Factors associated with physicians' prescriptions for rheumatoid arthritis drugs not filled by patients.

BACKGROUND: This study estimated the extent and predictors of primary nonadherence (i.e., prescriptions made by physicians but not initiated by patients) to methotrexate and to biologics or tofacitinib in rheumatoid arthritis (RA) patients who were newly prescribed these medications. METHODS: Using administrative claims linked with electronic health records (EHRs) from multiple healthcare provider organizations in the USA, RA patients who received a new prescription for methotrexate or biologics/tofacitinib were identified from EHRs. Claims data were used to ascertain filling or administration status. A logistic regression model for predicting primary nonadherence was developed and tested in training and test samples. Predictors were selected based on clinical judgment and LASSO logistic regression. RESULTS: A total of 36.8% of patients newly prescribed methotrexate failed to initiate methotrexate within 2 months; 40.6% of patients newly prescribed biologics/tofacitinib failed to initiate within 3 months. Factors associated with methotrexate primary nonadherence included age, race, region, body mass index, count of active drug ingredients, and certain previously diagnosed and treated conditions at baseline. Factors associated with biologics/tofacitinib primary nonadherence included age, insurance, and certain previously treated conditions at baseline. The area under the receiver operating characteristic curve of the logistic regression model estimated in the training sample and applied to the independent test sample was 0.86 and 0.78 for predicting primary nonadherence to methotrexate and to biologics/tofacitinib, respectively. CONCLUSIONS: This study confirmed that failure to initiate new prescriptions for methotrexate and biologics/tofacitinib was common in RA patients. It is feasible to predict patients at high risk of primary nonadherence to methotrexate and to biologics/tofacitinib and to target such patients for early interventions to promote adherence.

Presentation of SLE in UK primary care using the Clinical Practice Research Datalink.

OBJECTIVES: To describe the presenting symptoms of SLE in primary care using the Clinical Practice Research Database (CPRD) and to calculate the time from symptom presentation to SLE diagnosis. METHODS: Incident cases of SLE were identified from the CPRD between 2000 and 2012. Presenting symptoms were identified from the medical records of cases in the 5 years before diagnosis and grouped using the British Isles Lupus Activity Group (BILAG) symptom domains. The time from the accumulation of one, two and three BILAG domains to SLE diagnosis was investigated, stratified by age at diagnosis (<30, 30-49 and ≥50 years). RESULTS: We identified 1426 incident cases (170 males and 1256 females) of SLE. The most frequently recorded symptoms and signs prior to diagnosis were musculoskeletal, mucocutaneous and neurological. The median time from first musculoskeletal symptom to SLE diagnosis was 26.4 months (IQR 9.3-43.6). There was a significant difference in the time to diagnosis (log rank p<0.01) when stratified by age and disease severity at baseline, with younger patients <30 years and those with severe disease having the shortest times and patients aged ≥50 years and those with mild disease having the longest (6.4 years (IQR 5.8-6.8)). CONCLUSIONS: The time from symptom onset to SLE diagnosis is long, especially in older patients. SLE should be considered in patients presenting with flaring or chronic musculoskeletal, mucocutaneous and neurological symptoms.

Cumulative Corticosteroid Dose Over Fifty-Two Weeks in Patients With Systemic Lupus Erythematosus: Pooled Analyses From the Phase III Belimumab Trials.

