References: 1. Rubbert-Roth A, et al. Arth Rheum 2008;58:Suppl:S301.
2. Emery P, et al. Arth Rheum 2008;58:Suppl:S302.
3. Edwards J, et al. NEJM 2004;350:2572–81.
4. Emery P, et al. Arth Rheum 2006;54:1390–1400.
Disclosure of Interest: P. Emery Grant / Research Support from: Roche, Abbott Consultant for: Roche, Pfizer, Merck, Abbott, BMSP. Mease: None DeclaredA. Rubbert-Roth Consultant for: Roche, Wyeth, Abbott, UCB, Essex, BMS, Chugai Speakers Bureau: RocheJ. Curtis Grant / Research Support from: Novartis, Amgen, Merck, Procter & Gamble, Eli Lilly, Roche, Centocor, CORRONA Consultant for: Roche, UCB, Procter & Gamble, Amgen, Centocor, CORRONA Speakers Bureau: Novartis, Procter & Gamble, Eli Lilly, Roche, MerckU. Müller-Ladner Grant / Research Support from: German Research Foundation Consultant for: Abbott, Wyeth, UCB, Roche, Chugai, Essex, Medac, MSD, MerckN. Gaylis Grant / Research Support from: Abbott, BMS, Centocor, Eli Lilly, Human Genome Sciences, Pfizer, Rigel, Roche/ Genentech, UCB Consultant for: Centocor Speakers Bureau: Centocor, Roche/GenentechS. Williams: None DeclaredH. Tyrell: None DeclaredM. Reynard: None Declared