Minimally important difference in diffuse systemic sclerosis: results from the D-penicillamine study.

OBJECTIVE: To estimate minimally important differences (MIDs) in scores for the modified Rodnan Skin Score (mRSS) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in a clinical trial on diffuse systemic sclerosis (SSc). PARTICIPANTS AND METHODS: 134 people participated in a 2-year, double-blind, randomised clinical trial comparing efficacy of low-dose and high-dose D-penicillamine in diffuse SSc. At 6, 12, 18 and 24 months, the investigator was asked to rate the change in the patient's health since entering the study: markedly worsened, moderately worsened, slightly worsened, unchanged, slightly improved, moderately improved or markedly improved. Patients who were rated as slightly improved were defined as the minimally changed subgroup and compared with patients rated as moderately or markedly improved. RESULTS: The MID estimates for the mRSS improvement ranged from 3.2 to 5.3 (0.40-0.66 effect size) and for the HAQ-DI from 0.10 to 0.14 (0.15-0.21 effect size). Patients who were rated to improve more than slightly were found to improve by 6.9-14.2 (0.86-1.77 effect size) on the mRSS and 0.21-0.55 (0.32-0.83 effect size) on the HAQ-DI score. CONCLUSION: MID estimates are provided for improvement in the mRSS and HAQ-DI scores, which can help in interpreting clinical trials on patients with SSc and be used for sample size calculation for future clinical trials on diffuse SSc.

The Disability Index of the Health Assessment Questionnaire is a predictor and correlate of outcome in the high-dose versus low-dose penicillamine in systemic sclerosis trial.

OBJECTIVE: To explore the clinical implications of a score of > or =1.0 on the Disability Index of the Health Assessment Questionnaire (HAQ DI) at the first patient visit, and to examine the implications of improvement in HAQ DI score over 2 years in a cohort of systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma. METHODS: SSc skin and visceral involvement was assessed in 134 SSc patients with diffuse scleroderma (mean +/- SD disease duration of 10 +/- 4 months) when they entered a multicenter drug trial and again 2 years later. Mortality and the occurrence of scleroderma renal crisis were assessed for a mean +/- SD of 4.0 +/- 1.1 years. Logistic and linear regression analyses were used to examine the relationship of the baseline HAQ DI score to morbidity, mortality, and visceral involvement, as well as the relationship of changes in the HAQ DI score to changes in physical examination, laboratory, and functional variables over 2 years. RESULTS: A baseline HAQ DI score of > or =1.0 was predictive of mortality (odds ratio 3.22, 95% confidence interval 1.097-9.468) over 4 years. Multivariate linear regression demonstrated that a model which included the erythrocyte sedimentation rate at baseline (P = 0.005) and changes at 2 years in the swollen joint count (P = 0.002), total skin score (P = 0.005), and white blood cell count (P = 0.005) best explained the change in HAQ DI score over 2 years (R2 = 0.528). The HAQ DI score and total skin score at baseline were highly correlated (correlation coefficient 0.368), as were changes in the HAQ DI score and the total skin score over 2 years (correlation coefficient 0.492). Although the HAQ DI score was heavily influenced by hand dysfunction at baseline and at 2 years, improvement (reduction) in the HAQ DI score over 2 years was related to factors other than hand dysfunction. CONCLUSION: A baseline HAQ DI score of > or =1.0 predicted mortality over 4 years. Improvement in the HAQ DI score in these patients with diffuse scleroderma was associated with improvement in skin thickening, hand function, oral aperture, lung function, signs of arthritis, serum creatinine level, and the investigator's global assessment of improvement. The HAQ DI is a self-administered questionnaire that SSc patients can complete easily and rapidly and that gives the practicing physician important information about prognosis, patient status, and changes in disease course over time.

Skin thickness score as a predictor and correlate of outcome in systemic sclerosis: high-dose versus low-dose penicillamine trial.

OBJECTIVE: To study the clinical implications of a skin thickness score > or =20 at first visit and of softening of sclerodermatous skin in a cohort of systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma. METHODS: Skin and visceral involvement were assessed in 134 SSc patients with diffuse scleroderma (mean +/- SD duration of SSc 10 +/- 4 months) as they entered a multicenter drug trial and again at 2 years of followup. Advent of mortality and scleroderma renal crisis (SRC) were assessed during a followup of 4.0 +/- 1.1 years (mean +/- SD). Logistic and linear regression were used to examine the relationship of baseline skin score to morbidity, mortality, and visceral involvement and the relationship of changes in skin score to changes in physical examination, laboratory, and functional variables over 2 years. RESULTS: A baseline skin score > or =20 was associated with heart involvement at baseline (odds ratio [OR] 3.10, 95% confidence interval [95% CI] 1.25-7.70) and was predictive of mortality (OR 3.59, 95% CI 1.23-10.55) and SRC (OR 10.00, 95% CI 2.21-45.91) over 4 years. Multivariate linear regression demonstrated that a model with skin score at baseline (P = 0.0078) and changes in large joint contractures (P = 0.0072), tender joint counts (P = 0.0119), handspread (P = 0.0242), and Health Assessment Questionnaire disability index (HAQ-DI) (P = 0.0244) explained the change in skin score over 2 years (R2 = 0.567). Multivariate logistic regression demonstrated that the investigator's global assessment of improvement was best explained by a model with skin score and HAQ-DI (R2 = 0.455). CONCLUSION: A baseline skin score > or =20 was associated with heart involvement at baseline and predicted mortality and SRC over the subsequent 4 years. Improvement in skin score in these patients with diffuse cutaneous scleroderma was associated with improvement in hand function, inflammatory indices, joint contractures, arthritis signs, overall functional ability, and the examining investigator's global assessment of improvement.