OBJECTIVE: To examine the effects of treatment with belimumab on corticosteroid dose in patients with systemic lupus erythematosus (SLE) over 52 weeks in 2 randomized, controlled trials. METHODS: Data on patients who were taking corticosteroids at baseline in the Study of Belimumab in Subjects with SLE trials were pooled post hoc to compare patients who received belimumab 10 mg/kg plus standard therapy with those who received placebo plus standard therapy. The primary end point was cumulative change from baseline in corticosteroid dose (prednisone equivalent) through week 52. Further analyses specifically examined oral corticosteroid dose. RESULTS: At baseline, 966 of 1,125 patients (86%) were receiving corticosteroids (478 belimumab 10 mg/kg and 488 placebo). Most were women (94%), their mean age was 37.1 years, mean Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index score was 9.8, and mean corticosteroid dosage was 12.5 mg/day. Over 52 weeks, there was a smaller increase in mean cumulative corticosteroid dose for the belimumab group than for the placebo group (531.2 mg versus 916.3 mg; P < 0.0001). Compared with placebo, the mean of all decreases in cumulative corticosteroid dose was higher with belimumab (P = 0.0165), and the mean of all increases was lower (P = 0.0005). More patients in the belimumab group had decreases in oral corticosteroid dose (38.5% versus 30.9%), and fewer had increases in dose (18.4% versus 30.7%), compared with placebo. Adverse events were comparable across groups. CONCLUSION: Our findings show a significantly smaller increase in cumulative corticosteroid dose over 1 year, more patients with decreases in oral corticosteroid dose, and fewer patients with increases in oral corticosteroid dose in the belimumab group compared with the placebo group. These data suggest that belimumab may be steroid sparing.

Longitudinal Treatment Patterns and Associated Outcomes in Patients With Newly Diagnosed Systemic Lupus Erythematosus.

PURPOSE: The treatment of systemic lupus erythematosus (SLE) is complex, with a wide range of drugs commonly prescribed. The aims of this study were to identify longitudinal treatment patterns in patients with incident SLE and to estimate the associations of treatment patterns with clinical and economic outcomes. METHODS: This retrospective, observational cohort study used a US managed care claims database to identify patients with newly diagnosed SLE and 4-year treatment follow-up. Patients were aged ≥ 18 years, with continuous medical and pharmacy benefits for 12 months before and 48 months after the index date (first medical claim with a diagnosis of SLE). Longitudinal treatment patterns were grouped using a k-means cluster analysis. Therapies were included in the cluster analysis if the mean number of prescriptions in each year was ≥ 0.05. Clinical and economic outcomes were compared across clusters using multivariate regression analyses. FINDINGS: Data from 1611 patients with incident SLE were analyzed (91.4% women; mean [SD] age, 44.5 [9.5] years; 56.2% managed primarily by a specialist). Hydroxychloroquine and corticosteroids were the most commonly prescribed therapies; methotrexate, azathioprine, and mycophenolate mofetil also met the criteria for inclusion in the cluster analysis. Ten treatment clusters were identified; the most common was minimally treated patients (42.8%). Hydroxychloroquine monotherapy, corticosteroid monotherapy, and corticosteroid/hydroxychloroquine combination therapy were received by 34.0%, 11.2%, and 7.8% of patients, respectively. Methotrexate or azathioprine with a corticosteroid/hydroxychloroquine were received by 4.2% of patients. Changes in therapy, except discontinuations, were rare. Compared with the minimally treated cluster, those that received corticosteroid monotherapy (mean dose, >12.0 mg/d) had poorer clinical and economic outcomes; the hydroxychloroquine-monotherapy cluster had similar or better outcomes; and patients who received a corticosteroid/hydroxychloroquine with or without methotrexate or azathioprine demonstrated outcomes that were poorer but that appeared better than those with corticosteroid monotherapy. SLE-related visits with a nonspecialist were common (~45%) and remained unchanged over time despite better clinical and economic outcomes associated with specialist visits. IMPLICATIONS: This study utilized cluster analysis, an unsupervised machine-learning method, to systematically discern treatment patterns over 4 years and to estimate outcomes associated with the identified treatment patterns. The results suggest that minimal treatment is the most common approach in patients with newly diagnosed SLE. Clinical and economic outcomes are poorest with corticosteroid monotherapy but may improve with the addition of hydroxychloroquine and/or an immunosuppressive agent. A large proportion of SLE care is provided by nonspecialists despite the potential benefits of involving a specialist.

Post-marketing experiences with belimumab in the treatment of SLE patients.

