Elicitation of health state utilities associated with varying severities of flares in Systemic Lupus Erythematosus

Abstract

BackgroundSystemic Lupus Erythematosus (SLE) is characterised by fluctuating periods of minimal disease activity and ‘flare’. Flare is an important outcome variable impacting the disease burden associated with SLE. The objective of this study was to obtain population-based utility values for varying severities of flare to measure the impact on health-related quality of life (HRQoL) in Australia, Canada, France, Japan, Spain and the UK.MethodsSix health states (HS) for varying severities of flare were developed based on literature, patient blogs, and interviews with patients (n = 12), rheumatologists (n = 7) and nurses (n = 2). HS were validated by independent clinical experts (n = 6) and pilot interviews (n = 10, UK). HS were evaluated using the time-trade-off (TTO) method during face-to-face interviews with a minimum representative sample (n = 100) of the general population, per-country. Visual Analog Scale (VAS) scores were obtained to validate TTO scores. TTO scores were converted into utility values.ResultsThe highest mean TTO utility scores were observed for the anchor HS (minimal disease activity) across all countries; means ranged from 0.66 in Japan to 0.82 in UK. All flare HS were associated with a disutility compared with the anchor HS (p < 0.001), means ranged across countries: mild flare HS: 0.55–0.71, moderate flare HS: 0.38–0.53, severe renal flare HS: 0.33–0.45, severe central nervous system (CNS) flare HS: 0.30–0.45 and severe generalised flare HS: 0.19–0.33. Mean VAS scores followed the same trend.ConclusionsThese results show increasing severity of flare has a detrimental impact on HRQoL. The severe generalised flare HS received the lowest mean utility score suggesting that the perceived day-to-day impact of a severe generalised flare was greater than a severe CNS or severe renal flare. This is, to the best of our knowledge, the first utility study to assess varying severities of flare in SLE across six different countries.

Cost-Effectiveness of Acthar Gel Versus Standard of Care for the Treatment of Exacerbations in Moderate-to-Severe Systemic Lupus Erythematosus

“…Lupus QoL scores were derived from the Phase 4 SLE clinical trial [ 21 ]; four domains (emotional health, fatigue, pain, and physical health) from the Lupus QoL measure were mapped to Short form-Six dimension utilities based on the method used in the literature [ 39 ]. In addition, disutility for chronic oral corticosteroid use [ 40 ], exacerbation (new flare) [ 41 ], exacerbation requiring steroid burst [ 40 ], surgery [ 42 – 44 ], organ damage [ 41 , 45 – 52 ], and health outcomes based on Lupus QoL domains (body image, burden to others, intimate relationships, and planning) [ 41 ] were also considered. Disutilities were sourced from the literature.…”

Belimumab (Benlysta)

“…Lupus is an autoimmune disease characterized by inflammatory processes that can occur in various tissues and organs of the body� 1 A common form of lupus is systemic lupus erythematosus (SLE) 2 with an estimated prevalence of about 1 in 2,000 individuals in Canada� 3,4 The age of onset is primarily between 16 and 55 years, 5 with females more commonly affected than males (9:1)� 4 The median ages at diagnosis for white females range from 37 to 50 years, in white males from 50 to 59, in Black females from 15 to 44, and in Black males from 45 to 64� 5 Kidney injury is common in SLE, with lupus nephritis (LN) occurring in about 50% of patients with SLE, 6 usually within 5 years of SLE diagnosis� 7 Kidney involvement can remain silent or asymptomatic for a significant period of time; 8 however, patients may experience fatigue, joint and muscle pain, edema, rash, and a variety of other symptoms� 9 The disease is associated with substantial morbidity 6 as serious complications include progression to end-stage renal disease (ESRD), 10 in which patients require dialysis or kidney transplant� 8 Initial treatment options for induction of class III, IV, and/or V active LN include a high-dose corticosteroid taper as well as immunosuppressive drugs such as mycophenolate mofetil (or mycophenolic acid) or cyclophosphamide� 8,11 The clinical expert consulted by CADTH for this review noted that other treatments in addition to standard of care for patients with an inadequate response to first-line induction therapy may include off-label use of rituximab, cyclosporin, or tacrolimus� The clinical expert for this review stated that in all cases of class III, IV, and/or V active LN, use of antimalarials (i�e�, hydroxychloroquine), bone protection (vitamin D, calcium, possibly antiresorptive drugs), immunizations with nonlive vaccines, and adjunct treatment with renin-angiotensin blockade and statins should be considered� Belimumab inhibits the B lymphocyte stimulator protein and thus reduces B-cell activity� 12 The IV administration is 10 mg/kg, administered over an hour, at 2-week intervals for the first 3 doses and at 4-week intervals thereafter in addition to standard of care therapy for patients with active LN� The recommended dose for subcutaneous injection, in addition to standard of care therapy, is 400 mg (two 200 mg injections) once weekly for 4 doses, then 200 mg once weekly thereafter for the treatment of adult patients with active LN�…”

“…Lupus is an autoimmune disease characterized by inflammatory processes that can occur in various tissues and organs of the body� 1 A common form of lupus is SLE, 2 with an estimated prevalence of about 1 in 2,000 individuals in Canada� 3,4 The age of onset is primarily between 16 years and 55 years, with females more commonly affected than males (9:1)� 5 Kidney involvement is common in SLE, and LN occurs in about 50% of lupus patients, 6 usually within 5 years of SLE diagnosis� 7 Kidney involvement can remain silent or asymptomatic for a significant period of time; 8 however, patients may experience fatigue, joint and muscle pain, edema, rash, and a variety of other symptoms� 9 The typical disease course of LN is characterized by episodes of flares in between periods of disease inactivity. 14 LN flares and uncontrolled disease activity between flares contribute to accumulating nephron loss and progressive decline in renal function.…”

Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort

“…9 Furthermore, flares have been associated with higher costs 10,11 and a diminished health-related quality of life. 12,13 Predictive factors for flares have not been consistently reported; for example, the association between younger age and flares has been reported by some investigators, 11,14–17 but not by others. 18–20 Antimalarial withdrawal has been associated with flares, 21 but that has not been always the case.…”