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Aromatase inhibitor-induced arthralgia substantially improved in women who received omega-3 fatty acid capsules, as well as in those who took placebo, according to a study published online May 4 in the Journal of Clinical Oncology.
Brief Pain Inventory (BPI) worst pain scores were significantly lower than were baseline scores after treatment with O3-FAs and placebo. On the 10-point scale, the median scores reported by women taking O3-FAs were lower by 1.69, 1.74, and 2.23 at 6, 12, and 24 weeks, respectively (P < .001). For those taking placebo, the scores also were significantly lower: 1.36, 1.50, and 1.81 points at 6, 12, and 24 weeks respectively (P < .001). Differences between the groups were not significant, reported Dr. Dawn Hershman of the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, and associates (J. Clin. Onc. 2015 May 4 [doi: 10.1200/JCO.2014.59.5595]).
“The improvement in symptoms in both the treatment and placebo groups was unexpected. The magnitude of the expected placebo effect reported in the literature can vary from 6% to 59% and can be higher in symptom-management studies. We found an effect >50%,” Dr. Hershman and associates wrote.
The large placebo effect may have resulted from a number of factors, including the natural history of arthralgia (which can improve over time), the soy/corn oil ingredients in the placebo capsule, or O3-FA contamination in the placebo arm due to supplementation by patients.
There are no proven therapies for AI-associated arthralgia, and its mechanism is unclear. Evidence suggests that inflammation may play a role. Given that studies have shown O3-FAs may benefit symptoms of rheumatoid arthritis, this multicenter, placebo controlled trial evaluated whether O3-FAs reduce pain and stiffness in 249 women undergoing adjuvant AI therapy for early-stage breast cancer.
At week 12, patients who received O3-FAs had significantly decreased serum triglyceride levels (–22.1 mg/dL, P < .001) and increased HDL (2.9 mg/dL, P < .007). Triglyceride and HDL levels for the placebo arm did not significantly change, which suggests that O3-FA contamination in the placebo arm was not a factor in the high placebo effect. Other serum measures (cholesterol, CRP, and LDL) did not significantly change for either group, Dr. Hershman and associates said.
The placebo effect is related to patient expectations and perceptions of treatment. It is heightened with a supportive patient-provider relationship and typically diminished in blinded clinical trials where patients do not know if they are receiving the active drug. However, in clinical trials that have evaluated symptom management, substantial placebo effects were more common. This observation points to the importance of placebo-controlled, randomized trials vs. uncontrolled trials for symptom management therapies.
The larger-than-expected placebo response in the Hershman et. al. study may have resulted from several factors, including O3-FA supplementation causing placebo contamination, ingredients within the placebo capsule, the natural history of AIMSS, and patient selection.
Because O3-FAs are readily available as supplements, placebo contamination should be considered. The authors examined a surrogate marker for exposure, longitudinal change in triglycerides, and found only the active arm had decreased triglyceride levels. This observation suggests that participants in the placebo arm were not significantly exposed to O3-FAs.
The ingredients of the placebo capsule, soybean oil or other components, may have contributed to symptom improvement. If AIMSS is related to estrogen deprivation, estrogenic compounds in the placebo may have affected symptoms.
Previous studies indicate that many patients do not spontaneously improve over time, as would be the case if the natural history of AIMSS accounted for the high placebo effect.
Regarding the patients enrolled in the study, there is no way to definitively determine if their pain and stiffness was caused by AIs; distinguishing between AIMSS and worsening of osteoarthritis in this patient population with high baseline joint pain is difficult. It is possible that patients with preexisting musculoskeletal pain not related to AIs participated in this study, particularly since there is a low perceived toxicity of the drug.
Patients enrolled in this trial may have experienced symptom improvement solely due to the expectation of benefit by participation in the trial. A similar placebo response was reported in a controlled trial of modafinil for fatigue.
The results of this well-conducted SWOG trial clearly demonstrate that acknowledging and controlling for placebo effects is crucial to high-quality research in the field of symptom management.
Dr. N. Lynn Henry is assistant professor in the division of hematology/oncology, department of internal medicine, at the University of Michigan, Ann Arbor. Dr. Jennifer Griggs is professor of medicine in the division of hematology/oncology and director of the breast cancer survivorship program at the University of Michigan Comprehensive Cancer Center, Ann Arbor. Dr. Henry reported receiving research funding from Sanofi-Aventis, BioMarin, and Celldex. These comments were taken from an editorial accompanying the report by Hershman et al. (J. Clin. Onc. 2015 May 4 [doi:10.1200/JCO.2015.61.1004]).
The placebo effect is related to patient expectations and perceptions of treatment. It is heightened with a supportive patient-provider relationship and typically diminished in blinded clinical trials where patients do not know if they are receiving the active drug. However, in clinical trials that have evaluated symptom management, substantial placebo effects were more common. This observation points to the importance of placebo-controlled, randomized trials vs. uncontrolled trials for symptom management therapies.
