Clinical and Economic Benefit of Achieving Disease Control in Psoriatic Arthritis and Ankylosing Spondylitis: A Retrospective Analysis from the OM1 Registry.

BACKGROUND: There is limited evidence on the clinical and economic benefit of achieving disease control in psoriatic arthritis (PsA) and ankylosing spondylitis (AS), thus we aimed to assess the impact of disease control on healthcare resource use (HCRU) and direct medical costs among US patients with PsA or AS over 1 year. METHODS: Data were derived from the US OM1 PsA/AS registries (PsA: 1/2013-12/2020; AS: 01/2013-4/2021) and the Optum Insight Clinformatics® Data Mart to identify adult patients with PsA or AS. Two cohorts were created: with disease control and without disease control. Disease control was defined as modified Disease Activity Index for Psoriatic Arthritis (DAPSA28) ≤ 4 for PsA and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 4 for AS. Outcomes were all-cause inpatient, outpatient, and emergency department (ED) visits and associated costs over a 1-year follow-up period. Mean costs per person per year (PPPY) were assessed descriptively and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were estimated for the likelihood of HCRU by logistic regression. RESULTS: The study included 1235 PsA (with disease control: N = 217; without: N = 1018) and 581 AS patients (with disease control: N = 342; without: N = 239). Patients without disease control were more likely to have an inpatient (aOR [95% CI]; PsA: 3.0 [0.9, 10.1]; AS: 7.7 [2.3, 25.1]) or ED (PsA: 1.6 [0.6, 4.2]; AS: 3.5 [1.5, 8.3]) visit than those with disease control. Those without disease control, vs. those with disease control, had greater PPPY costs associated with inpatient (PsA: $1550 vs. $443), outpatient (PsA: $1789 vs. $1327; AS: $2498 vs. $2023), and ED (PsA: $114 vs. $57; AS: $316 vs. $50) visits. CONCLUSIONS: Findings from this study demonstrate lower disease activity among patients with PsA and AS is associated with less HCRU and lower costs over the following year.

The effect of secukinumab on patient-reported outcomes in patients with active psoriatic arthritis in a randomised phase 3 trial.

BACKGROUND: The phase 3 FUTURE 5 trial (NCT02404350) showed the clinical and radiographical efficacy of secukinumab in patients with psoriatic arthritis. This analysis aimed to assess the effect of secukinumab on patient-reported outcomes (PROs). METHODS: FUTURE 5 was a phase 3, multicentre, parallel-group randomised trial in which patients who were 18 years old or older, met the classification criteria for psoriatic arthritis at screening, and had symptoms of moderate-to-severe psoriatic arthritis for at least 6 months were randomly assigned to receive secukinumab 300 mg, 150 mg, 150 mg no loading dose (NL), or placebo weekly from baseline to week 4 and every 4 weeks thereafter. The prespecified PROs of the FUTURE 5 trial were assessed first in the overall population. We report mean changes from baseline and the proportion of patients reporting improvements equal to or more than the minimum clinically important differences (MCIDs) and scores equal to or more than the normative values for patient global assessments (PtGA) of disease activity; psoriasis and arthritis visual analogue scale (VAS) scores; pain VAS; Health Assessment Questionnaire Disability Index (HAQ-DI); 36-item Short Form Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F); and quality of life questionnaires. Patients were then stratified and assessed according to their tumour necrosis factor (TNF) inhibitor status (TNF-naive and TNF-inadequate responder [TNF-IR] populations) as a post-hoc analysis. FINDINGS: Patients in all secukinumab groups reported significant least-squares mean changes from placebo at week 16 in all PROs except SF-36 mental component summary (MCS), irrespective of TNF inhibitor use. These included PtGA (300 mg difference vs placebo -12·2 [95% CI -16·3 to -8·1], 150 mg -8·22 [-12·4 to -4·1], 150 mg NL -8·3 [-12·5 to -4·2]; all p<0·0001), pain VAS (300 mg -14·3 [-18·3 to -10·2], 150 mg -11·5 [-15·6 to -7·5], 150 mg NL -11·3 [-15·3 to -7·2]; all p<0·0001), HAQ-DI (300 mg -0·33 [-0·42 to -0·24], 150 mg -0·23 [-0·32 to -0·14], 150 mg NL -0·24 [-0·33 to -0·15]; all p<0·0001), and FACIT-F (300 mg 4·8 [3·2 to 6·4], 150 mg 4·2 [2·6 to 5·8], 150 mg NL 3·5 [1·9 to 5·1]; all p<0·0001). Similarly, the proportion of patients with improvements equal to or better than MCID at week 16 was higher in the secukinumab group compared with the placebo group for most PROs except SF-36 (MCS), regardless of TNF inhibitor use. INTERPRETATION: Secukinumab resulted in early, statistically significant, clinically meaningful, sustained improvements in PROs across all doses compared with placebo in patients with active psoriatic arthritis. These improvements were seen irrespective of previous TNF inhibitor use, in a post-hoc analysis. These results indicate that secukinumab provides comprehensive improvement for patients with psoriatic arthritis, regardless of previous therapy. FUNDING: Novartis.

