Reumatoidartriidi bioloogilise ravi varasema alustamise kulutõhusus võrreldes bioloogilise ravi tavapraktikaga Eestis

Taust. Bioloogiliste haigust modifitseerivate ravimite tõhususe tõttu soosib reumatoidartriidi (RA) ravijuhendite üldine suundumus bioloogilise ravi varasemat alustamist.Eesmärk. Hinnata RA ravis kasutatavate bioloogiliste haigust modifitseerivate ravimite varasema kasutamise kulutõhusust ja eelarvemõju. Artikkel tugineb TÜ peremeditsiini ja rahvatervishoiu instituudis koostatud tervisetehnoloogiate hindamise raportile.Metoodika. Uuringus analüüsiti varem alustatud bioloogilise ravi tulemuslikkust ja kulutõhusust modelleerimise meetodil. Simulatsioonil kasutati Eesti andmeid ja nende puudumisel andmeid teaduskirjandusest. RA bioloogilise ravi tavapraktika hindamiseks analüüsiti Ida-Tallinna Keskhaigla bioloogilise ravi patsientide raviandmeid. Markovi mikrosimulatsioonimudeliga hinnati varasema bioloogilise raviga kaasnevaid tervisetulemeid ning ravi- ja töövõime kaotusest tulenevaid kulusid. Eelarvemõju analüüsis hinnati varem alustatud ravi mõju haigekassa eelarvele.Tulemused. RA ravi tavapraktikas kasutatakse enne bioloogilise ravi algust keskmiselt 3,4 (standardhälve = 0,9) haigust modifitseerivat sünteetilist ravimit (sHMR). Kui bioloogilist ravi alustatakse pärast ravikuuri 1 või 2 sHMR-iga, võidetakse eluea jooksul keskmiselt 0,1–0,2 QALYt (ingl quality adjusted life year) patsiendi kohta ja võidetud QALY maksumus on keskmiselt 67 000 eurot. Bioloogilise ravi varasema alustamisega kaasnev lisakulu haigekassale on 0,4–0,8 miljonit eurot aastas.Järeldused. RA varem alustatud bioloogilise raviga võidetud tervisetulem on pigem väike ja selle maksumus suhteliselt suur, kuid haigekassa eelarve suurenemine ei ole märkimisväärne. Seega tuleb sHMR-ide arvulise piirangu muutmisel lähtuda ravijuhenditest ja solidaarse tervisekindlustuse võimalustest.Eesti Arst 2017; 96(7):391–39

MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, double-blind RA-SCORE study

Objective To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy. Methods Patients were randomised to receive two infusions of placebo (n=63), rituximab 500 mg (n=62), or rituximab 1000 mg (n=60) intravenously on days 1 and 15. MRI scans and radiographs of the most inflamed hand and wrist were acquired at baseline, weeks 12 (MRI only), 24 and 52. The primary end point was the change in MRI erosion score from baseline at week 24. Results Patients treated with rituximab demonstrated significantly less progression in the mean MRI erosion score compared with those treated with placebo at weeks 24 (0.47, 0.18 and 1.60, respectively, p=0.003 and p=0.001 for the two rituximab doses vs placebo) and 52 (−0.30, 0.11 and 3.02, respectively; p<0.001 and p<0.001). Cartilage loss at 52 weeks was significantly reduced in the rituximab group compared with the placebo group. Other secondary end points of synovitis and osteitis improved significantly with rituximab compared with placebo as early as 12 weeks and improved further at weeks 24 and 52. Conclusions This study demonstrated that rituximab significantly reduced erosion and cartilage loss at week 24 and week 52 in MTX-inadequate responder patients with active RA, suggesting that MRI is a valuable tool for assessing inflammatory and structural damage in patients with established RA receiving rituxima

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS &gt;5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p&lt;0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P &lt; 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P &lt; 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P &lt; 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P &lt; 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P &lt; 0.001; OR(BP) = 2.4, P &lt; 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P &lt; 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P &lt; 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

MRI assessment of suppression of structural damage in patients with rheumatoid arthritis receiving rituximab: results from the randomised, placebo-controlled, double-blind RA-SCORE study.

To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy. Patients were randomised to receive two infusions of placebo (n=63), rituximab 500 mg (n=62), or rituximab 1000 mg (n=60) intravenously on days 1 and 15. MRI scans and radiographs of the most inflamed hand and wrist were acquired at baseline, weeks 12 (MRI only), 24 and 52. The primary end point was the change in MRI erosion score from baseline at week 24. Patients treated with rituximab demonstrated significantly less progression in the mean MRI erosion score compared with those treated with placebo at weeks 24 (0.47, 0.18 and 1.60, respectively, p=0.003 and p=0.001 for the two rituximab doses vs placebo) and 52 (-0.30, 0.11 and 3.02, respectively; p This study demonstrated that rituximab significantly reduced erosion and cartilage loss at week 24 and week 52 in MTX-inadequate responder patients with active RA, suggesting that MRI is a valuable tool for assessing inflammatory and structural damage in patients with established RA receiving rituximab. NCT00578305

La fatigue dans le rhumatisme psoriasique. Étude transversale portant sur 246 patients de 13 pays

International audienceObjectifs: dans le rhumatisme psoriasique (RPso), la fatigue est un aspect important pour les patients. L’objectif était d’évaluer l’ampleur de la fatigue chez les patients souffrant de RPso et les facteurs susceptibles d’expliquer une fatigue intense.Méthodes: il s’agissait d’une analyse ancillaire d’une étude transversale menée dans 13 pays sur des patients non sélectionnés atteints de RPso qui remplissaient les critères CASPAR. L’importance de la fatigue pour les patients a été évaluée par un exercice de hiérarchisation au moyen d’une échelle numérique (EN) (plage 0-10). Les facteurs pouvant être associés à une intensité de fatigue > 5/10, à savoir des variables démographiques (âge, sexe, durée de la maladie, niveau d’éducation) et des caractéristiques de la maladie (nombre d’articulations touchées, protéine réactive C, psoriasis cutané, atteinte axiale, enthésite, dactylite, dommages structuraux) ont été évalués par une analyse logistique univariée et multivariée et une analyse par régression linéaire multiple.Résultats: au total, 246 patients ont été analysés : âge moyen ± écart-type 51,2 ± 13,0 ans ; durée moyenne de la maladie 9,9 ± 10,1 ans ; score DAS 28 moyen 3,5 ± 1,3. La fatigue a été classée en deuxième position d’importance pour les patients après la douleur. Son intensité était élevée : fatigue moyenne 5,0 ± 3,0. L’intensité de fatigue > 5/10 a été bien expliquée (variance expliquée 73 %) par le psoriasis cutané (Odds Ratio 4,67 [intervalle de confiance 95 % 1,05 ; 20,72]), les articulations douloureuses (1,30 [1,01 ; 1,68]) et un faible niveau d’éducation (1,09 [1,02 ; 1,23]). Dans le modèle de régression linéaire multiple, la fatigue a été expliquée par le psoriasis cutané, les articulations douloureuses, l’enthésite, le sexe féminin et le niveau d’éducation.Conclusions: la fatigue est un problème prioritaire chez les patients atteints de RPso. La fatigue mesurée est intense chez ces patients. Les cas d’intensité > 5/10 étaient majoritairement associés à des facteurs liés à la maladie mais aussi à des variables caractéristiques des patients. La fatigue, dans le RPso, indique une étiologie multifactorielle