Belimumab (Benlysta) is a human recombinant monoclonal antibody that targets and inhibits soluble B-lymphocyte stimulator, also known as B-cell activating factor, a proliferation and survival factor for B cells. The published clinical trials data showed that in patients with active systemic lupus erythematosus (SLE), belimumab effectively reduced peripheral B-cell levels and improved disease activity. This article reviews the belimumab clinical trials and the post-marketing experience with belimumab in the treatment of those lupus patients with persistent active disease despite current standard of care (SOC) therapy.

Burden of systemic lupus erythematosus on employment and work productivity: data from a large cohort in the southeastern United States.

OBJECTIVE: To examine the burden of systemic lupus erythematosus (SLE) on work loss, unemployment, and work productivity impairment in an SLE cohort from the southeastern US. METHODS: We examined 689 SLE patients ages 18-64 years from the Georgians Organized Against Lupus (GOAL) cohort. GOAL is a longitudinal cohort predominantly derived from the Georgia Lupus Registry, a population-based registry established in metropolitan Atlanta. We used the Kaplan-Meier method to assess the proportion of patients who self-reported work loss since diagnosis. We compared unemployment between SLE patients and the general population from the same geographic area, calculating the standardized unemployment ratio (SUR) within demographic and disease strata. We also calculated the percentage of work productivity impairment by disease outcomes. RESULTS: Of 511 patients employed at diagnosis, 249 (49%) experienced work loss within an average disease duration of 13 years. The proportion of patients who lost their jobs since diagnosis was almost twice for African Americans than for whites. However, the SURs were similar across demographic characteristics, including race. Patients with severe disease activity and severe organ damage had the highest SUR at 4.4 and 5.6, respectively. Among those that remained employed, patients with severe fatigue, neurocognitive symptoms, and musculoskeletal symptoms had the highest impairment of work productivity. CONCLUSION: SLE imposes a substantial toll on individuals and burden on society. Major factors that negatively impact work outcomes are fatigue, disease activity, and organ damage. More effective treatments along with coping strategies at the workplace are needed to reduce the burden of SLE on work outcomes.

A longitudinal analysis of costs associated with change in disease activity in systemic lupus erythematosus.

OBJECTIVES: To estimate the economic consequences of changes in disease activity on healthcare resource utilization (HRU) and costs. METHODS: A retrospective longitudinal study of systemic lupus erythematosus (SLE) patients receiving care in a regional integrated health delivery system in the US from 01/2004 through 03/2011 was conducted using electronic health records, medical chart reviews, and claims. Eligible patients were ≥18 years old, with ≥1 rheumatologist-confirmed SLE diagnosis and ≥1 eligible rheumatology encounter. Patients were continuously enrolled ≥90 days before and ≥30 days after the encounters. Charts were manually reviewed to estimate SLEDAI scores. Average unit costs of each medical procedure, facility use, and prescription were estimated from a payer perspective (2011 USD) using a managed care claims database. HRU and costs were calculated for the 30-day period surrounding every SLEDAI score date (10 days before and 19 after). Relationships between HRU/costs and SLEDAI scores were estimated using mixed-effect models. RESULTS: Overall, 178 SLE patients were included; mean age was 50.6 years, 91% were female, and 95.5% Caucasian. Patients had a total of 1343 encounters with SLEDAI scores over an average period of 1035 days. Reductions of SLEDAI scores were associated with reductions in HRU and costs. SLEDAI score reductions of 4-points were associated with reductions of 10% HRU and 14% costs over a 30-day period; reductions of 8-points had associated reductions of 19% HRU and 26% costs; and reductions of 10-points had associated reductions of 23% HRU and 31% costs. Annualized, changes in SLEDAI scores are associated with changes of $2485 (SLEDAI score change: 10-6), $4624 (10-2), and $5579 (10-0), respectively. CONCLUSION: Reductions in disease activity were associated with substantial reductions of HRU and costs. LIMITATIONS: Only short-term effects of disease activity change were investigated, disregarding other potential benefits of low disease activity on long-term organ damage prevention or comorbidities.

Cumulative burden of oral corticosteroid adverse effects and the economic implications of corticosteroid use in patients with systemic lupus erythematosus.

