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Patient-reported Outcomes for Multicentric Castleman's Disease in a Randomized, Placebo-controlled Study of Siltuximab.

van Rhee F, Rothman M, Ho KF, Fleming S, Wong RS, Fosså A, Dispenzieri A, Cavet J, Munshi N, Vermeulen J, Casper C - Patient (2015)

Bottom Line: Siltuximab-treated subjects reported early improvements in symptoms compared with subjects in the placebo arm on both the MCD-SS and FACIT-Fatigue scale.Statistically significant improvements in five SF-36 domains were observed in siltuximab-treated patients, namely role physical, role emotional, vitality, bodily pain, and mental health.Siltuximab-treated patients reported significant improvements in these outcomes after treatment.

View Article: PubMed Central - PubMed

Affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA, vanrheefrits@uams.edu.

ABSTRACT

Background: Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder driven by dysregulated interleukin-6 production. MCD has a poor prognosis, and treatment is generally noncurative and aimed at symptom relief. Siltuximab is a novel, monoclonal interleukin-6 antibody recently shown to be effective in a registration clinical trial. MCD symptoms, such as fatigue, pain, and weakness, are most appropriately quantified using patient-reported outcome (PRO) measures. We assessed the effect of siltuximab on patient perception of symptoms, functional status, and wellbeing using PRO instruments.

Methods: We analyzed results of a randomized, double-blind trial comparing siltuximab 11 mg/kg every 3 weeks with placebo to treat MCD. Subjects (N = 79) completed the recently developed MCD-Symptom Scale (MCD-SS), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, and the Short Form (SF)-36 at predetermined time points throughout the treatment period. Scores were compared at baseline and over time between the treatment arms and PRO instruments.

Results: At baseline, the mean number of symptoms reported was 9.2 (standard deviation 3.76) out of 16 total, as measured by the MCD-SS. Fatigue was a key symptom across all PRO instruments. Siltuximab-treated subjects reported early improvements in symptoms compared with subjects in the placebo arm on both the MCD-SS and FACIT-Fatigue scale. Statistically significant improvements in five SF-36 domains were observed in siltuximab-treated patients, namely role physical, role emotional, vitality, bodily pain, and mental health.

Conclusions: Patients with MCD commonly report impairments in functioning, wellbeing, and fatigue at baseline. Siltuximab-treated patients reported significant improvements in these outcomes after treatment.

No MeSH data available.


Related in: MedlinePlus

Proportion of patients achieving a threshold change in MCD–SS total score during the double-blind treatment period. MCD–SS Multicentric Castleman’s Disease–Symptom Scale
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Fig5: Proportion of patients achieving a threshold change in MCD–SS total score during the double-blind treatment period. MCD–SS Multicentric Castleman’s Disease–Symptom Scale

Mentions: Using the assumption that a responder could be defined by a distribution-based criterion of 0.5 SD of the baseline value, the SD of the MCD–SS total score at baseline of 1.56 was divided by 2.0 [21]. This yielded a threshold value of approximately 0.75, which was rounded up to a more conservative threshold of 1.0. Thirteen out of 26 placebo-treated subjects (50.0 %) and 32 out of 51 siltuximab-treated subjects (62.7 %) achieved a change equal to or greater than this threshold. Figure 5 shows a cumulative distribution plot of the proportion of patients achieving a specified level of change or greater in MCD–SS total score across a range of meaningful thresholds for both treatment groups. The chart shows that changes were more pronounced in the siltuximab arm. Exploratory analyses were performed on the time to improvement for two thresholds. The 0.75-point threshold identified by the 0.5 SD approach showed an HR for time to improvement of 1.85 (p = 0.0515). A further analysis, examining the 1.0-point threshold, showed an HR of 1.373 (p = 0.3372).Fig. 5


Patient-reported Outcomes for Multicentric Castleman's Disease in a Randomized, Placebo-controlled Study of Siltuximab.

van Rhee F, Rothman M, Ho KF, Fleming S, Wong RS, Fosså A, Dispenzieri A, Cavet J, Munshi N, Vermeulen J, Casper C - Patient (2015)

Proportion of patients achieving a threshold change in MCD–SS total score during the double-blind treatment period. MCD–SS Multicentric Castleman’s Disease–Symptom Scale
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4383814&req=5

Fig5: Proportion of patients achieving a threshold change in MCD–SS total score during the double-blind treatment period. MCD–SS Multicentric Castleman’s Disease–Symptom Scale
Mentions: Using the assumption that a responder could be defined by a distribution-based criterion of 0.5 SD of the baseline value, the SD of the MCD–SS total score at baseline of 1.56 was divided by 2.0 [21]. This yielded a threshold value of approximately 0.75, which was rounded up to a more conservative threshold of 1.0. Thirteen out of 26 placebo-treated subjects (50.0 %) and 32 out of 51 siltuximab-treated subjects (62.7 %) achieved a change equal to or greater than this threshold. Figure 5 shows a cumulative distribution plot of the proportion of patients achieving a specified level of change or greater in MCD–SS total score across a range of meaningful thresholds for both treatment groups. The chart shows that changes were more pronounced in the siltuximab arm. Exploratory analyses were performed on the time to improvement for two thresholds. The 0.75-point threshold identified by the 0.5 SD approach showed an HR for time to improvement of 1.85 (p = 0.0515). A further analysis, examining the 1.0-point threshold, showed an HR of 1.373 (p = 0.3372).Fig. 5

Bottom Line: Siltuximab-treated subjects reported early improvements in symptoms compared with subjects in the placebo arm on both the MCD-SS and FACIT-Fatigue scale.Statistically significant improvements in five SF-36 domains were observed in siltuximab-treated patients, namely role physical, role emotional, vitality, bodily pain, and mental health.Siltuximab-treated patients reported significant improvements in these outcomes after treatment.

View Article: PubMed Central - PubMed

Affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA, vanrheefrits@uams.edu.

ABSTRACT

Background: Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder driven by dysregulated interleukin-6 production. MCD has a poor prognosis, and treatment is generally noncurative and aimed at symptom relief. Siltuximab is a novel, monoclonal interleukin-6 antibody recently shown to be effective in a registration clinical trial. MCD symptoms, such as fatigue, pain, and weakness, are most appropriately quantified using patient-reported outcome (PRO) measures. We assessed the effect of siltuximab on patient perception of symptoms, functional status, and wellbeing using PRO instruments.

Methods: We analyzed results of a randomized, double-blind trial comparing siltuximab 11 mg/kg every 3 weeks with placebo to treat MCD. Subjects (N = 79) completed the recently developed MCD-Symptom Scale (MCD-SS), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, and the Short Form (SF)-36 at predetermined time points throughout the treatment period. Scores were compared at baseline and over time between the treatment arms and PRO instruments.

Results: At baseline, the mean number of symptoms reported was 9.2 (standard deviation 3.76) out of 16 total, as measured by the MCD-SS. Fatigue was a key symptom across all PRO instruments. Siltuximab-treated subjects reported early improvements in symptoms compared with subjects in the placebo arm on both the MCD-SS and FACIT-Fatigue scale. Statistically significant improvements in five SF-36 domains were observed in siltuximab-treated patients, namely role physical, role emotional, vitality, bodily pain, and mental health.

Conclusions: Patients with MCD commonly report impairments in functioning, wellbeing, and fatigue at baseline. Siltuximab-treated patients reported significant improvements in these outcomes after treatment.

No MeSH data available.


Related in: MedlinePlus