OP0048 RATE OF SERIOUS INFECTIONS IN RA PATIENTS WHO SUBSEQUENTLY RECEIVE OTHER BIOLOGIC THERAPIES AFTER DISCONTINUING RITUXIMAB TREATMENT

M. Genovese ^1,*F. Breedveld ²P. Emery ³S. Cohen ⁴E. Keystone ⁵E. Matteson ⁶L. Burke ⁷A. Chai ⁸W. Reiss ⁸M. Sweetser ⁹T. Shaw ⁷

¹Stanford University, Palo Alto, United States, ²Leiden University, Leiden, Netherlands, ³Leeds University, Leeds, United Kingdom, ⁴Metroplex Clinical Research Center, Dallas, United States, ⁵University of Toronto, Toronto, Canada, ⁶Mayo Clinic, Rochester, United States, ⁷Roche, Welwyn Garden City, United Kingdom, ⁸Genentech, South San Francisco, ⁹Biogen Idec, Cambridge, United States

Background: Rituximab (RTX) selectively targets CD20+ B-cells and is an approved biologic in the treatment of RA patients (pts) who have had an inadequate response to ≥1 TNF-inhibitor(s) (TNFi). The pharmacodynamic effect of RTX may be long lasting. The safety of treatment with other biologic disease-modifying antirheumatic drugs (BDMARDs) is an important clinical question during this period of peripheral B-cell depletion in pts who have discontinued RTX.

Objectives: To describe the rate of serious infection events (SIEs) in RA pts treated with RTX and who subsequently received a BDMARD while potentially peripherally B-cell depleted.

Methods: Pts with moderately-to-severely active RA who received RTX+methotrexate within an international clinical trial program were included. Following completion or withdrawal from their studies, pts entered safety follow-up (SFU) and peripheral B-cell counts were monitored at regular intervals for ≥48 wks. During SFU, pts were permitted to receive BDMARDs. All SIEs, defined as serious adverse events and/or infections that required IV antibiotics, were collected.

Results: As of Sept 2009, 3189 RA pts had received ≥1 course (pts may have received multiple courses) of RTX providing 9365.03 pt-yrs of follow-up. The overall rate of SIE in this population was 4.34 (95% CI: 3.93, 4.78) per 100 pt-yrs. Of pts who entered SFU, 283 pts were subsequently treated with another biologic (median time 8.5 mo [range: 0.1-52] after last RTX infusion). The largest group (n=230 pts) received TNFi after RTX. Median follow-up time after receipt of the subsequent biologic was 11 mo (range: 7—17 mo). At the time of receiving further BDMARD treatment, 83.0% had peripheral B-cell counts below lower limit of normal (LLN) (<80 cells/μL). 30.7% of 283 pts received their biologic within 6 mo of their last RTX infusion.  During treatment with RTX and prior to receipt of the biologic, this group of 283 pts had 6.01 SIEs per 100 pt-yrs (Table). Following initiation of BDMARD, the rate was 4.97 SIEs per 100 pt-yrs. Median time to SIE after initiating BDMARD was 11 mo (range: 2—21 mo). In 43 pts who received abatacept (ABA) as their 1^st BDMARD, there was 1 SIE before and 1 SIE after receiving ABA (97.7 total pt-yrs). Overall, the infections were variable and typical for RA pts. There were no opportunistic or fatal infections.

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Conclusion: In this updated analysis, the use of other biologic therapies in RA pts previously treated with RTX was not associated with an increase in the rate of serious infections in pts who received biologics or in the subgroup who received TNFi. The rate of serious infections is consistent with rates seen in long-term safety analyses (van Vollenhoven et al, A&R 2009;60[Suppl. 10]:1952).

Disclosure of Interest: M. Genovese Grant / Research Support from: GenentechF. Breedveld: None DeclaredP. Emery Grant / Research Support from: RocheS. Cohen Consultant for: GenentechE. Keystone Consultant for: GenentechE. Matteson Grant / Research Support from: GenentechL. Burke Employee of: RocheA. Chai Shareholder of: Genentech Employee of: GenentechW. Reiss Shareholder of: Genentech Employee of: GenentechM. Sweetser Shareholder of: Biogen Idec Employee of: Biogen IdecT. Shaw Employee of: Roche