A New Era in Lupus Therapy
A New Era in Lupus Therapy
A somewhat different situation from that of rituximab has emerged regarding the T-cell costimulation blocker abatacept. This biologic has been approved for rheumatoid arthritis for almost a decade, and although theoretical considerations and animal models suggest a potential benefit in SLE, off-label use has not been reported on a large scale.
Similar to the situation with rituximab, trials of abatacept in both nonrenal lupus and lupus nephritis failed, and again, the interpretation is somewhat controversial. In the nonrenal trial, the primary endpoint revealed no difference, but a subset analysis showed a clear difference for patients with arthritis that favored abatacept over placebo. This might suggest a specific potential for abatacept in that subset of patients, although such a finding must be confirmed in subsequent studies.
In the lupus nephritis trial of abatacept, both the control group and the active treatment group had very low rates of renal response. This was discussed extensively in a publication describing a post hoc analysis that underscored the importance of choosing the correct outcomes: If other renal outcome definitions had been applied, the abatacept trial would almost certainly have been successful.
At this time, it is unclear whether additional industry-sponsored trials with abatacept are in the cards. However, the Immune Tolerance Network has an ongoing investigator-initiated clinical trial of abatacept in lupus nephritis, with the added important feature that the biologic is used in combination with cyclophosphamide, in recognition of the evidence from mouse models that a synergistic effect could be present.
It's All in the Outcomes
A somewhat different situation from that of rituximab has emerged regarding the T-cell costimulation blocker abatacept. This biologic has been approved for rheumatoid arthritis for almost a decade, and although theoretical considerations and animal models suggest a potential benefit in SLE, off-label use has not been reported on a large scale.
Similar to the situation with rituximab, trials of abatacept in both nonrenal lupus and lupus nephritis failed, and again, the interpretation is somewhat controversial. In the nonrenal trial, the primary endpoint revealed no difference, but a subset analysis showed a clear difference for patients with arthritis that favored abatacept over placebo. This might suggest a specific potential for abatacept in that subset of patients, although such a finding must be confirmed in subsequent studies.
In the lupus nephritis trial of abatacept, both the control group and the active treatment group had very low rates of renal response. This was discussed extensively in a publication describing a post hoc analysis that underscored the importance of choosing the correct outcomes: If other renal outcome definitions had been applied, the abatacept trial would almost certainly have been successful.
At this time, it is unclear whether additional industry-sponsored trials with abatacept are in the cards. However, the Immune Tolerance Network has an ongoing investigator-initiated clinical trial of abatacept in lupus nephritis, with the added important feature that the biologic is used in combination with cyclophosphamide, in recognition of the evidence from mouse models that a synergistic effect could be present.
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