BACKGROUND: Corticosteroids (CSs) are used to treat patients with systemic lupus erythematosus (SLE) and are associated with potential adverse events (AEs). However, few data are currently available on the risk of AEs in CS users in an SLE population. OBJECTIVE: To examine AEs related to CS use and costs of treating CS-related AEs in patients with SLE. METHODS: In a retrospective cohort study using claims data (study period: January 1, 2000-June 30, 2010), patients aged ≥18 years having ≥2 SLE-related (International Classification of Diseases, Ninth Revision, Clinical Modification code 710.0x) outpatient or ≥1 inpatient/emergency department claim were identified with an index diagnosis date deemed as the date of first SLE diagnosis. Receipt of CS therapy was assessed within 6 months of the index diagnosis date. Cox models were used to evaluate risk of AEs in CS users and nonusers. Associated costs were computed for AEs where risk was significantly different among the cohorts. RESULTS: Of 2717 patients with SLE, 989 received CSs and 1728 did not. Users of CSs were ~1.5 times more likely to develop chronic AEs (sleep disturbances, migraines, cataracts, hypertension, and type 2 diabetes mellitus) and ~2 times more likely to develop acute AEs (pneumonia, herpes zoster, fungal infections, and nausea/vomiting) compared with CS nonusers. The mean annual cost for managing AEs was $4607 and was highest for diabetes mellitus ($9764), hypertension ($8773), and sleep disturbances ($5599). Applying differences in 1-year event rates (CS user: 58.1%; CS nonuser: 75.1%) to cost estimates yielded an additional $784 per year per CS user to manage known CS-related AEs compared with CS nonusers. CONCLUSIONS: Although CSs are prescribed to control SLE symptoms, these results highlight potential risks and costs associated with their use, which providers/payers should consider when making treatment decisions.

Healthcare utilization and costs of systemic lupus erythematosus in Medicaid.

Objective. Healthcare utilization and costs associated with systemic lupus erythematosus (SLE) in a US Medicaid population were examined. Methods. Patients ≥ 18 years old with SLE diagnosis (ICD-9-CM 710.0x) were extracted from a large Medicaid database 2002-2009. Index date was date of the first SLE diagnosis. Patients with and without SLE were matched. All patients had a variable length of followup with a minimum of 12 months. Annualized healthcare utilization and costs associated with SLE and costs of SLE flares were assessed during the followup period. Multivariate regressions were conducted to estimate incremental healthcare utilization and costs associated with SLE. Results. A total of 14,777 SLE patients met the study criteria, and 14,262 were matched to non-SLE patients. SLE patients had significantly higher healthcare utilization per year than their matched controls. The estimated incremental annual cost associated with SLE was $10,984, with the highest increase in inpatient costs (P < 0.001). Cost per flare was $11,716 for severe flares, $562 for moderate flares, and $129 for mild flares. Annual total costs for patients with severe flares were $49,754. Conclusions. SLE patients had significantly higher healthcare resource utilization and costs than non-SLE patients. Patients with severe flares had the highest costs.

Clinical improvement and satisfaction with biologic therapy in patients with severe plaque psoriasis: results of a European cross-sectional observational study.

BACKGROUND: Efficacy of biologic therapies for psoriasis has been demonstrated in randomized trials, but effectiveness in real-world settings has yet to be fully determined. OBJECTIVE: To compare clinical improvement and treatment satisfaction with biologic versus other therapies in patients with plaque psoriasis. METHODS: European dermatologists recruited psoriasis patients into an observational study. Dermatologists reported disease severity before and after starting current therapy; dermatologists and patients reported treatment satisfaction. RESULTS: These analyses included 2151 patients: topicals, n = 453; phototherapy, n = 666; conventional systemics, n = 683; biologics, n = 349. The percentage with severe disease declined from 70% before to 15% after biologics, a significantly greater decline than other therapies: topicals, 22-10%; phototherapy, 20-11%; conventional systemics, 49-15% (all p ≤ 0.03). Significantly more patients (59%) receiving biologics were satisfied with treatment versus topicals (45%), phototherapy (34%), or conventional systemics (50%) (all p < 0.001). Significantly more dermatologists were satisfied with biologics (60%) versus topicals (35%), phototherapy (26%), or conventional systemics (42%) (all p < 0.001). CONCLUSIONS: In this study, more patients receiving biologic therapies improved from severe to moderate or mild psoriasis than patients on other treatments. More patients with plaque psoriasis and their dermatologists were satisfied with biologics than any other treatment.