Clinical Utility and Cost Savings in Predicting Inadequate Response to Anti-TNF Therapies in Rheumatoid Arthritis.

INTRODUCTION: The PrismRA® test identifies rheumatoid arthritis (RA) patients who are unlikely to respond to anti-tumor necrosis factor (anti-TNF) therapies. This study evaluated the clinical and financial outcomes of incorporating PrismRA into routine clinical care of RA patients. METHODS: A decision-analytic model was created to evaluate clinical and economic outcomes in the 12-month period following first biologic treatment. Two treatment strategies were compared: (1) observed clinical decision-making based on a 175-patient cohort receiving an anti-TNF therapy as their first biologic after failure of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and (2) modeled clinical decision-making of the same population using PrismRA results to inform first-line biologic treatment choice. Modeled costs include biologic drug pharmacy, non-biologic pharmacy, and total medical costs. The odds of inadequate response to anti-TNF therapies and various components of patient care were calculated based on PrismRA results. RESULTS: Identifying predicted inadequate responders to anti-TNF therapies resulted in a modeled 38% increase in ACR50 response to first-line biologic therapies. The fraction of patients who achieved an ACR50 response to any therapy (TNFi and others) within the 12-month period was 33% higher in the PrismRA-stratified population than in the unstratified population (59 vs. 44%, respectively). When therapy prescriptions were modeled according to PrismRA results, cost savings were modeled for all financial variables: overall costs (4% decreased total, 19% decreased on ineffective treatments), total biologic drug pharmacy (4% total, 23% ineffective), non-biologic pharmacy (2% total, 19% ineffective), and medical costs (6% total, 19% ineffective). Female sex was the clinical metric that showed the greatest association with inadequate response to anti-TNF therapies (odds ratio 2.42, 95% confidence interval 1.20, 4.88). CONCLUSIONS: If PrismRA is implemented into routine clinical care as modeled, predicting which RA patients will have an inadequate response to anti-TNF therapies could save > $7 million in overall ineffective healthcare costs per 1000 patients tested and increase targeted DMARD response rates in RA.

Three-Quarters of Persons in the US Population Reporting a Clinical Diagnosis of Fibromyalgia Do Not Satisfy Fibromyalgia Criteria: The 2012 National Health Interview Survey.

OBJECTIVES: Although fibromyalgia criteria have been in effect for decades, little is known about how the fibromyalgia diagnosis is applied and understood by clinicians and patients. We used the National Health Interview Survey (NHIS) to determine the prevalence of self-reported clinician diagnosed fibromyalgia and then compared demographics, symptoms, disability and medical utilization measures of persons with a clinical diagnosis of fibromyalgia that did not meet diagnostic criteria (false-positive or prior [F/P] fibromyalgia) to persons with and without criteria-positive fibromyalgia. METHODS: The National Health Interview Survey (NHIS) collected information about both clinical diagnosis and symptoms of fibromyalgia that was appropriately weighted to represent 225,726,257 US adults. Surrogate NHIS diagnostic criteria for fibromyalgia were developed based on the level of polysymptomatic distress (PSD) as characterized in the 2011 modified American College of Rheumatology criteria (ACR) for fibromyalgia. Persons with F/P fibromyalgia were compared with persons who do not have fibromyalgia and those meeting surrogate NHIS fibromyalgia criteria. RESULTS: Of the 1.78% of persons reporting a clinical diagnosis, 73.5% did not meet NHIS fibromyalgia criteria. The prevalence of F/P fibromyalgia is 1.3%. F/P fibromyalgia is associated with a mild degree of polysymptomatic distress (NHIS PSD score 6.2) and characterized by frequent but not widespread pain and insomnia. Measures of work disability and medical utilization in F/P fibromyalgia were equal to that seen with NHIS criteria positive fibromyalgia and were 6-7x greater in F/P fibromyalgia than in non-fibromyalgia persons. F/P fibromyalgia was best predicted by being female (Odds Ratio [OR] 8.81), married (OR 3.27), and white (OR 1.96). In contrast, being a white, married woman was only modestly predictive of NHIS (criteria positive) fibromyalgia (OR 2.1). CONCLUSIONS: The majority of clinically diagnosed fibromyalgia cases in the US do not reach levels of severity necessary and sufficient for diagnosis. The clinical diagnosis of fibromyalgia is disproportionally dependent on demographic and social factors rather than the symptoms themselves. Diagnostic criteria for fibromyalgia appear to be used as a vague guide by clinicians and patients, and allow for substantial diagnostic expansion of fibromyalgia.

