https://bora.uib.no/bora-xmlui/bits...esis_2024_rekeland.pdf?sequence=1&isAllowed=y
Fluge & Mellor‘s full follow up paper has not yet been published, but this PHD thesis publishes alot of the data in advance. The slides are from Fluge’s talk at the 2023 Charite conference.
Cyc is impossible to blind, so trials for autoimmune diseases use alternative treatment or historical control groups. At six years there was little difference between rituximab and placebo patients so they can be treated as one large group. This is as good of a control sample as would be found in many studies of cyc for autoimmune disease. Both groups are individually big enough as a control sample.
At six years the cyc patients had improved by an average of 13.7 points more than the combined rtx study patients. There is a 1/20 chance the group difference is pure coincidence. Half of the cyc patients account for most of this difference, improving by an average of 24.4 points more than rtx combined group. This is a huge difference in quality of life.
Fewer cyc patients reported worsening than combined rtx study patients. The sample is too small prove a reduced risk, but it does suggest that the risk is probably not increased.
“At six-year follow-up in the cyclophosphamide group, 44.1% had an SF-36 PF > 70 at six years, compared to 27.6% in the rituximab group and 20.4 % in the placebo group. We chose a cutoff for at 70 points, because that would indicate a substantial improvement. The mean SF-36 PF at baseline was in the range 30-35 (for all groups).
SF-36 PF > 90, i.e., scores close to the normal population range, was achieved by 17.6% of the cyclophosphamide patients, 8.6% of the rituximab patients, and 7.4% of the placebo patients.”
It is difficult to dismiss the group difference as placebo for the following reasons.
1. Average time to first response in cyc patients was five and a half months which is not typical for a placebo effect. There was no prior data that would have made anyone expect this.
2. Cyclophosphamide outperformed rtx & placebo before unblinding. There was more hype and prior data for rituximab which could in theory have promoted a stronger placebo effect than cyclophosphamide.
3. Cyc patients improved by 5 points between 18 months and six years, while rtx active patients declined by about 4. It is understandable that placebo patients would stop improving or relapse after unblinding, but there is no explanation for cyc patients experiencing a long term placebo effect but not rtx active patients.
“In the CycloME study 15.0% worked part-time and no-one worked full-time at baseline. At six years (among 34 participants), six were working part-time and four were working full-time (29.4% in total). In the RituxME trial, four worked part-time, one worked full-time and three were students at baseline (5.3% in total). After six years (among 112 participants), one worked part-time, three worked full-time and two were students (4.5%). Doubling the number of people working part or full-time in the CycloME trial is important both for the patients and society.”
Fluge & Mellor‘s full follow up paper has not yet been published, but this PHD thesis publishes alot of the data in advance. The slides are from Fluge’s talk at the 2023 Charite conference.
Cyc is impossible to blind, so trials for autoimmune diseases use alternative treatment or historical control groups. At six years there was little difference between rituximab and placebo patients so they can be treated as one large group. This is as good of a control sample as would be found in many studies of cyc for autoimmune disease. Both groups are individually big enough as a control sample.
At six years the cyc patients had improved by an average of 13.7 points more than the combined rtx study patients. There is a 1/20 chance the group difference is pure coincidence. Half of the cyc patients account for most of this difference, improving by an average of 24.4 points more than rtx combined group. This is a huge difference in quality of life.
Fewer cyc patients reported worsening than combined rtx study patients. The sample is too small prove a reduced risk, but it does suggest that the risk is probably not increased.
“At six-year follow-up in the cyclophosphamide group, 44.1% had an SF-36 PF > 70 at six years, compared to 27.6% in the rituximab group and 20.4 % in the placebo group. We chose a cutoff for at 70 points, because that would indicate a substantial improvement. The mean SF-36 PF at baseline was in the range 30-35 (for all groups).
SF-36 PF > 90, i.e., scores close to the normal population range, was achieved by 17.6% of the cyclophosphamide patients, 8.6% of the rituximab patients, and 7.4% of the placebo patients.”
It is difficult to dismiss the group difference as placebo for the following reasons.
1. Average time to first response in cyc patients was five and a half months which is not typical for a placebo effect. There was no prior data that would have made anyone expect this.
2. Cyclophosphamide outperformed rtx & placebo before unblinding. There was more hype and prior data for rituximab which could in theory have promoted a stronger placebo effect than cyclophosphamide.
3. Cyc patients improved by 5 points between 18 months and six years, while rtx active patients declined by about 4. It is understandable that placebo patients would stop improving or relapse after unblinding, but there is no explanation for cyc patients experiencing a long term placebo effect but not rtx active patients.
“In the CycloME study 15.0% worked part-time and no-one worked full-time at baseline. At six years (among 34 participants), six were working part-time and four were working full-time (29.4% in total). In the RituxME trial, four worked part-time, one worked full-time and three were students at baseline (5.3% in total). After six years (among 112 participants), one worked part-time, three worked full-time and two were students (4.5%). Doubling the number of people working part or full-time in the CycloME trial is important both for the patients and society.”
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