EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors.

BACKGROUND: Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management. METHODS: First, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed. RESULTS: The overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies. CONCLUSION: These statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.

Personalized medicine: predicting responses to therapy in patients with RA.

Personalized medicine where each patient receives the right drug and the right intensity of drug treatment for as long as needed or safe is the goal of medicine. The identification of predictors of response is the first step toward this. In rheumatoid arthritis (RA), several prediction matrices were designed to predict the risk of rapid radiological progression (RRP) in the first year of treatment, on either disease modifying anti-rheumatic drug (DMARD) monotherapy or combination therapy with prednisone or a biological agent. Both clinical markers and biomarkers of response to either anti-TNF or different mode of action biological agents, and of successful discontinuation of these agents once the treatment goal has been achieved, have been identified in different studies. Most of these markers need validation in other cohorts. Research into combining clinical markers and biomarkers of response could lead to identification of risk profiles resulting in a new step toward personalized medicine in RA.

Sustained drug-free remission in rheumatoid arthritis after DAS-driven or non-DAS-driven therapy: a comparison of two cohort studies.

OBJECTIVES: To compare the prevalence of and predictors for sustained drug-free remission in two cohorts of patients with recent-onset RA treated with DAS-driven therapy or non-DAS-driven therapy. METHODS: Sustained drug-free remission was assessed after 5 years of follow-up in 508 patients treated with DAS-driven therapy (DAS ≤ 2.4) in a randomized treatment cohort, and in 424 patients who received non-DAS-driven therapy in a prospective inception cohort. The design of the DAS-driven cohort required systematic joint assessments with DAS-driven restart of therapy. Predictors for remission were identified by univariable and multivariable logistic regression in each cohort separately and in a combined multivariate logistic regression analysis corrected for propensity scores, including a sensitivity analysis on patients receiving initial monotherapy. RESULTS: Patients in the DAS-driven cohort had more active disease at baseline, but the prevalence of sustained drug-free remission was similar after DAS-driven (9.8%) and non-DAS-driven therapy (10.6%). Among patients with ACPA, drug-free remission was more frequently achieved after DAS-driven than after non-DAS-driven therapy (5.4 vs. 2.1%, OR = 2.68, 95% CI 0.97, 7.43). Absence of ACPA and short symptom duration were independent predictors for sustained drug-free remission in both cohorts. Initial treatment choice and inclusion period were not predictive. The sensitivity analysis yielded comparable results. CONCLUSION: Retrospectively comparing a DAS-driven to a non-DAS-driven therapy cohort, the occurrence and predictors of sustained drug-free remission were similar. The DAS-driven cohort had a more unfavourable prognosis. DAS-driven therapy may improve the chance of sustained drug-free remission in ACPA-positive patients with recent-onset RA.

Cost-effectiveness targets for multi-detector row CT angiography in the work-up of patients with intermittent claudication.

PURPOSE: To determine the costs, sensitivity for detection of significant stenoses, and proportion of equivocal multi-detector row computed tomographic (CT) angiography results in the work-up of patients with intermittent claudication that would make this imaging examination cost-effective compared with gadolinium-enhanced magnetic resonance (MR) angiography. MATERIALS AND METHODS: A decision model was used to compare the societal cost-effectiveness of a new imaging modality with that of gadolinium-enhanced MR angiography. Main outcome measures were quality-adjusted life years (QALYs) and lifetime costs. By using threshold analysis of a given willingness to pay per QALY, target values for costs, sensitivity for detection of significant stenoses, and proportion of cases requiring additional work-up with intraarterial digital subtraction angiography owing to equivocal results of the new modality were determined. The base case evaluated was that of 60-year-old men with severe intermittent claudication and assumed an incremental cost-effectiveness threshold of 100,000 US dollars per QALY. RESULTS: If treatment were limited to angioplasty, a new imaging modality would be cost-effective if the costs were 300 US dollars and the sensitivity was 85%, even if up to 35% of patients needed additional work-up. When both angioplasty and bypass surgery were considered as treatment options, a new imaging modality was cost-effective if the costs were 300 US dollars, the sensitivity was higher than 94%, and 20% of patients required additional work-up. CONCLUSION: Multi-detector row CT angiography, as compared with currently used imaging modalities such as MR angiography, has the potential to be cost-effective in the evaluation of patients with intermittent claudication.

Pretreatment imaging workup for patients with intermittent claudication: a cost-effectiveness analysis.

PURPOSE: To determine the optimal imaging strategy in pretreatment workup of patients with intermittent claudication with use of noninvasive imaging modalities and intraarterial digital subtraction angiography (DSA). MATERIALS AND METHODS: A decision-analytic model that considered test characteristics such as sensitivity, complications induced by the test, implications of missing lesions, and the consequences of overtreating patients, was developed to evaluate the societal cost-effectiveness (CE) of magnetic resonance (MR) angiography, duplex ultrasonography (US), and DSA. Our main outcome measures were quality-adjusted life years (QALYs), lifetime costs (in dollars), and incremental CE ratios. The base-case analysis considered a cohort of 60-year old male patients without a history of coronary artery disease who presented with severe claudication to undergo pretreatment imaging workup. RESULTS: The range in effectiveness and lifetime costs among different diagnostic workup strategies was small (largest difference in effectiveness: 0.025 QALYs; largest difference in lifetime costs: $1,800). If treatment was limited to angioplasty in patients with suitable lesions, MR angiography had an incremental CE ratio of $35,000 per QALY compared with no diagnostic workup, and DSA had an incremental CE ratio of $471,000 per QALY compared with MR angiography. If treatment options included both angioplasty and bypass surgery, DSA had an incremental CE ratio of $179,000 per QALY compared with no diagnostic workup, and MR angiography and duplex US were less effective and more costly. CONCLUSIONS: The differences in costs and effectiveness among diagnostic imaging strategies for patients with intermittent claudication are slight and MR angiography or duplex US can replace DSA without substantial loss in effectiveness and with a slight cost reduction.

Intermittent claudication: cost-effectiveness of revascularization versus exercise therapy.

PURPOSE: To compare the costs, effectiveness, and cost-effectiveness of alternative treatment strategies for intermittent claudication. MATERIALS AND METHODS: By combining data from the literature and original patient data, a Markov decision model was developed to evaluate the societal cost-effectiveness. Patients presented with previously untreated intermittent claudication, and treatment options were exercise, percutaneous transluminal angioplasty (with stent placement, if necessary), and/or bypass surgery. Treatment strategies were defined as the initial therapy in combination with secondary treatment options should the initial therapy fail. The main outcome measures were quality-adjusted life days, expected lifetime costs (in 1995 U.S. dollars), and incremental cost-effectiveness ratios. RESULTS: Compared with an exercise program, revascularization (either angioplasty or bypass surgery) improved effectiveness by 33-61 quality-adjusted life days among patients with no history of coronary artery disease. The incremental cost-effectiveness ratio was $38,000 per quality-adjusted life year gained when angioplasty was performed whenever feasible, as compared with exercise alone, and $311,000 with additional bypass surgery. The incremental cost-effectiveness ratios were sensitive to age, history of coronary artery disease, estimated health values for no or mild claudication versus severe claudication, and revascularization costs. CONCLUSION: The results suggest that, on average, the expected gain in effectiveness achieved with bypass surgery for intermittent claudication is small compared with the costs. Angioplasty performed whenever feasible was more effective than was exercise alone, and the cost-effectiveness ratio was within the generally accepted range.