Limitations of clinical trials in chronic diseases: is the efficacy of methotrexate (MTX) underestimated in polyarticular psoriatic arthritis on the basis of limitations of clinical trials more than on limitations of MTX, as was seen in rheumatoid arthritis?

Clinical trials are the optimal method to establish efficacy of a drug versus placebo or another drug. Nonetheless, important limitations are seen, particularly in chronic diseases over long periods, although most are ignored. Pragmatic limitations of clinical trials include a relatively short observation period, suboptimal dosage schedules, suboptimal surrogate markers for long-term outcomes, statistically significant results which may not be clinically unimportant and vice versa. Even ideal clinical trials have intrinsic limitations, including the influence of design on results, data reported in groups which ignore individual variation, non-standard observer-dependent interpretation of a balance of efficacy and toxicity, and distortion of a "placebo effect." Limitations are seen in many clinical trials of methotrexate (MTX) in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The first MTX clinical trial in rheumatology documented excellent efficacy in PsA, but frequent adverse events in 1964, explained by intravenous doses up to 150 kg. MTX was abandoned until the 1980s for RA, while gold salts and penicillamine were termed "remission-inducing," on the basis limitations of clinical trials. In the most recent MTX in PsA (MIPA) trial, all outcomes favoured MTX, but only patient and physician global estimates met the p<0.05 criterion. A conclusion of "no evidence for MTX improving synovitis" appears explained by insufficient statistical power, wide individual variation, no subsets, low doses, and other limitations. MTX appears less efficacious in PsA than RA, but may be underestimated in PsA, similar to historical problems in RA, resulting more from limitations of clinical trials than from limitations of MTX.

The Prevalence and Characteristics of Fibromyalgia in the 2012 National Health Interview Survey.

BACKGROUND: Most knowledge of fibromyalgia comes from the clinical setting, where healthcare-seeking behavior and selection issues influence study results. The characteristics of fibromyalgia in the general population have not been studied in detail. METHODS: We developed and tested surrogate study specific criteria for fibromyalgia in rheumatology practices using variables from the US National Health Interview Survey (NHIS) and the modification (for surveys) of the 2010 American College of Rheumatology (ACR) preliminary fibromyalgia criteria. The surrogate criteria were applied to the 2012 NHIS and identified persons who satisfied criteria from symptom data. The NHIS weighted sample of 8446 persons represents 225.7 million US adults. RESULTS: Fibromyalgia was identified in 1.75% (95% CI 1.42, 2.07), or 3.94 million persons. However, 73% of identified cases self-reported a physician's diagnosis other than fibromyalgia. Identified cases had high levels of self-reported pain, non-pain symptoms, comorbidity, psychological distress, medical costs, Social Security and work disability. Caseness was associated with gender, education, ethnicity, citizenship and unhealthy behaviors. Demographics, behaviors, and comorbidity were predictive of case status. Examination of the surrogate polysymptomatic distress scale (PSD) of the 2010 ACR criteria found fibromyalgia symptoms extending through the full length of the scale. CONCLUSIONS: Persons identified with criteria-based fibromyalgia have severe symptoms, but most (73%) have not received a clinical diagnosis of fibromyalgia. The association of fibromyalgia-like symptoms over the full length of the PSD scale with physiological as well as mental stressors suggests PSD may be a universal response variable rather than one restricted to fibromyalgia.

RHEUMDOC: a one-page RHEUMatology DOCtor form with four physician global estimates for overall status, inflammation, damage, and symptoms based on neither inflammation nor damage.

