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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

Least squares means (SE) from mixed-effects model of (a) FACIT–Fatigue and (b) MCD–SS scores during the blinded treatment period by cycle. FACIT–Fatigue ranges from 0 to 52, lower scores represent greater fatigue severity. MCD–SS ranges from 0 to 10, higher scores represent greater symptom severity. FACIT–Fatigue Functional Assessment of Chronic Illness Therapy–Fatigue scale, MCD–SS Multicentric Castleman’s Disease–Symptom Scale, SE standard error
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Fig2: Least squares means (SE) from mixed-effects model of (a) FACIT–Fatigue and (b) MCD–SS scores during the blinded treatment period by cycle. FACIT–Fatigue ranges from 0 to 52, lower scores represent greater fatigue severity. MCD–SS ranges from 0 to 10, higher scores represent greater symptom severity. FACIT–Fatigue Functional Assessment of Chronic Illness Therapy–Fatigue scale, MCD–SS Multicentric Castleman’s Disease–Symptom Scale, SE standard error

Mentions: Siltuximab-treated subjects reported significant and durable improvements in fatigue compared with subjects in the placebo arm on both the MCD–SS Fatigue and FACIT–Fatigue scale. These improvements in fatigue were observed at the end of Cycle 1 and continued to improve throughout the study. The mixed-effects mean scores for these assessments by cycle are shown in Fig. 2. The mean FACIT–Fatigue score, where lower values indicated greater severity, increased from 32.0 at Cycle 1 Day 1 to 38.6 at Cycle 18 Day 1 in siltuximab-treated subjects compared with a decrease from 31.1 to 26.9 over the same time period in the placebo group (Fig. 2a). The mean MCD–SS Fatigue score, where a higher value indicated greater severity, was 4.19 at Cycle 1 Day 1 compared with 2.58 at Cycle 18 Day 1 in siltuximab-treated subjects, and in the placebo group the score increased from 4.52 to 5.72 over the same time period (Fig. 2b).Fig. 2


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)

Least squares means (SE) from mixed-effects model of (a) FACIT–Fatigue and (b) MCD–SS scores during the blinded treatment period by cycle. FACIT–Fatigue ranges from 0 to 52, lower scores represent greater fatigue severity. MCD–SS ranges from 0 to 10, higher scores represent greater symptom severity. FACIT–Fatigue Functional Assessment of Chronic Illness Therapy–Fatigue scale, MCD–SS Multicentric Castleman’s Disease–Symptom Scale, SE standard error
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Least squares means (SE) from mixed-effects model of (a) FACIT–Fatigue and (b) MCD–SS scores during the blinded treatment period by cycle. FACIT–Fatigue ranges from 0 to 52, lower scores represent greater fatigue severity. MCD–SS ranges from 0 to 10, higher scores represent greater symptom severity. FACIT–Fatigue Functional Assessment of Chronic Illness Therapy–Fatigue scale, MCD–SS Multicentric Castleman’s Disease–Symptom Scale, SE standard error
Mentions: Siltuximab-treated subjects reported significant and durable improvements in fatigue compared with subjects in the placebo arm on both the MCD–SS Fatigue and FACIT–Fatigue scale. These improvements in fatigue were observed at the end of Cycle 1 and continued to improve throughout the study. The mixed-effects mean scores for these assessments by cycle are shown in Fig. 2. The mean FACIT–Fatigue score, where lower values indicated greater severity, increased from 32.0 at Cycle 1 Day 1 to 38.6 at Cycle 18 Day 1 in siltuximab-treated subjects compared with a decrease from 31.1 to 26.9 over the same time period in the placebo group (Fig. 2a). The mean MCD–SS Fatigue score, where a higher value indicated greater severity, was 4.19 at Cycle 1 Day 1 compared with 2.58 at Cycle 18 Day 1 in siltuximab-treated subjects, and in the placebo group the score increased from 4.52 to 5.72 over the same time period (Fig. 2b).Fig. 2

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