I am suprised that i could not find any news of this study on this forum, it has been the biggest health news in norweig and in sweden (where i am ) this has given me such hope.
a synopsis is included below,
A study published on Oct. 19, 2011, in PLoS ONE reports on results of a double-blind, placebo-controlled trial of the drug rituximab in CFS. A team of researchers at two institutions in Bergen, Norway, led by Drs. ystein Fluge and Olav Mella, first observed marked recovery in a CFS patient who was treated for Hodgkins disease with cytotoxic chemotherapy. They followed that with a small study of rituximab, a monoclonal antibody treatment approved by the Food and Drug Administration (FDA) for five conditions: non-Hodgkins lymphoma (NHL); chronic lymphocytic leukemia; rheumatoid arthritis; Wegeners granulomatosis; and microscopic polyangiitis. Rituximab (also known as Rituxan) is administered intervenously (IV) during an overnight hospital stay for monitoring according to established protocols.
In the first case series, three CFS patients were treated with rituximab on an open-label basis, meaning that the physicians and the patients knew they were administering/receiving the drug. All three patients experienced significant improvement; two of them responded within three months and the third had a delayed response, occuring 5 1/2 - 9 months after treatment. This experience led the investigators to hypothesize that B cells of the immune system might play a significant role in CFS. Rituximab works by killing B cells that have a marker called CD20 on their surface and is used to rid the body of these cells that are overactive, too great in number or dysfunctional. A new population of healthy B cells is produced by the bodys stem cells. The positive results of this small open label trial led Drs. Fluge and Mella to conduct the larger study with a more rigorous design to test the effects of the drug compared to a placebo not expected to have therapeutic benefit.
Thirty patients meeting the 1994 Fukuda definition for CFS were enrolled in the study. Patients were between 18-65 years of age; 80 percent were female and duration of illness ranged from 8 months to 18 years. 21 of the 30 had defined or possible infectious onset of their illness, including mononucleosis, gastroenteritis, respiratory or urinary infection or other unspecified viral infection. Subjects were carefully screened for active infections with several viruses because rRituximab carries a risk of reactivating viruses when it depletes B cells needed to mount a healthy immune response, especially if faced with a viral infection. All subjects were tested using multiple assays for XMRV and MLV infection; no evidence was found. 21 of the subjects rated themselves as stable before the trial began; two were improving and seven were worsening. After the trial, the investigators compared all 30 patients symptoms to the Canadian clinical definition for ME/CFS. All but two met these criteria as well as the broader Fukuda criteria.
At random, half of the patients were assigned to treatment and half were assigned to receive placebo by the pharmacy, although neither the physicians, the nursing staff, nor the patients knew which individuals were receiving which infusion until after the study was completed. This is what is meant by the term double-blinded, placebo-controlled trial, a gold standard design used to minimize bias of either the physician or the patient.
Each subject in the study was evaluated closely using standardized symptom instruments before the study (baseline), and at 2, 4, 6, 8, 10 and 12 months after intervention. Immune system measurements were also taken. Each subject received two IVs, given two weeks apart. Patients who received rituximab were given 500 mg/m2. Saline was used for the placebo in this study. It is unclear whether the researchers were aware that IV-saline has been used in CFS to treat orthostatic intolerance-associated symptoms with some benefit, although its long-term use can be challenging due to the potential for infection.
There were no major adverse effects reported during the study. Minor effects were noted, but none led to withdrawal from the study. Two individuals did drop out, one due to pregnancy and another to pursue an alternative therapy. Both were in the group receiving placebo, although neither knew this at the time they withdrew.
Based on the analysis of results after the investigators were unblinded to which subjects received treatment and placebo, there was major response for at least six weeks in 9 of 15 patients who received rituximab, compared to one who received saline. There was one more person in each group who had moderate improvement. Overall, two-thirds of the Rituximab-treated group met the criteria for lasting improvement compared to 12 percent of the placebo group. This is a statistically significant result. Only one of the responders in the rituximab group showed an early response pattern, while the other nine started to improve 3-7 months after treatment. The responders in the rituximab group experienced an mean duration of improvement for 25 weeks. Two patients in the rituximab group and one in the placebo group have had lasting major responses for all CFS-related symptoms without signs of relapse, 32, 30 and 23 months after intervention, respectively. One of the individuals who responded to placebo was also one of the two subjects who did not fulfill Canadian criteria for ME/CFS. It is possible that both the responders to the saline placebo had orthostatic intolerance; however, this was not assessed or reported in the paper.