The efficacy and safety of etanercept when used with as-needed adjunctive topical therapy in a randomised, double-blind study in subjects with moderate-to-severe psoriasis (the PRISTINE trial).

OBJECTIVE: To assess the efficacy and safety of two etanercept dose regimens for psoriasis treatment. METHODS: Subjects were ≥18 years old with stable moderate-to-severe plaque psoriasis. Subjects were randomised to etanercept 50 mg once weekly (QW) or 50 mg twice weekly (BIW) double-blind for 12 weeks, followed by 50 mg QW open label in all subjects through week 24. Only mild topical corticosteroids were permitted on scalp, axillae and groin for first 12 weeks; topical medications (corticosteroids of all potencies, vitamin D analogues and combination products) were allowed as needed for second 12 weeks at physicians' discretion, consistent with "real-world" therapeutic practice. An independent ethics committee reviewed and approved the study protocol. RESULTS: At week 24, 59.9% and 78.2% in the QW/QW and BIW/QW groups achieved PASI 75 improvement. Mean percentage PASI improvement in these groups was 58.5% and 74.1% at week 12 and 70.7% and 81.3% at week 24. Although permitted from weeks 12 to 24, topical agents were used in only 27.7% and 22.6% in the QW/QW and BIW/QW groups by week 24. CONCLUSION: Both etanercept regimens were efficacious in moderate-to-severe psoriasis, although the BIW/QW regimen consistently provided higher response rates than the QW/QW regimen. More potent topical medications were used electively in <25% of subjects in each group.

Application of composite disease activity scores in psoriatic arthritis to the PRESTA data set.

OBJECTIVE: This study aimed to compare the performances of the Modified Composite Psoriatic Disease Activity Index (mCPDAI) and the Disease Activity index for PSoriatic Arthritis (DAPSA) in an interventional study of etanercept in psoriatic arthritis. METHODS: The components of the CPDAI and DAPSA were extracted using PRESTA (Psoriasis Randomized Etanercept STudy in subjects with psoriatic Arthritis) study data. Data for four of the five domains of the CPDAI-thus an mCPDAI-were available: joints, skin, dactylitis and enthesitis (spinal involvement was not assessed). Domains in the calculation of DAPSA were subjected to global assessment of pain, swollen and tender joint counts, and C reactive protein. SUBJECTS: were randomised to etanercept 50 mg weekly (n=373) or 50 mg twice weekly (n=379) for 12 weeks; all subjects then received etanercept 50 mg weekly for 12 weeks. The performance of the scores at baseline and on weeks 12 and 24 was compared between the two treatment regimens. RESULTS: The mCPDAI and DAPSA could distinguish response to treatment comparing baseline and 12-week or 24-week values (p<0.0001). The mCPDAI, not DAPSA, could distinguish response between the two treatment groups at 12 weeks (p=0.0492), but not at 24 weeks. All domains evaluated contributed to the data variability of the mCPDAI; the most significant were dactylitis (r=0.64) and enthesitis (r=0.60). CONCLUSION: In psoriatic arthritis with severe skin involvement, the mCPDAI was able to distinguish treatment response between the two etanercept doses. DAPSA, while demonstrating improvement in both groups over time, was unable to distinguish response between the different doses of etanercept. Further studies are needed to confirm the sensitivity of both indexes.

Comparison of two etanercept regimens for treatment of psoriasis and psoriatic arthritis: PRESTA randomised double blind multicentre trial.

