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Evaluation of disease burden and response to treatment in adults with type 1 Gaucher disease using a validated disease severity scoring system (DS3).

ABSTRACT: GD1-DS3 is an integrated assessment of type 1 Gaucher disease (GD1) burden based on bone, hematologic and visceral domains. We investigated this disease severity scoring system (DS3) methodology for initial assessment, long-term follow-up and evaluation of treatment responses.We enrolled 133 treated adult GD1 patients. Baseline DS3 scores were calculated near the initial treatment date and patients stratified by severity as marked (DS3 6.00-19.00), moderate (DS3 3.00-5.99), mild (DS3 < 3.00). Follow-up scores were calculated annually. Minimal clinically important improvement (MCII), is defined as ?DS3 of -3.1.N370S was the most common allele (118 patients had at least one), 52 were N370S/N370S (48/52 were Ashkenazi Jews), N370S/L444P was the most common genotype among non-Jews. Median age of treatment: 45 years; median follow-up: 14 years. Baseline DS3 scores: Patients with marked disease (N = 58; median 7.84) were least likely to be N370S homozygous (19 %) and most likely to have had splenectomy (53 %), early age at diagnosis (median 18 years) and major pre-treatment bone pathology (76 %). Among patients with moderate disease (N = 53; median 4.33), 49 % were N370S/N370S, 15.1 % had splenectomy and 17 % had major bone disease. Median age at diagnosis: 32 years. No patient with mild disease (N = 22; median 2.4) had splenectomy or major skeletal disease. Median age at diagnosis: 40 years. 68 % were N370S homozygous. Response to treatment: Health-state transitions occurred primarily during the early treatment years. At Year 5, among 48 evaluable patients with marked baseline disease, eight were unchanged in severity status whereas 40 had MCII of varying degrees with 11 scored as mild. Among 42 evaluable moderate patients, none worsened, 16 remained moderate and 26 improved to mild. Among 16 evaluable mild patients, 14 remained so and 2 had DS3 scores in the low moderate range.DS3 is effective for assessing disease burden in GD1 and for monitoring response. ERT was associated with MCII in DS3 scores in patients with high severity. Nevertheless, despite better DS3 scores with treatment, GD1 patients especially those with splenectomy and pre-treatment bone pathology, continued to have bone complications.

SUBMITTER: Weinreb NJ

PROVIDER: S-EPMC4471923 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Evaluation of disease burden and response to treatment in adults with type 1 Gaucher disease using a validated disease severity scoring system (DS3).

Weinreb Neal J NJ Finegold David N DN Feingold Eleanor E Zeng Zhen Z Rosenbloom Barry E BE Shankar Suma P SP Amato Dominick D

Orphanet journal of rare diseases 20150522

<h4>Background</h4>GD1-DS3 is an integrated assessment of type 1 Gaucher disease (GD1) burden based on bone, hematologic and visceral domains. We investigated this disease severity scoring system (DS3) methodology for initial assessment, long-term follow-up and evaluation of treatment responses.<h4>Methods</h4>We enrolled 133 treated adult GD1 patients. Baseline DS3 scores were calculated near the initial treatment date and patients stratified by severity as marked (DS3 6.00-19.00), moderate (DS ...[more]

