Clinical Benefits Lacking After B-Cell Depletion in AS

LIVERPOOL, ENGLAND — B-cell depletion with rituximab showed benefits on magnetic resonance imaging for patients with active ankylosing spondylitis in a pilot study, but clinical effects were less pronounced, said Dr. Jonathan C. Packham of Keele (England) University.

Populations of CD20-positive B cells have been identified on histologic analysis of the spine in AS, and B-cell-producing germinal centers similar to those seen in RA have been found in the sacroiliac joints in AS, suggesting anti-CD20 treatment might have beneficial therapeutic effects. “We therefore performed a 6-month open-label study of rituximab … using MRI to evaluate its effects on spinal enthesitis,” Dr. Packham said at the annual meeting of the British Society for Rheumatology.

Rituximab was administered as two infusions of 1 g each, 2 weeks apart, in seven patients. Clinical assessments, made at four points during the study, included inflammatory markers, tender and swollen joint counts, patient global assessment, nocturnal and total back pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and AS quality of life (ASQOL).

At baseline, mean BASDAI and BASFI were 7.8 and 7.9, respectively, and all patients had C-reactive protein levels higher than 10 mg/dL. The mean number of sites of MRI-determined enthesitis/osteitis per patient fell by 49% between baseline and 6 months, from 19.4 to 9.9, which was statistically significant, Dr. Packham said. Significant improvements on MRI were seen in both lumbar spine and sacroiliac joints. The number of swollen joints fell from a mean of 3.9 to 2.6.

There was a nonsignificant trend in improvement in BASDAI and BASFI, with both indices decreased by 1.6 units over 6 months. There were no detectable changes in erythrocyte sedimentation rate, C-reactive protein, or ASQOL scores, however.

In an interview, Dr. Packham said he remains uncertain about whether these results represent a true effect of rituximab or the disease process itself settling down. “Levels of inflammation decreased by half on MRI, but this didn't appear to translate into clinical improvements. The response to rituximab does not seem to be as good as with anti-TNF agents in [AS],” he said. “But it's early days yet. Two other pilot studies are ongoing in Europe.”

Dr. Packham disclosed receiving an unrestricted educational grant from F. Hoffmann-La Roche Ltd.

LIVERPOOL, ENGLAND — B-cell depletion with rituximab showed benefits on magnetic resonance imaging for patients with active ankylosing spondylitis in a pilot study, but clinical effects were less pronounced, said Dr. Jonathan C. Packham of Keele (England) University.

Populations of CD20-positive B cells have been identified on histologic analysis of the spine in AS, and B-cell-producing germinal centers similar to those seen in RA have been found in the sacroiliac joints in AS, suggesting anti-CD20 treatment might have beneficial therapeutic effects. “We therefore performed a 6-month open-label study of rituximab … using MRI to evaluate its effects on spinal enthesitis,” Dr. Packham said at the annual meeting of the British Society for Rheumatology.

Rituximab was administered as two infusions of 1 g each, 2 weeks apart, in seven patients. Clinical assessments, made at four points during the study, included inflammatory markers, tender and swollen joint counts, patient global assessment, nocturnal and total back pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and AS quality of life (ASQOL).

At baseline, mean BASDAI and BASFI were 7.8 and 7.9, respectively, and all patients had C-reactive protein levels higher than 10 mg/dL. The mean number of sites of MRI-determined enthesitis/osteitis per patient fell by 49% between baseline and 6 months, from 19.4 to 9.9, which was statistically significant, Dr. Packham said. Significant improvements on MRI were seen in both lumbar spine and sacroiliac joints. The number of swollen joints fell from a mean of 3.9 to 2.6.

There was a nonsignificant trend in improvement in BASDAI and BASFI, with both indices decreased by 1.6 units over 6 months. There were no detectable changes in erythrocyte sedimentation rate, C-reactive protein, or ASQOL scores, however.

In an interview, Dr. Packham said he remains uncertain about whether these results represent a true effect of rituximab or the disease process itself settling down. “Levels of inflammation decreased by half on MRI, but this didn't appear to translate into clinical improvements. The response to rituximab does not seem to be as good as with anti-TNF agents in [AS],” he said. “But it's early days yet. Two other pilot studies are ongoing in Europe.”

Dr. Packham disclosed receiving an unrestricted educational grant from F. Hoffmann-La Roche Ltd.

LIVERPOOL, ENGLAND — B-cell depletion with rituximab showed benefits on magnetic resonance imaging for patients with active ankylosing spondylitis in a pilot study, but clinical effects were less pronounced, said Dr. Jonathan C. Packham of Keele (England) University.

Populations of CD20-positive B cells have been identified on histologic analysis of the spine in AS, and B-cell-producing germinal centers similar to those seen in RA have been found in the sacroiliac joints in AS, suggesting anti-CD20 treatment might have beneficial therapeutic effects. “We therefore performed a 6-month open-label study of rituximab … using MRI to evaluate its effects on spinal enthesitis,” Dr. Packham said at the annual meeting of the British Society for Rheumatology.

Rituximab was administered as two infusions of 1 g each, 2 weeks apart, in seven patients. Clinical assessments, made at four points during the study, included inflammatory markers, tender and swollen joint counts, patient global assessment, nocturnal and total back pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and AS quality of life (ASQOL).

At baseline, mean BASDAI and BASFI were 7.8 and 7.9, respectively, and all patients had C-reactive protein levels higher than 10 mg/dL. The mean number of sites of MRI-determined enthesitis/osteitis per patient fell by 49% between baseline and 6 months, from 19.4 to 9.9, which was statistically significant, Dr. Packham said. Significant improvements on MRI were seen in both lumbar spine and sacroiliac joints. The number of swollen joints fell from a mean of 3.9 to 2.6.

There was a nonsignificant trend in improvement in BASDAI and BASFI, with both indices decreased by 1.6 units over 6 months. There were no detectable changes in erythrocyte sedimentation rate, C-reactive protein, or ASQOL scores, however.

In an interview, Dr. Packham said he remains uncertain about whether these results represent a true effect of rituximab or the disease process itself settling down. “Levels of inflammation decreased by half on MRI, but this didn't appear to translate into clinical improvements. The response to rituximab does not seem to be as good as with anti-TNF agents in [AS],” he said. “But it's early days yet. Two other pilot studies are ongoing in Europe.”

Dr. Packham disclosed receiving an unrestricted educational grant from F. Hoffmann-La Roche Ltd.