OBJECTIVES: To compare the efficacy over 12 weeks of two different etanercept regimens in treating the skin manifestations of psoriasis in patients who also have psoriatic arthritis and to evaluate efficacy and safety over an additional 12 weeks of open label etanercept treatment. Design Randomised double blind multicentre outpatient study. SETTING: 98 outpatient facilities in Europe, Latin America, and the Asia Pacific region. Participants 752 patients with both psoriasis (evaluated by dermatologists) and psoriatic arthritis (evaluated by rheumatologists). INTERVENTIONS: During the blinded portion of the study, participants were randomised to receive etanercept 50 mg twice weekly (n=379) or 50 mg once weekly (n=373) for 12 weeks by subcutaneous injection. All participants then received open label etanercept 50 mg once weekly for 12 additional weeks, while remaining blinded to the regimen. MAIN OUTCOME MEASURES: The primary efficacy end point was the proportion of participants achieving "clear" or "almost clear" on the physician's global assessment of psoriasis at week 12. Secondary efficacy analyses included psoriasis area and severity index, American College of Rheumatology responses, psoriatic arthritis response criteria, and improvement in joint and tendon disease manifestations. RESULTS: At week 12, 46% (176/379) of participants receiving etanercept 50 mg twice weekly achieved a physician's global assessment of psoriasis of "clear" or "almost clear" compared with 32% (119/373) in the group treated with 50 mg once weekly (P<0.001). In contrast, an equally high percentage of participants in both groups achieved psoriatic arthritis response criteria (77% (284/371) in the twice weekly/once weekly group versus 76% (282/371) in the once weekly/once weekly group). Participants treated with 50 mg twice weekly/once weekly had greater mean reductions from baseline in the psoriasis area and severity index at week 12 compared with those who received 50 mg once weekly/once weekly (71% v 62%, P<0.001), with less difference at week 24 (78% v 74%, P<0.110). Joint and tendon disease manifestations improved from baseline in both groups to a similar extent. No new safety signals were seen in either etanercept treatment group, and no significant difference in the safety profiles was observed. CONCLUSIONS: In participants with active psoriasis and psoriatic arthritis, initial treatment of the psoriasis with etanercept 50 mg twice weekly may allow for more rapid clearance of skin lesions than with 50 mg once weekly. A regimen of 50 mg once weekly seems to be appropriate for treatment of joint and tendon rheumatic symptoms. The choice of regimen should be determined by the clinical needs of the individual patient. TRIAL REGISTRATION: Clinical trials NCT00245960.

Efficacy and safety of etanercept in children and adolescents aged > or = 8 years with severe plaque psoriasis.

Etanercept, a fully human soluble tumor necrosis factor (TNF)-alpha receptor, is approved in Europe for treatment of severe plaque psoriasis in children > or = 8 years. The efficacy and safety of etanercept for this population was evaluated in a retrospective analysis of a previous study, which included 211 children (4-17 years) with psoriasis involving > or = 10% body surface area and Psoriasis Area and Severity Index (PASI) > or = 12. In this subanalysis, subjects aged 8-17 years received once-weekly subcutaneous etanercept 0.8 mg/kg (< or = 50 mg) or placebo in double-blind fashion for 12 weeks, followed by 24 weeks of open-label etanercept. Baseline demographics and disease characteristics were similar across treatment arms (etanercept n = 95, placebo n = 97). At week 12, 54.7% subjects receiving etanercept versus 11.3% receiving placebo achieved 75% or greater improvement in PASI (PASI 75) compared with baseline (p < 0.001). PASI 50, PASI 90, and static Physician Global Assessment of psoriasis followed a similar pattern (p < 0.001). Efficacy during the open-label phase was sustained through Week 36. Exposure-adjusted rates of adverse events for etanercept were similar or lower than those for placebo. No appreciable differences were noted in the efficacy and safety profiles between the subjects aged > or = 8 years in this analysis and those in the original study population aged 4-17 years. In conclusion, etanercept provided significant, sustained improvement in disease severity and was well tolerated in children > or = 8 years with severe plaque psoriasis.