Treating Ankylosing Spondylitis Refractory to TNF-inhibition
Treating Ankylosing Spondylitis Refractory to TNF-inhibition
The chimeric anti-CD20 monoclonal antibody rituximab approved for the treatment of lymphoma in 1997 was the first B-cell agent that was licensed for the treatment of RA. Ever since histologic studies showed B cell clusters in the subchondral bone marrow of the spine in patients with AS, immunotherapies targeting B cells have been of substantial interest. One clinical trial, registry data from France and three case reports have been published in the last years.
The results of an open-label trial with 20 patients with active AS have been recently reported: 10 patients who had never received TNF blockers and 10 who failed treatment with TNF blockers. Patients received 1000mg rituximab i.v. within 2 weeks. The primary endpoint ASAS 20 was reached by 40% of the combined patients at week 24, and 15% even achieved partial remission. All changes were more pronounced in TNF-inhibitor naive patients. Most patients (90%) continued the study through week 24. Active inflammatory changes on spinal MRI as assessed by the Berlin MRI score did not decrease. The authors concluded that rituximab may have some efficacy in TNF-inhibitor naive patients but does not seem to be efficacious in patients with AS who had not responded to TNF inhibitors.
The French registry data did not show a decrease in disease activity of eight patients with SpA, seven of whom had previously received anti-TNF treatment, three with AS, two with peripheral SpA and three with PsA.
The case reports also showed conflicting results. Successful therapy with rituximab in a patient with active AS and peripheral arthritis who had hepatitis B was reported from Spain; within 7 months the BASDAI decreased from 8.6 to 1, and the swollen joint count improved from 8 to 0 within 2 months. A marked reduction of bone marrow edema in the SIJ as detected by MRI was reported in a TNF-inhibitor naive Chinese AS patient 14 weeks after two 500mg rituximab infusions. In contrast, a French AS patient did obviously not respond to 1 g of rituximab.
In summary, TNF-inhibitor naive AS patients seem to respond better to B cell depletion compared with patients who had already failed to TNF blocker therapy. However, the low patient numbers and the open trial design do not allow valid conclusions.
Rituximab
The chimeric anti-CD20 monoclonal antibody rituximab approved for the treatment of lymphoma in 1997 was the first B-cell agent that was licensed for the treatment of RA. Ever since histologic studies showed B cell clusters in the subchondral bone marrow of the spine in patients with AS, immunotherapies targeting B cells have been of substantial interest. One clinical trial, registry data from France and three case reports have been published in the last years.
The results of an open-label trial with 20 patients with active AS have been recently reported: 10 patients who had never received TNF blockers and 10 who failed treatment with TNF blockers. Patients received 1000mg rituximab i.v. within 2 weeks. The primary endpoint ASAS 20 was reached by 40% of the combined patients at week 24, and 15% even achieved partial remission. All changes were more pronounced in TNF-inhibitor naive patients. Most patients (90%) continued the study through week 24. Active inflammatory changes on spinal MRI as assessed by the Berlin MRI score did not decrease. The authors concluded that rituximab may have some efficacy in TNF-inhibitor naive patients but does not seem to be efficacious in patients with AS who had not responded to TNF inhibitors.
The French registry data did not show a decrease in disease activity of eight patients with SpA, seven of whom had previously received anti-TNF treatment, three with AS, two with peripheral SpA and three with PsA.
The case reports also showed conflicting results. Successful therapy with rituximab in a patient with active AS and peripheral arthritis who had hepatitis B was reported from Spain; within 7 months the BASDAI decreased from 8.6 to 1, and the swollen joint count improved from 8 to 0 within 2 months. A marked reduction of bone marrow edema in the SIJ as detected by MRI was reported in a TNF-inhibitor naive Chinese AS patient 14 weeks after two 500mg rituximab infusions. In contrast, a French AS patient did obviously not respond to 1 g of rituximab.
In summary, TNF-inhibitor naive AS patients seem to respond better to B cell depletion compared with patients who had already failed to TNF blocker therapy. However, the low patient numbers and the open trial design do not allow valid conclusions.