The larger-than-expected placebo response in the Hershman et. al. study may have resulted from several factors, including O3-FA supplementation causing placebo contamination, ingredients within the placebo capsule, the natural history of AIMSS, and patient selection.
Because O3-FAs are readily available as supplements, placebo contamination should be considered. The authors examined a surrogate marker for exposure, longitudinal change in triglycerides, and found only the active arm had decreased triglyceride levels. This observation suggests that participants in the placebo arm were not significantly exposed to O3-FAs.
The ingredients of the placebo capsule, soybean oil or other components, may have contributed to symptom improvement. If AIMSS is related to estrogen deprivation, estrogenic compounds in the placebo may have affected symptoms.
Previous studies indicate that many patients do not spontaneously improve over time, as would be the case if the natural history of AIMSS accounted for the high placebo effect.
Regarding the patients enrolled in the study, there is no way to definitively determine if their pain and stiffness was caused by AIs; distinguishing between AIMSS and worsening of osteoarthritis in this patient population with high baseline joint pain is difficult. It is possible that patients with preexisting musculoskeletal pain not related to AIs participated in this study, particularly since there is a low perceived toxicity of the drug.
Patients enrolled in this trial may have experienced symptom improvement solely due to the expectation of benefit by participation in the trial. A similar placebo response was reported in a controlled trial of modafinil for fatigue.
The results of this well-conducted SWOG trial clearly demonstrate that acknowledging and controlling for placebo effects is crucial to high-quality research in the field of symptom management.
Dr. N. Lynn Henry is assistant professor in the division of hematology/oncology, department of internal medicine, at the University of Michigan, Ann Arbor. Dr. Jennifer Griggs is professor of medicine in the division of hematology/oncology and director of the breast cancer survivorship program at the University of Michigan Comprehensive Cancer Center, Ann Arbor. Dr. Henry reported receiving research funding from Sanofi-Aventis, BioMarin, and Celldex. These comments were taken from an editorial accompanying the report by Hershman et al. (J. Clin. Onc. 2015 May 4 [doi:10.1200/JCO.2015.61.1004]).
The placebo effect is related to patient expectations and perceptions of treatment. It is heightened with a supportive patient-provider relationship and typically diminished in blinded clinical trials where patients do not know if they are receiving the active drug. However, in clinical trials that have evaluated symptom management, substantial placebo effects were more common. This observation points to the importance of placebo-controlled, randomized trials vs. uncontrolled trials for symptom management therapies.
The larger-than-expected placebo response in the Hershman et. al. study may have resulted from several factors, including O3-FA supplementation causing placebo contamination, ingredients within the placebo capsule, the natural history of AIMSS, and patient selection.
Because O3-FAs are readily available as supplements, placebo contamination should be considered. The authors examined a surrogate marker for exposure, longitudinal change in triglycerides, and found only the active arm had decreased triglyceride levels. This observation suggests that participants in the placebo arm were not significantly exposed to O3-FAs.
The ingredients of the placebo capsule, soybean oil or other components, may have contributed to symptom improvement. If AIMSS is related to estrogen deprivation, estrogenic compounds in the placebo may have affected symptoms.
Previous studies indicate that many patients do not spontaneously improve over time, as would be the case if the natural history of AIMSS accounted for the high placebo effect.
Regarding the patients enrolled in the study, there is no way to definitively determine if their pain and stiffness was caused by AIs; distinguishing between AIMSS and worsening of osteoarthritis in this patient population with high baseline joint pain is difficult. It is possible that patients with preexisting musculoskeletal pain not related to AIs participated in this study, particularly since there is a low perceived toxicity of the drug.
Patients enrolled in this trial may have experienced symptom improvement solely due to the expectation of benefit by participation in the trial. A similar placebo response was reported in a controlled trial of modafinil for fatigue.
The results of this well-conducted SWOG trial clearly demonstrate that acknowledging and controlling for placebo effects is crucial to high-quality research in the field of symptom management.
Dr. N. Lynn Henry is assistant professor in the division of hematology/oncology, department of internal medicine, at the University of Michigan, Ann Arbor. Dr. Jennifer Griggs is professor of medicine in the division of hematology/oncology and director of the breast cancer survivorship program at the University of Michigan Comprehensive Cancer Center, Ann Arbor. Dr. Henry reported receiving research funding from Sanofi-Aventis, BioMarin, and Celldex. These comments were taken from an editorial accompanying the report by Hershman et al. (J. Clin. Onc. 2015 May 4 [doi:10.1200/JCO.2015.61.1004]).
Aromatase inhibitor-induced arthralgia substantially improved in women who received omega-3 fatty acid capsules, as well as in those who took placebo, according to a study published online May 4 in the Journal of Clinical Oncology.