PMID: 25994334

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Project description:Gaucher disease, an autosomal recessive condition due to deficiency of lysosomal glucocerebrosidase, is a multisystemic disease, with variable age of onset, severity and progression. It is classified into subtypes delineated by the absence (type 1) or presence (type 2 and 3) of primary nervous system involvement. The ethnically diverse, largely immigrant population in South Florida has a spectrum of Gaucher disease phenotypes, creating a challenge for optimization of disease management and an opportunity to explore treatment patterns.Ninety-three records from patients with Gaucher type I in South Florida were retrieved from the International Collaborative Gaucher Group (ICGG) Registry. Individual genotypes were correlated with severity scores and success at achieving published therapeutic goals for haemoglobin concentration, platelet count, spleen volume, liver volume and amelioration of bone pain and bone crises.The majority of patients were diagnosed during the fifth decade of life. Almost two-thirds were homozygous for the N370S mutation, reflecting the large Ashkenazi Jewish population in South Florida. The majority received imiglucerase (62.8%) at various intervals. 24.5% of patients underwent splenectomy before starting enzyme replacement therapy. After a median 12 treatment years, South Florida patients matched or exceeded the ICCG 4 year therapeutic goal achievement for platelet count (85.4% vs. 79.6% success), spleen volume (93.3% vs. 78.0% success), liver volume (93.4% vs. 90.6% success), and bone crises (100% vs. 99% success). Nevertheless, fewer patients with intact spleens had sustained achievement of all 6 therapeutic goals (30.4% versus 41.4%) and only 40% of the splenectomy patients sustained achievement of 5/5 possible goals. 54.7% of the intact spleen patients continued to have bone pain vs. 29.8% in ICCG. Significantly, only 37% of the ICGG patient cohort had bone pain prior to initiation of treatment compared to 73.4% of the South Florida patients (moderate or severe pain in 59.6%).Demographic characteristics are a significant determinant of the differences in response to treatment observed in South Florida Gaucher patients compared to those described in the international population enrolled in the ICGG Gaucher Registry. Individual genotypes and ethnic background are important considerations for optimizing patient care for Gaucher disease.

Project description:ImportanceThe variation in both clinical appearance and responses to diverse treatment options emphasize the importance of an accurate, clinically relevant, yet easy-to-use scoring system in hidradenitis suppurativa.ObjectiveTo propose and provide validation data for the newly designed Severity Assessment of Hidradenitis Suppurativa score.Design, setting, and participantsWe prospectively assessed disease severity using Hurley staging and the modified Hidradenitis Suppurativa Score in 355 patients referred to Ruhr-University Bochum Department of Dermatology between March 2016 and June 2017. We also assessed disease severity via the Severity Assessment of Hidradenitis Suppurativa score.Main outcomes and measuresEvaluation and assessment of convergent validity and responsiveness to treatment of the Severity Assessment of Hidradenitis Suppurativa score.ResultsEighty-eight of the 355 patients (134 [37.7%] men and 221 [62.3%] women with a median [IQR] age of 40 [30-49] years) were classified as Hurley stage I, 221 were Hurley stage II, and 46 were Hurley stage III, with an overall median modified Hidradenitis Suppurativa Score of 31 (interquartile range [IQR], 19.3-53). The median total Severity Assessment of Hidradenitis Suppurativa score was 6 (IQR, 4-9), significantly different among the 3 Hurley groups. The median SAHS score for patients in Hurley stage I was 5 (IQR, 3-6), 6 (IQR, 5-9) for patients in Hurley stage II, and 9 (IQR, 7-12) for patients in Hurley stage III (P < .001, Kruskal-Wallis test). Correlation analysis showed a significant correlation between the modified Hidradenitis Suppurativa Score and the Severity Assessment of Hidradenitis Suppurativa score (r = 0.79, P < .001). Disease severity assessment before and after 3 months of conservative systemic treatment showed a significant correlation between the Severity Assessment of Hidradenitis Suppurativa score and modified Hidradenitis Suppurativa Score. Both the mHSS (P = .001) and the SAHS score (P < .001) significantly differed between the baseline visit (median mHSS, 33 [IQR, 24-52]; median SAHS score, 6 [IQR, 5-9]) and the 3-month visit (median mHSS, 28 [IQR, 15-43.5]; median SAHS score, 5 [IQR, 4-6.3]). The 2 patient-reported items demonstrated excellent test-retest reliability with intraclass correlation coefficient values greater than 0.8.Conclusions and relevanceOur validation data demonstrated that the Severity Assessment of Hidradenitis Suppurativa score is a disease severity instrument that significantly correlates with Hurley staging and the modified Hidradenitis Suppurativa Score, and is responsive enough to measure treatment outcome.

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Dataset Information

Evaluation of disease burden and response to treatment in adults with type 1 Gaucher disease using a validated disease severity scoring system (DS3).

Publications

Evaluation of disease burden and response to treatment in adults with type 1 Gaucher disease using a validated disease severity scoring system (DS3).

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