Background Initial reports of biologic therapy (mainly TNF-inhibitor) following B-cell depletion suggest this to be safe and effective 1. Disease which has been refractory to B cell depletion therapy may respond differently to co-stimulation or cytokine (IL-6) blockade. Histological evidence suggests significant reduction in CD20+ cells in Abatacept responder group2.
Objectives To evaluate safety and efficacy of either T-cell co-stimulation blockade therapy or anti-cytokine (IL-6 receptor) treatment following B-cell depletion in patients with RA.
Methods Patients with RA who have received abatacept (ABT) or tocilizumab (TCZ) following rituximab (RTX) therapy were identified from our single-centre biologics database. Preliminary data on disease activity is reported with patient reported outcome analysis also planned.
Results 51 patients [40 (78.4%) female, 11 (21.6%) male] have received either ABT (16) or TCZ (35); mean (SEM) age of 58.1 years (2.31) with median (range) disease duration of 12 years (4-56). All patients were positive for either rheumatoid factor (RF) (n=47, 92.2%) or CCP antibodies (CCP) (n=44, 86.3%), 48/51 (94.1%) had erosive disease. All patients had failed at least 2 DMARDs and 1 TNF-inhibitor (46.3% secondary non-responders) and had received at least 1 cycle of rituximab (maximum of 4); of the 51, 21 (41.2%) were RTX primary non-responders, 20 (39.2%) secondary non-responders and 10 (19.6%) had side-effects. 39/51 (76.4%) were on concomitant DMARD [33 methotrexate (MTX)].
Mean (SEM) DAS28 (ESR) score across the group was 5.76 (0.17), tender joint count (TJC) 13.96 (1.1), swollen joint (SJC) 5.88 (0.55) CRP 25.1 (5.6) and VAS GH 70.84 (2.4).
The median (range) interval with first dose of abatacept or tocilizumab following rituximab was 43 weeks (0-208) (partly due to requirement for funding approval).
In the ABT group: mean (SEM) SJC and CRP changed from 6.5 (1.1) and 16.3 (7.0) to 4.15 (1.2) and 19.9 (8.2) respectively. In the TCZ group: mean (SEM) SJC and CRP changed from 5.59 (0.63) and 29.4 (7.6) to 2.70 (0.6; p<0.001)) and 3.1 (1.5: p<0.001) respectively. Table 1 details DAS28 score and EULAR response at 6 months for the ABT and TCZ groups.
The main reason for discontinuation in both groups was toxicity (ABT-37% and TCZ-14.3%).
Conclusions This preliminary observational report suggests abatacept and tocilizumab were effective and tolerated in patients who had previously failed rituximab. Tocilizumab seemed to have a better response. Vigilance with such successive biologic therapy should be maintained as the main reason for discontinuation of therapy was side effects across both groups.
Genovese MC, Ann Rheum Dis 2009 Dec;68(12):1894-7
MH Buch, Ann Rheum Dis 2009;68:1220-1227
Disclosure of Interest S. Das: None Declared, S. Horton: None Declared, E. Vital Grant/Research support from: Honararium from Roche, D. Bryer: None Declared, P. Emery Grant/Research support from: Bristol-Myers Squibb, Pfizer,Roche, Consultant for: Abbott, Roche, Bristol-Myers Squibb, Pfizer, Speakers Bureau: Roche, Bristol-Myers Squibb, Pfizer, M. Buch Grant/Research support from: Bristol-Myers Squibb, Pfizer, Consultant for: Abbott,Roche, Bristol-Myers Squibb, Speakers Bureau: Roche
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