A physician estimate of global status (DOCGL) is among the seven core data set measures to assess patients with rheumatoid arthritis (RA) and included in many rheumatic disease indices. In clinical trials designed to reduce in flammation, DOCGL is directed to estimate inflammatory activity. However, patients with inflammatory rheumatic diseases also may be affected by organ damage (e.g., to joints in RA, kidneys in SLE, muscles in polymyositis, and so forth.). Furthermore, fibromyalgia has been reported in 20% to 40% of patients with RA and other inflammatory rheumatic diseases, which may complicate their management. We sought to clarify a global summary of patient status by supplementing DOCGL with three additinal separate (0-10) physician global estimates for inflammation (DOCINF), damage (DOCDAM), and neither inflammation nor damage (DOCNON) (often fibromyalgia, but may be other chronic pain or somatization syndromes). In analyses of new patients with six diagnoses, mean overall DOCGL scores were highest for patients with fibromyalgia, followed by RA, spondyloarthropathy, osteoarthritis, gout, and systemic lupus erythematosus. Among the three subscales, mean DOCINF scores were highest in RA, spondyloar- thropathy, gout, and systemic lupus erythematosus; mean DOCDAM highest in osteoarthritis; and mean DOCNON in fibromyalgia. In patients with RA, mean DOCDAM and DOCNON scores indicated coexistence of clinically impor tant damage or fibromyalgia in some patients. These data indicate face validity of the three physician global estimates on subscales for inflammation, damage, and symptoms due to neither inflammation nor damage. These estimates reflect the expertise of the rheumatologist and may be helpful to interpret rheumatic disease indices.

Response to Biologic Disease-Modifying Anti-Rheumatic Drugs after Discontinuation of Anti-Tumor Necrosis Factor Alpha Agents for Rheumatoid Arthritis.

INTRODUCTION: The aim of this study was to compare the response between subsequent use of anti-tumor necrosis factor α (anti-TNF) agents and biologic disease-modifying anti-rheumatic drugs (bDMARD) with other mechanism of action (MOA) in rheumatoid arthritis (RA) patients with history of anti-TNF treatment as their first bDMARD. METHODS: A retrospective chart review was conducted at eight community-based rheumatology practices in the United States in 2012. Routine Assessment of Patient Index Data 3 (RAPID3) response was measured by comparing baseline and 6-month scores. Poor response was defined as decrease <1.8 points, follow-up score >12, or treatment discontinuation before 6 months. Percentages of patients with good and good or moderate RAPID3 response were compared for second and third biologics. Multivariate models controlled for potential confounders. RESULTS: Of 176 patients whose charts were abstracted, 122 (69.3%) received another anti-TNF agent after they discontinued their first anti-TNF. RAPID3 scores were available for 160 patients. A patient receiving a second bDMARD with another MOA had a higher good or moderate response than a patient receiving anti-TNF (53.5 vs. 30.7%, p = 0.01). In the multivariate models, treatment with another MOA was more likely to produce a good RAPID3 response [odds ratio (OR), 2.42; 95% confidence interval (CI), 1.05-5.58] or a good or moderate response (OR, 2.21; 95% CI, 1.23-3.97) than treatment with an anti-TNF. CONCLUSION: In patients who have discontinued anti-TNF agents as their first bDMARD, RAPID3 response rates are better for those receiving agents with a different MOA rather than another anti-TNF. Physicians should consider using a bDMARD with a different MOA as the next bDMARD for RA patients whose anti-TNF agent has failed.

Treat-to-target: not as simple as it appears.

Treat-to-target as a strategy for rheumatoid arthritis (RA) is now widely advocated based on strong evidence. Nonetheless, implementation of treat-to-target raises caveats, as is the case with all clinical care strategies. The target of remission or even low disease activity does not apply to all individual patients, some of whom are affected by concomitant fibromyalgia, other comorbidities, joint damage, and/or who simply prefer to maintain current status and avoid risks of more aggressive therapies. No single universal 'target' measure or index exists for all individual RA patients. An emphasis in most studies on radiographic progression, rather than physical function or mortality, as the most important outcome to document the value of treat-to-target may be inappropriate. Many reports imply that the only limitation to treating all RA patients with biological agents involves costs, ignoring effective results in most patients with methotrexate and other disease-modifying anti-rheumatic drugs (DMARDs) and adverse events associated with biological agents. Indeed, the best outcomes in reported RA clinical trials result from tight control with DMARDs, rather than from biological agents, as does better overall status of RA patients at this time compared to previous decades. Pharmacoeconomic reports may ignore that RA patients are older, less educated, and have more comorbidities than the general population, as well as critical differences in patient status according to the gross domestic product of different countries. While treating to a target of remission or low disease activity, including with biological agents, is appropriate for many patients, awareness of these concerns could improve implementation of treat-to-target for optimal care of all RA patients.

