ΑΝΑΣΚΟΠΗΣΗ (YEAR IN REVIEW) Ρευματοειδής Αρθρίτιδα Χάρης Παπαγόρας Ρευματολόγος Επίκουρος Καθηγητής Ρευματολογίας Τμήμα Ιατρικής ΔΠΘ Βόλος, 1 Ιουνίου 2018

Δεν υπάρχει κάποια σύγκρουση συμφερόντων για αυτήν την ομιλία Δήλωση συμφερόντων Δεν υπάρχει κάποια σύγκρουση συμφερόντων για αυτήν την ομιλία Εκπαιδευτικές-ερευνητικές-συμβουλευτικές επιχορηγήσεις την τελευταία διετία: MSD, Roche, Abbvie, Novartis, Genesis, UCB

Early treatment [ET]: treatment ≤6months after symptom onset Late treatment [LT]: treatment >6 months after symptom onset Never treatment [NT]: no treatment In total, 160 patients (26.6%) received treatment within 6 months of symptom onset. Among these patients, 94 (58.8%) were prescribed sulfasalazine (SSZ), 45 (28.1%) were prescribed steroids, 8 (5.0%) were prescribed MTX, and 13 (8.1%) were prescribed other DMARDs. Only a small proportion of patients received biologic DMARDs during the study (7.6%), and these patients were evenly distributed between the ET group and the LT group N= 602 ασθενείς που πληρούσαν (κατά την είσοδο) τα κριτήρια ACR/EULAR 2010 Περίοδος ένταξης 1990-1994

Επιβίωση Arthritis Rheumatol. 2017 Aug;69(8):1566-1575 Within the cohort, there was little difference in the risk of death between treatment groups, after adjustment for age and sex (ET versus NT, HR 1.09 [95% CI 0.80, 1.11]; LT versus NT, HR 0.99 [95% CI 0.73, 1.33]) (Figure 1) Arthritis Rheumatol. 2017 Aug;69(8):1566-1575

Λειτουργικότητα Arthritis Rheumatol. 2017 Aug;69(8):1566-1575 Adjusted for sex and baseline anti–citrullinated protein antibodies, rheumatoid factor, smoking status, Health Assessment Questionnare disability index (HAQ DI), swollen joint count (SJC), tender joint count (TJC), and C-reactive protein (CRP) level, and for time-varying measures, including age, CRP level, SJC, TJC, and comorbidities, and weighted using inverse probability of treatment/censoring weights. A surprisingly high proportion of patients (32.1%) never received DMARDs or steroids. This reflects the fact that patients were recruited from primary and secondary care settings and followed up regardless of disease severity. If the study had been entirely based on continuing followup in secondary care, then patients with mild disease would have been discharged and contributed no follow-up information. Our study shows that patients who never received DMARD treatment did well and served as a useful group with which to compare the groups of patients who were treated either early or late. Arthritis Rheumatol. 2017 Aug;69(8):1566-1575

Δεδομένα από ΠΟΥ και τη βάση δεδομένων του ΟΗΕ για τις προοπτικές του πληθυσμού

Θνησιμότητα από ΡΑ The mean age-standardized RA mortality rate declined from 7.1 per million person-years in 1987–1989 to 3.7 per million person-years in 2009–2011, representing a 48.2% reduction (Table 1). Reductions of ≥25% were observed in 21 countries, while corresponding increases were seen only in Croatia, Israel, and Slovenia (Greece +14.2%) Despite population growth and population aging, the number of RA deaths declined from 1987 to 2001 because of a large reduction due to epidemiologic changes Συνολική μεταβολή της θνησιμότητας (προσαρμοσμένη για την ηλικία) από ΡΑ μεταξύ 1987 και 2011 στις 31 χώρες: -48,2% Ελλάδα: +14,2% Arthritis Rheumatol. 2017 Aug;69(8):1560-1565

Ετήσια θνησιμότητα από ΡΑ (προσαρμοσμένη ως προς την ηλικία) ανά εκατομμύριο πληθυσμού (1987-2011) An increase in the number of patients with RA due to population aging combined with a reduction in RA-associated mortality imply that the burden of disease will increase in coming decades, and this should be taken into consideration in policy-making by international and national health authorities. Arthritis Rheumatol. 2017 Aug;69(8):1560-1565