Brief Pain Inventory (BPI) worst pain scores were significantly lower than were baseline scores after treatment with O3-FAs and placebo. On the 10-point scale, the median scores reported by women taking O3-FAs were lower by 1.69, 1.74, and 2.23 at 6, 12, and 24 weeks, respectively (P < .001). For those taking placebo, the scores also were significantly lower: 1.36, 1.50, and 1.81 points at 6, 12, and 24 weeks respectively (P < .001). Differences between the groups were not significant, reported Dr. Dawn Hershman of the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, and associates (J. Clin. Onc. 2015 May 4 [doi: 10.1200/JCO.2014.59.5595]).
“The improvement in symptoms in both the treatment and placebo groups was unexpected. The magnitude of the expected placebo effect reported in the literature can vary from 6% to 59% and can be higher in symptom-management studies. We found an effect >50%,” Dr. Hershman and associates wrote.
The large placebo effect may have resulted from a number of factors, including the natural history of arthralgia (which can improve over time), the soy/corn oil ingredients in the placebo capsule, or O3-FA contamination in the placebo arm due to supplementation by patients.
There are no proven therapies for AI-associated arthralgia, and its mechanism is unclear. Evidence suggests that inflammation may play a role. Given that studies have shown O3-FAs may benefit symptoms of rheumatoid arthritis, this multicenter, placebo controlled trial evaluated whether O3-FAs reduce pain and stiffness in 249 women undergoing adjuvant AI therapy for early-stage breast cancer.
At week 12, patients who received O3-FAs had significantly decreased serum triglyceride levels (–22.1 mg/dL, P < .001) and increased HDL (2.9 mg/dL, P < .007). Triglyceride and HDL levels for the placebo arm did not significantly change, which suggests that O3-FA contamination in the placebo arm was not a factor in the high placebo effect. Other serum measures (cholesterol, CRP, and LDL) did not significantly change for either group, Dr. Hershman and associates said.
Aromatase inhibitor-induced arthralgia substantially improved in women who received omega-3 fatty acid capsules, as well as in those who took placebo, according to a study published online May 4 in the Journal of Clinical Oncology.
Brief Pain Inventory (BPI) worst pain scores were significantly lower than were baseline scores after treatment with O3-FAs and placebo. On the 10-point scale, the median scores reported by women taking O3-FAs were lower by 1.69, 1.74, and 2.23 at 6, 12, and 24 weeks, respectively (P < .001). For those taking placebo, the scores also were significantly lower: 1.36, 1.50, and 1.81 points at 6, 12, and 24 weeks respectively (P < .001). Differences between the groups were not significant, reported Dr. Dawn Hershman of the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, and associates (J. Clin. Onc. 2015 May 4 [doi: 10.1200/JCO.2014.59.5595]).
“The improvement in symptoms in both the treatment and placebo groups was unexpected. The magnitude of the expected placebo effect reported in the literature can vary from 6% to 59% and can be higher in symptom-management studies. We found an effect >50%,” Dr. Hershman and associates wrote.
The large placebo effect may have resulted from a number of factors, including the natural history of arthralgia (which can improve over time), the soy/corn oil ingredients in the placebo capsule, or O3-FA contamination in the placebo arm due to supplementation by patients.
There are no proven therapies for AI-associated arthralgia, and its mechanism is unclear. Evidence suggests that inflammation may play a role. Given that studies have shown O3-FAs may benefit symptoms of rheumatoid arthritis, this multicenter, placebo controlled trial evaluated whether O3-FAs reduce pain and stiffness in 249 women undergoing adjuvant AI therapy for early-stage breast cancer.
At week 12, patients who received O3-FAs had significantly decreased serum triglyceride levels (–22.1 mg/dL, P < .001) and increased HDL (2.9 mg/dL, P < .007). Triglyceride and HDL levels for the placebo arm did not significantly change, which suggests that O3-FA contamination in the placebo arm was not a factor in the high placebo effect. Other serum measures (cholesterol, CRP, and LDL) did not significantly change for either group, Dr. Hershman and associates said.
Key clinical point: Patients who received omega-3 fatty acid (O3-FA) capsules, as well as those who received placebo, had significant, sustained improvement in aromatase inhibitor-induced musculoskeletal pain.
Major finding: Mean observed Brief Pain Inventory worst pain scores for the O3-FA arm and the placebo arm were about 50% lower (1.74 and 1.49 points lower, respectively) than baseline scores after 12 weeks.
Data source: A multicenter, placebo controlled trial evaluating the effect of O3-FAs in 249 women with a history of breast cancer who had muscle pain and stiffness subsequent to the initiation of AI treatment.
Disclosures: Dr. Hershman reported having no disclosures. His coauthors reported ties to several industry sources.