Complex measures and indices for clinical research compared with simple patient questionnaires to assess function, pain, and global estimates as rheumatology "vital signs" for usual clinical care.

Indices of multiple measures have been developed to assess and monitor patients with rheumatic diseases, as no single "gold standard" measure is available for diagnosis, prognosis, and monitoring of all individual patients. Rheumatology indices generally include 4 types of measures from a standard medical evaluation: patient history, physical examination, laboratory tests, and imaging studies. Well-characterized indices are available for rheumatoid arthritis (RA), psoriatic arthritis, systemic lupus erythematosus (SLE), ankylosing spondylitis, vasculitis, osteoarthritis, fibromyalgia, and other rheumatic diseases. These indices are complex and applied widely in clinical research, but rarely are scored in usual rheumatology patient encounters, which generally are conducted without quantitative data other than laboratory tests. Information from a patient often is as prominent in clinical decisions as information from a physical examination or laboratory tests, and is easily collected as standardized "scientific" data on patient questionnaires designed for usual clinical care, which require minimal professional effort. Patient-derived data-along with physical examination, laboratory, and imaging data-are useful rheumatology "vital signs" to assess and monitor patient status, provide documentation, and improve the quality of clinical care, in addition to their possible value for clinical research. Differences between complex measures for research and simple questionnaires designed for usual clinical care might be more widely recognized, to promote quantitative measurement in the infrastructure of usual rheumatology care.

Quantitative recording of physician clinical estimates, beyond a global estimate and formal joint count, in usual care: applying the scientific method, using a simple one-page worksheet.

Little attention has been directed to quantitation of clinical impressions and estimates of physicians. This article describes a one-page worksheet for completion by the physician at each patient visit. It includes a physician global estimate and estimate of change in status and four quantitative estimates for the degree of inflammation, degree of organ damage, and degree of fibromyalgia or somatization. An estimate of prognosis is recorded, with no therapy and with available therapies. All changes in medications are recorded. A template is available for a formal 42 joint count. The worksheet requires fewer than 15 seconds and has proven of considerable value in clinical care.

Is fatigue an inflammatory variable in rheumatoid arthritis (RA)? Analyses of fatigue in RA, osteoarthritis, and fibromyalgia.

OBJECTIVE: To investigate whether fatigue is an inflammatory (rheumatoid arthritis; RA) variable, the contributions of RA variables to fatigue, and the levels of fatigue in RA compared with osteoarthritis (OA) and fibromyalgia (FM). METHODS: We studied 2096 RA patients, 1440 with OA, and 1073 with FM in a clinical setting, and 14,607 RA, 3173 OA, and 2487 patients with FM in survey research. We partitioned variables into inflammatory and noninflammatory factors and examined variable contribution to fatigue (0-10 visual analog scale). RESULTS: Factor analysis identified Disease Activity Score-28 (DAS28) and swollen (SJC) and tender joint count (TJC) as a physician-inflammation factor, and patient global assessment, pain, Health Assessment Questionnaire, and fatigue as patient components. Fatigue demonstrated weak correlations with erythrocyte sedimentation rate (ESR; r = 0.071) and SJC (r = 0.112), weak to fair correlations with TJC (r = 0.294), physician global assessment of RA activity (r = 0.384), and DAS28 (r = 0.399), but strong correlation with patient global assessment of severity (r = 0.567). In hierarchical regression analysis, patient global explained 43.1% of DAS28 fatigue variance; when SJC, TJC, and ESR were entered, the explained variance increased to 43.7%. In reverse order, SJC, TJC, and ESR explained 9.2% of the variance, but explained variance increased to 43.7% when patient global was added. The mean clinic fatigue scores were RA 4.9, OA 4.8, FM 7.6; mean survey scores were RA 4.5, OA 4.4, FM 6.3. Adjusted for age and sex, RA and OA fatigue scores were not significantly different. CONCLUSION: Inflammatory components of the DAS28 contribute minimally to fatigue. RA and OA fatigue levels do not differ. Fatigue is not an inflammatory variable and has no unique association with RA or RA therapy.