Adverse Outcomes, Healthcare Resource Utilization, and Costs Associated with Systemic Corticosteroid use Among Adults with Systemic Lupus Erythematosus in the UK.

INTRODUCTION: This analysis was conducted to assess the incidence of adverse clinical outcomes, healthcare resource use (HCRU), and the costs associated with systemic corticosteroid (SCS) use in adults with systemic lupus erythematosus (SLE) in the UK. METHODS: We identified incident SLE cases using the Clinical Practice Research Datalink GOLD, Hospital Episode Statistics-linked healthcare, and Office for National Statistics mortality databases from January 1, 2005, to June 30, 2019. Adverse clinical outcomes, HCRU, and costs were captured for patients with and without prescribed SCS. RESULTS: Of 715 patients, 301 (42%) had initiated SCS use (mean [standard deviation (SD)] 3.2 [6.0] mg/day) and 414 (58%) had no recorded SCS use post-SLE diagnosis. Cumulative incidence of any adverse clinical outcome over 10-year follow-up was 50% (SCS group) and 22% (non-SCS group), with osteoporosis diagnosis/fracture most frequently reported. SCS exposure in the past 90 days was associated with an adjusted hazard ratio of 2.41 (95% confidence interval 1.77-3.26) for any adverse clinical outcome, with increased hazard for osteoporosis diagnosis/fracture (5.26, 3.61-7.65) and myocardial infarction (4.52, 1.16-17.71). Compared to low-dose SCS (< 7.5 mg/day), patients on high-dose SCS (≥ 7.5 mg/day) had increased hazard for myocardial infarction (14.93, 2.71-82.31), heart failure (9.32, 2.45-35.43), osteoporosis diagnosis/fracture (5.14, 2.82-9.37), and type 2 diabetes (4.02 1.13-14.27). Each additional year of SCS use was associated with increased hazard for any adverse clinical outcome (1.15, 1.05-1.27). HCRU and costs were greater for SCS users than non-SCS users. CONCLUSIONS: Among patients with SLE, there is a higher burden of adverse clinical outcomes and greater HCRU in SCS versus non-SCS users.

Healthcare Resource Use and Costs Associated with Organ Damage in Newly Diagnosed Adults with Systemic Lupus Erythematosus in the UK.

INTRODUCTION: This analysis compared healthcare resource use (HCRU) and costs associated with incident organ damage in a cohort of adult patients with systemic lupus erythematosus (SLE). METHODS: Incident SLE cases were identified (Clinical Practice Research Datalink [CPRD] and Hospital Episode Statistics-linked healthcare databases; January 1, 2005-June 30, 2019). Annual incidence of 13 organ damage domains was calculated from SLE diagnosis through follow-up. Annualized HCRU and costs were compared between organ damage and non-organ damage patient groups using generalized estimating equations. RESULTS: A total of 936 patients met the inclusion criteria for SLE. Mean age was 48.0 (standard deviation [SD] 15.7) years and 88% were female. Over a median follow-up period of 4.3 (interquartile range [IQR] 1.9-7.0) years, 59% (315/533) had evidence of post-SLE diagnosis incident organ damage (≥ 1 type), which was greatest for musculoskeletal (146/819 [18%]), cardiovascular (149/842 [18%]), and skin (148/856 [17%]) domains. Patients with organ damage had greater resource use for all organ systems, excluding gonadal, versus those without it. Overall, mean (SD) annualized all-cause HCRU was greater in patients with organ damage versus those without it (inpatient, 1.0 versus 0.2; outpatient, 7.3 versus 3.5; accident and emergency, 0.5 versus 0.2 days; primary care contacts, 28.7 versus 16.5; prescription medications, 62.3 versus 22.9). Adjusted mean annualized all-cause costs were significantly greater in both post- and pre-organ damage index periods for patients with organ damage versus those without it (all P < 0.05, excluding gonadal). Overall organ damage was associated with significantly increased adjusted mean annualized per-patient cost (£4442 greater [P < 0.0001]) ranging between £2709 and £7150 greater depending on the organ damage type. CONCLUSION: Organ damage was associated with higher HCRU and healthcare costs, before and after SLE diagnosis. More effective SLE management may slow disease progression, prevent organ damage onset, improve clinical outcomes, and reduce healthcare costs.

Efficacy and safety of subcutaneous tocilizumab in rheumatoid arthritis over 1 year: a UK real-world, open-label study.