There do not appear to be substantial differing characteristics between the responders in the rituximab group and those who did not respond. There were no apparent differences in immune testing at baseline or after treatment. There was no difference in the modest adverse events reported between the responders and the non-responders. The investigators have started a new open-label trial of Rituximab with the two initial infusions given two weeks apart and then followed with maintenance infusions at 3, 6, 10 and 15 months. This study took more than three years to complete.
There do not appear to be substantial differing characteristics between the responders in the rituximab group and those who did not respond. There were no apparent differences in immune testing at baseline or after treatment. There was no difference in the modest adverse events reported between the responders and the non-responders. The investigators have started a new open-label trial of Rituximab with the two initial infusions given two weeks apart and then followed with maintenance infusions at 3, 6, 10 and 15 months. This study took more than three years to complete.
The authors state that the results support the concept of CFS as an autoimmune disease. They are working to identify the target for the autoimmune process. They assert that results of their study and the measures taken support the assumption that CFS is not primarily a mental health disorder. Additionally, they comment that the delayed response to B-cell depletion with rituximab is difficult to explain from a viral elimination mechanism and that the pattern is more consistent with gradual elimination of an autoantibody, perhaps by preferential elimination of short-lived pre-plasma cells. They recognize that their research requires follow-up with larger studies and that the suggested mechanism may apply to specific subsets of CFS patients. While there are risks associated with rituximab treatment, the authors argue, the persistent and often devastating symptoms of CFS and the very low quality of life in many sufferers justify the use of Rituximab in carefully evaluated CFS patients.
The results of this study showing that two infusions of rituximab may provide durable relief from CFS are extremely encouraging. The most exciting news from the study is the possibility of disease-modifying treatment for at least some people with CFS. This study also provides support for other possible approaches to repair immune abnormalities that have been identified in CFS patients. The application of a therapy approved for two types of cancer and rheumatoid arthritis validates the seriousness of the illness and demonstrates the large unmet need for effective treatment. We hope that its promising results will spur new investment from pharma, academic and government research institutions to meet this huge need. We congratulate the team in Bergen, Norway, for pioneering this approach, for the exciting results they have produced and the hope they have generated.
http://www.research1st.com/2011/10/...&utm_campaign=Feed:+Research1st+(Research1st)
http://www.research1st.com/2011/10/...&utm_campaign=Feed:+Research1st+(Research1st)
a synopsis is included below,
A study published on Oct. 19, 2011, in PLoS ONE reports on results of a double-blind, placebo-controlled trial of the drug rituximab in CFS. A team of researchers at two institutions in Bergen, Norway, led by Drs. ystein Fluge and Olav Mella, first observed marked recovery in a CFS patient who was treated for Hodgkins disease with cytotoxic chemotherapy. They followed that with a small study of rituximab, a monoclonal antibody treatment approved by the Food and Drug Administration (FDA) for five conditions: non-Hodgkins lymphoma (NHL); chronic lymphocytic leukemia; rheumatoid arthritis; Wegeners granulomatosis; and microscopic polyangiitis. Rituximab (also known as Rituxan) is administered intervenously (IV) during an overnight hospital stay for monitoring according to established protocols.
In the first case series, three CFS patients were treated with rituximab on an open-label basis, meaning that the physicians and the patients knew they were administering/receiving the drug. All three patients experienced significant improvement; two of them responded within three months and the third had a delayed response, occuring 5 1/2 - 9 months after treatment. This experience led the investigators to hypothesize that B cells of the immune system might play a significant role in CFS. Rituximab works by killing B cells that have a marker called CD20 on their surface and is used to rid the body of these cells that are overactive, too great in number or dysfunctional. A new population of healthy B cells is produced by the bodys stem cells. The positive results of this small open label trial led Drs. Fluge and Mella to conduct the larger study with a more rigorous design to test the effects of the drug compared to a placebo not expected to have therapeutic benefit.
Thirty patients meeting the 1994 Fukuda definition for CFS were enrolled in the study. Patients were between 18-65 years of age; 80 percent were female and duration of illness ranged from 8 months to 18 years. 21 of the 30 had defined or possible infectious onset of their illness, including mononucleosis, gastroenteritis, respiratory or urinary infection or other unspecified viral infection. Subjects were carefully screened for active infections with several viruses because rRituximab carries a risk of reactivating viruses when it depletes B cells needed to mount a healthy immune response, especially if faced with a viral infection. All subjects were tested using multiple assays for XMRV and MLV infection; no evidence was found. 21 of the subjects rated themselves as stable before the trial began; two were improving and seven were worsening. After the trial, the investigators compared all 30 patients symptoms to the Canadian clinical definition for ME/CFS. All but two met these criteria as well as the broader Fukuda criteria.