Correlates of the disability index of the health assessment questionnaire: a measure of functional impairment in systemic sclerosis.

OBJECTIVE: To evaluate functional impairment in systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma at the time of entry into a trial of a therapeutic intervention (D-penicillamine). METHODS: The 20-item Disability Index of the Health Assessment Questionnaire (HAQ-DI) was administered to 134 patients as they entered a multicenter trial of high-dose versus low-dose D-penicillamine. All patients had diffuse SSc of < 18 months' duration. SSc patients who had severe organ system involvement and recent renal crisis and who were receiving prednisone > 10 mg/day were excluded from entry. Logistic regression modeling was used to examine the relationship of HAQ-DI scores to SSc skin and organ system involvement. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to estimate effects. RESULTS: The mean (+/-SD) HAQ-DI score at entry was 1.04 +/- 0.67. Fifty-three percent of patients had HAQ-DI scores > or = 1.0 (signifying moderate-to-severe functional impairment). Multivariate logistic regression demonstrated that impaired fist closure > or = 23 mm (OR 4.24, 95% CI 1.68-10.70), reduced handspread < or = 175 mm (OR 4.5, 95% CI 1.80-11.24), joint tenderness count > or = 1.0 (OR 2.93, 95% CI 1.16-7.40), age > or = 43 years (OR 2.44, 95% CI 1.01-5.95), platelet count > or = 330,000/mm3 (OR 2.30, 95% CI 0.96-5.57), and female sex (OR 2.43, 95% CI 0.77-7.73) were the most important correlates of HAQ-DI scores > or = 1.0. CONCLUSION: Increased HAQ-DI scores at baseline were correlated with reduced fist closure, reduced hand-spread, elevated platelet count, presence of tender joints, older age, and female sex. The most important contributor to functional impairment was hand dysfunction. Even within the first 18 months after SSc onset, moderate-severe functional impairment (HAQ-DI scores > or = 1.0) was frequent (53%) in this group of diffuse SSc patients. In early diffuse SSc, the self-administered HAQ-DI is therefore a valuable assessment of function that correlates with objective physical and laboratory measures of SSc disease involvement. Abnormal HAQ-DI scores may support patient claims of functional impairment, help to focus physician attention on implementing measures to reduce functional impairment, and be useful in reflecting the disease course over time.

High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis: analysis of a two-year, double-blind, randomized, controlled clinical trial.

OBJECTIVE: To test the hypothesis that systemic sclerosis (SSc) patients taking high-dose D-penicillamine (D-Pen) would have greater softening of skin, lower frequency of renal crisis, and better survival than patients taking low-dose D-Pen. METHODS: Seventeen centers enrolled 134 SSc patients with early (< or =18 months) diffuse cutaneous scleroderma into a 2-year, double-blind, randomized comparison of high-dose D-Pen (750-1,000 mg/day) versus low-dose D-Pen (125 mg every other day). All 134 patients were followed up for a mean+/-SD of 4.0+/-1.1 years to assess the frequencies of new-onset scleroderma renal crisis (SRC) and mortality. RESULTS: Sixty-eight patients completed 24 months of drug treatment. The course of the modified Rodnan skin thickness score in the 32 high-dose and the 36 low-dose D-Pen completers was not different at 24 months: the skin score dropped 4.8+/-10.3 (mean+/-SD) units in the high-dose group and 6.9+/-8.4 units in the low-dose group (P = 0.384 by t-test; favoring low-dose D-Pen) from 20.4+/-10.3 in the high-dose and 19.9+/-6.6 in the low-dose D-Pen group at study entry. The incidences of SRC and mortality were not different (P > 0.38 by Cox proportional hazards and by chi-square test) in the 66 high-dose patients (8 developed SRC and 8 died) compared with the 68 low-dose patients (10 developed SRC and 12 died). Of the 20 adverse event-related withdrawals, 80% occurred in the high-dose D-Pen group. CONCLUSION: The course of the skin score and the frequencies of SRC and mortality in the high-dose D-Pen group were not different from those in the low-dose D-Pen group. Eighty percent of the adverse event-related withdrawals occurred in the high-dose D-Pen patients. Although this study cannot answer the question of whether low-dose D-Pen is effective, it does suggest that there is no advantage to using D-Pen in doses higher than 125 every other day.

Successful combined medical and surgical treatment of a lower extremity sclerodermal ulcer.

Combined medical and surgical treatment of a chronic lower extremity ulcer in a patient with systemic scleroderma is described. Recent pharmacological advances including calcium channel blockers, meticulous surgical care, and skin grafting offer promise for more consistent wound closure in sclerodermal skin ulcerations.