OBJECTIVE: The ACT-MOVE study assessed the real-world efficacy and safety of s.c. tocilizumab (TCZ-SC), provided as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) over 1 year, in patients with RA and an inadequate response to csDMARD therapy and/or first TNF inhibitor. METHODS: In this UK multicentre, open-label phase IIIb study, patients received TCZ-SC 162 mg once weekly for 52 weeks as monotherapy or with csDMARDs. Efficacy and safety were evaluated at baseline, weeks 2 and 4 and every 4 weeks thereafter up to week 52. RESULTS: Of 161 patients who received at least one dose of TCZ-SC, 21 (13.0%) received TCZ-SC alone and 140 (87.0%) TCZ-SC with a csDMARD(s). From baseline to week 52, there was a mean decrease in DAS28-ESR score among all patients (-3.68), and within monotherapy (-3.75) and combination therapy (-3.67) groups. The proportion of patients who achieved DAS28 clinical remission (DAS28-ESR <2.6) at week 52 was 75.4% (95% CI 66.8, 82.8). At the same time point, ≥80% of patients who remained on TCZ-SC achieved DAS28 clinical remission or had low disease activity (DAS28-ESR ≥2.6 and ≤3.2). Overall, 6.2% of patients had at least one serious adverse event (10.2/100 patient-years), and there was one death; 11.2% of patients discontinued owing to adverse events. CONCLUSION: TCZ-SC was effective and tolerated in a real-world setting over 1 year. The efficacy of TCZ-SC was similar whether given as monotherapy or with csDMARDs; its safety profile was consistent with that previously established. TRIAL REGISTRATION: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT02046603.

Tapering versus steady-state methotrexate in combination with tocilizumab for rheumatoid arthritis: a randomized, double-blind trial.

Objective: To explore whether tocilizumab + tapering MTX has comparable efficacy and safety vs tocilizumab + stable MTX in adult RA patients with inadequate response to MTX. Methods: This randomized, placebo-controlled non-inferiority study involved patients with severe active RA [28-joint DAS (DAS28) >5.1] who had initiated tocilizumab + MTX at the study start. Patients received open-label tocilizumab (8 mg/kg i.v. every 4 weeks) and open-label MTX. At week 24, patients achieving good/moderate EULAR response were randomized to group A (double-blind MTX taper) or group B (double-blind MTX maintenance); both arms continued open-label tocilizumab. Primary analysis was the proportion of patients maintaining good/moderate EULAR response from week 24 to 60. Results: The study stopped early due to low recruitment, although the predetermined non-inferiority criteria were still met; 427 patients were enrolled to the open-label phase at week 0. At week 24, EULAR good/moderate response was achieved in 272 individuals (64.4%) who were randomized, 136 in each arm (36% withdrew/were not eligible). Additionally, 45.0% achieved DAS28 ⩽3.2, 33.5% achieved remission (DAS28 <2.6) and 64.2% had a DAS28 change ⩾1.2. After week 24 randomization, the proportion of patients maintaining good/moderate EULAR response to week 60 was significantly greater for MTX taper vs stable MTX (76.5 vs 65.4%; P = 0.036), and since the lower limit of the 95% CI was >0.9, the pre-determined criteria for non-inferiority was fulfilled despite reduced recruitment. Safety analysis revealed no unexpected tocilizumab safety signals. Conclusions: Tapering MTX in patients with RA receiving tocilizumab was non-inferior to continuing stable MTX in maintaining a good/moderate EULAR response. There were no unexpected safety signals; tocilizumab and MTX therapy was generally well tolerated in both groups. Trial registration number: EudraCT 2011-005260-20.

The efficacy of biologic agents in patients with rheumatoid arthritis and an inadequate response to tumour necrosis factor inhibitors: a systematic review.

OBJECTIVE: To assess the relative efficacy of subsequent biologic therapies in patients with RA who have had an inadequate response to prior therapy with a TNF-α inhibitor. METHODS: A systematic review was conducted using the MEDLINE, Embase and Cochrane Library databases and abstract lists from the European League Against Rheumatism, American College of Rheumatology and British Society of Rheumatology congresses. Searches covered the period from May 2009 (August 2009 for MEDLINE) to January 2011. Therapies considered were abatacept, adalimumab, etanercept, infliximab and rituximab, used at European licensed standard dose regimens. RESULTS: Four full publications and 41 congress abstracts met the criteria for inclusion. Significant improvements in RA signs and symptoms were reported for TNF inhibitors (individual agents or groups of agents, depending on the study) and for abatacept and rituximab. Rituximab was also associated with significantly improved radiographic outcomes. No head-to-head randomized controlled trials directly comparing different agents were published during the search period. Comparative data from registries and other observational studies suggest that rituximab is at least as effective as an alternative TNF inhibitor, and in some studies significantly more effective, in TNF inadequate responders. CONCLUSIONS: RA patients with an inadequate response to one or more TNF inhibitors derive significant clinical benefit from subsequent therapy with an alternative TNF inhibitor or with rituximab or abatacept. Prospective randomized controlled trials are needed to help physicians in the best choice of further therapy for their patients.