At random, half of the patients were assigned to treatment and half were assigned to receive placebo by the pharmacy, although neither the physicians, the nursing staff, nor the patients knew which individuals were receiving which infusion until after the study was completed. This is what is meant by the term double-blinded, placebo-controlled trial, a gold standard design used to minimize bias of either the physician or the patient.
Each subject in the study was evaluated closely using standardized symptom instruments before the study (baseline), and at 2, 4, 6, 8, 10 and 12 months after intervention. Immune system measurements were also taken. Each subject received two IVs, given two weeks apart. Patients who received rituximab were given 500 mg/m2. Saline was used for the placebo in this study. It is unclear whether the researchers were aware that IV-saline has been used in CFS to treat orthostatic intolerance-associated symptoms with some benefit, although its long-term use can be challenging due to the potential for infection.
There were no major adverse effects reported during the study. Minor effects were noted, but none led to withdrawal from the study. Two individuals did drop out, one due to pregnancy and another to pursue an alternative therapy. Both were in the group receiving placebo, although neither knew this at the time they withdrew.
Based on the analysis of results after the investigators were unblinded to which subjects received treatment and placebo, there was major response for at least six weeks in 9 of 15 patients who received rituximab, compared to one who received saline. There was one more person in each group who had moderate improvement. Overall, two-thirds of the Rituximab-treated group met the criteria for lasting improvement compared to 12 percent of the placebo group. This is a statistically significant result. Only one of the responders in the rituximab group showed an early response pattern, while the other nine started to improve 3-7 months after treatment. The responders in the rituximab group experienced an mean duration of improvement for 25 weeks. Two patients in the rituximab group and one in the placebo group have had lasting major responses for all CFS-related symptoms without signs of relapse, 32, 30 and 23 months after intervention, respectively. One of the individuals who responded to placebo was also one of the two subjects who did not fulfill Canadian criteria for ME/CFS. It is possible that both the responders to the saline placebo had orthostatic intolerance; however, this was not assessed or reported in the paper.
There do not appear to be substantial differing characteristics between the responders in the rituximab group and those who did not respond. There were no apparent differences in immune testing at baseline or after treatment. There was no difference in the modest adverse events reported between the responders and the non-responders. The investigators have started a new open-label trial of Rituximab with the two initial infusions given two weeks apart and then followed with maintenance infusions at 3, 6, 10 and 15 months. This study took more than three years to complete.
There do not appear to be substantial differing characteristics between the responders in the rituximab group and those who did not respond. There were no apparent differences in immune testing at baseline or after treatment. There was no difference in the modest adverse events reported between the responders and the non-responders. The investigators have started a new open-label trial of Rituximab with the two initial infusions given two weeks apart and then followed with maintenance infusions at 3, 6, 10 and 15 months. This study took more than three years to complete.
The authors state that the results support the concept of CFS as an autoimmune disease. They are working to identify the target for the autoimmune process. They assert that results of their study and the measures taken support the assumption that CFS is not primarily a mental health disorder. Additionally, they comment that the delayed response to B-cell depletion with rituximab is difficult to explain from a viral elimination mechanism and that the pattern is more consistent with gradual elimination of an autoantibody, perhaps by preferential elimination of short-lived pre-plasma cells. They recognize that their research requires follow-up with larger studies and that the suggested mechanism may apply to specific subsets of CFS patients. While there are risks associated with rituximab treatment, the authors argue, the persistent and often devastating symptoms of CFS and the very low quality of life in many sufferers justify the use of Rituximab in carefully evaluated CFS patients.
The results of this study showing that two infusions of rituximab may provide durable relief from CFS are extremely encouraging. The most exciting news from the study is the possibility of disease-modifying treatment for at least some people with CFS. This study also provides support for other possible approaches to repair immune abnormalities that have been identified in CFS patients. The application of a therapy approved for two types of cancer and rheumatoid arthritis validates the seriousness of the illness and demonstrates the large unmet need for effective treatment. We hope that its promising results will spur new investment from pharma, academic and government research institutions to meet this huge need. We congratulate the team in Bergen, Norway, for pioneering this approach, for the exciting results they have produced and the hope they have generated.
http://www.research1st.com/2011/10/...&utm_campaign=Feed:+Research1st+(Research1st)
http://www.research1st.com/2011/10/...&utm_campaign=Feed:+Research1st+(Research1st)
