Rituximab May Inhibit Joint Damage In RA Even Without Clinical Response:
Lack of clinical response to rituximab does not necessarily mean that joint damage is continuing unchecked, Dr. Edward Keystone reported at the annual meeting of the American College of Rheumatology.
That observation is based on findings from a phase III, randomized, double-blind trial of 517 patients with rheumatoid arthritis (RA) who had been refractory to treatment with one or more prior tumor necrosis factor (TNF) inhibitors. The data suggest that there is “an uncoupling in terms of the relationship between the clinical and radiographic outcomes of treatment with rituximab,” said Dr. Keystone, professor of medicine at the University of Toronto.
During the first 16 weeks of the trial, 209 patients received methotrexate plus placebo while 308 patients received methotrexate and rituximab (two 1-g infusions). After 16 weeks, rescue treatment with rituximab was allowed for placebo patients, and rescue with standard-of-care treatment was available for patients who were randomized to rituximab initially. An open-label extension phase at 24 weeks permitted retreatment with rituximab if patients had active disease but had responded initially to rituximab.
During the trial, the patients used an average dose of about 17 mg/week methotrexate but had an inadequate response to the drug. They also had failed treatment with a mean of about 2.5 previous disease-modifying antirheumatic drugs, not including methotrexate or TNF inhibitors.
At the end of 56 weeks, a significantly greater percentage of rituximab patients had achieved 20% improvement (based on American College of Rheumatology criteria) than did placebo patients. The rituximab patients also had significantly less radiographic disease progression on the erosion and joint space-narrowing subsets of the Genant-modified Sharp score and the total value of the that scoring method.
Among the subgroup of patients who did not achieve an ACR 20 level of response at 24 weeks, those who received rituximab still had significantly less radiographic disease progression than did placebo patients. The degree of progression was similar to that seen in patients who achieved an ACR 20 response.
In patients who were assigned initially to placebo, the amount of radiographic progression seen at 56 weeks (based on Genant-modified Sharp scores) rose steeply as the number of swollen joints in individual patients at 24 weeks increased from 2 or fewer to 13 or more. The relationship between radiographic progression and the number of swollen joints was not seen in those who were randomized to rituximab.
These results may suggest that the ACR 20 criteria itself may not be a “perfect index” and that the number of swollen joints corresponded better to radiographic progression, Dr. Keystone said.
Only 36 of 186 (19%) placebo patients completed 56 weeks without receiving any rituximab. Other placebo patients received at least one course of rituximab after 16 weeks, but most of them received the drug later than 16 weeks on average. “That time was not enough to show the difference” in clinical and radiographic responses between the two groups, he said.
“It's very impressive that 80% of the placebo [patients] were going on an active agent yet you still see a 50% difference between active agent and placebo. I think it's striking, particularly in a population of patients that already failed an average of 1.5 TNF inhibitors,” said Dr. Keystone, who reported receiving consulting fees or other remuneration from Genentech Inc. and serving on the company's speakers' bureau. Genentech manufactures rituximab.
One audience member suggested that rituximab's effect on radiographic progression without a clinical response may just reflect the total amount of active treatment that each patient had received up to that point, which then can be seen with x-ray. Such findings have been described for a 12-month trial comparing methotrexate, leflunomide, and placebo.
hi lynn i think it will be a while yet before we find out
what these meds are capable or incapable of..
Boney...
Rituxan has been a great med for me. It is the first med in almost 9 years that has worked and continues to work well. It took a long time for it to kick in and I haven't had any new damage :)hi lynn that is good news.. 9 yrs is a long haul ..
i hope you benefit for a long time to come..
Boney
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