While the tumor necrosis factor (TNF) inhibiting drugs have been a great addition in the treatment of rheumatoid arthritis, it must be remembered that they have a failure rate in up to 40% of patients. Thus, B-lymphocyte cells became one more target; TNF is not the only thing that can be attacked and give improvement in rheumatoid arthritis.
Rituxan is one approach to targeting those B cells. Rituxan does this by depleting B cells, cells participating in the abnormal immune system in rheumatoid arthritis. Rituxan in combination with methotrexate is approved for patients with rheumatoid arthritis who have had a less than ideal response to at least one TNF inhibitor.
The dosage regimen has, in general, been two infusions of 1,000 mg given 2 weeks apart. The results in the following six months are very impressive. But rheumatoid arthritis is a chronic disease, and many patients need another course of therapy. Right now, insurance companies are very hesitant to approve repeat courses of Rituxan. They have no qualms about indefinite Remicade, or even Orencia. But there, apparently, is something finite-sounding about those two 1,000 mg infusions to the insurance companies.
Last month's issue of Arthritis and Rheumatism featured the results of an open label analysis of the safety and efficacy of Rituxan in patients who received two or more courses.
Researchers found that Rituxan remained an effective drug with repeat courses; and in fact there may even be a further reduction in the activity of rheumatoid arthritis with repeated courses of Rituxan. In addition, these repeated courses of Rituxan were tolerated well by patients, and resulted in no additional safety concerns.
The majority of the adverse reactions appear to be associated with the actual infusion of the Rituxan into the patient's vein. Infections appear to be a problem more in the first three months, perhaps related to the corticosteroids the patients receive prior to the arthritis drug.
Interestingly, the incidence of acute infusion-related side effects decreased with additional treatments. This could be because so many B cells have already been destroyed by prior Rituxan infusions. It is well known that that destruction of B cells leads to fever, chills, nausea, vomiting, low blood pressure, and shortness of breath. The less B cells circulating, the less destroyed, and therefore, fewer of these nasty side effects.
There was no unusual increase in the rate of cancer or deaths among the patients receiving repeat courses of Rituxan. The rate of infection remained unchanged with additional Rituxan dosages. And there were no unusual infections or tuberculosis cases reported. Overall, the rate of infection among the Rituxan patients appeared to be no different from that seen among rheumatoid arthritis patients treated with the TNF inhibitors Enbrel, Humira and Remicade.
In conclusion, repeated courses of Rituxan appear to produce continued benefit in the rheumatoid arthritis patient. Importantly, there is no increased incidence of side effects within the time frame studied. However, it remains an expensive drug. It remains to be seen as to whether indefinite repeated infusions of Rituxan are the most effective way to treat a chronic illness such as rheumatoid arthritis. It remains to be seen whether yet-to-be discovered side effects will manifest themselves given a few more years. For now, the data favor Rituxan.
Hopefully, the insurance companies appreciate this.
Published On: January 11, 2008