Ann Rheum Dis. 2018 Jan;77(1):85-91. OBJECTIVE: To investigate if, and when, patients diagnosed with rheumatoid arthritis (RA) in recent years are at increased risk of death. METHODS: Using an extensive register linkage, we designed a population-based nationwide cohort study in Sweden. Patients with new-onset RA from the Swedish Rheumatology Quality Register, and individually matched comparators from the general population were followed with respect to death, as captured by the total population register. RESULTS: 17 512 patients with new-onset RA between 1 January 1997 and 31 December 2014, and 78 847 matched general population comparator subjects were followed from RA diagnosis until death, emigration or 31 December 2015. There was a steady decrease in absolute mortality rates over calendar time, both in the RA cohort and in the general population. Although the relative risk of death in the RA cohort was not increased (HR=1.01, 95% CI 0.96 to 1.06), an excess mortality in the RA cohort was present 5 years after RA diagnosis (HR after 10 years since RA diagnosis=1.43 (95% CI 1.28 to 1.59)), across all calendar periods of RA diagnosis. Taking RA disease duration into account, there was no clear trend towards lower excess mortality for patients diagnosed more recently. CONCLUSIONS: Despite decreasing mortality rates, RA continues to be linked to an increased risk of death. Thus, despite advancements in RA management during recent years, increased efforts to prevent disease progression and comorbidity, from disease onset, are needed. Ann Rheum Dis. 2018 Jan;77(1):85-91.

Παράγοντες κινδύνου Ann Rheum Dis. 2018 Jan;77(1):85-91. Number of events (n), PYR and incidence rates (N/1000 PYR) of death in 17 512 patients with new-onset RA identified between 1997 and 2015 and in an individually matched general population comparator cohort (n=78 847). HR (RR) and 95% CI with the matching factors taken into account and adjusted for age and educational level. Ann Rheum Dis. 2018 Jan;77(1):85-91.

The relative risk of death among patients with rheumatoid arthritis (RA), overall and by calendar period of RA diagnosis compared with the general population and presented as HRs (95% CI). HRs are presented overall and by RA disease duration (<1 year, 1 to <5 years, 5 to <10 years, and ≥10 years since RA diagnosis). The distribution of causes of death changed somewhat during the study period, both for patients with RA and the general population. We note a decrease in deaths attributed to diseases of the circulatory system in both groups, and reciprocal increases in malignant neoplasms Ann Rheum Dis. 2018 Jan;77(1):85-91.

Βλ. και: Dysbiotic subgingival microbial communities in periodontally healthy patients with rheumatoid arthritis OBJECTIVE: To determine the association of anti-citrullinated antibodies (ACPA) with the ambient air pollutants fine particulate matter (PM2.5) and sulfur dioxide (SO2). METHODS: The CARTaGENE first-wave cohort includes 20,000 general population subjects from Quebec (Canada). On a sample of unselected 1586 subjects, we determined serum, ACPA and performed multivariable logistic regression, for the outcome of positive ACPA, assessing for independent effects of our air pollution variables, adjusting for age, sex, smoking, and French Canadian origin. Two models assessed distance to main industrial emitters of PM2.5, and of SO2, and two models assessed tons of SO2 and of PM2.5 annual emissions. We also assessed associations with PM2.5 regional ambient concentrations estimated with satellite imagery. RESULTS: Adjusted analyses suggested a positive association between annual industrial PM2.5 and SO2 emissions and the presence of ACPA antibodies (OR: 1.02, 95%CI 1.00-1.04 per 10t of PM2.5 and 100t of SO2). The data were also consistent with a negative association between the presence of ACPA, and distance to a major industrial emitter of both PM2.5 and SO2. We found no association with PM2.5 estimates of ambient levels. CONCLUSIONS: These analyses suggest that exposure to industrial emissions of air pollutants is related to ACPA positivity.

†,‡ p<0.05 vs FDR Key points: Among the FDR group, there was a nonsignificant trend toward greater prevalence of sputum IgA anti-CCP positivity than IgG anti-CCP positivity (16 of 67 [23.9%] versus 11 of 67 [16.4%]; P=0.13. The rates of sputum IgG anti-CCP positivity were higher than IgA anti-CCP in the RA patients (14 of 20 [70.0%] versus 8 of 20 [40.0%]; P=0.03). For serum, the FDRs more often had IgA than IgG anti-CCP (P50.11 by McNemar’s test), whereas the RA patients more often had IgG than IgA anti-CCP (P50.07 by McNemar’s test). In the sputum anti-CCP– positive FDRs, 11 of 14 (79%) had a higher ratio of IgA anti-CCP to total IgA in the sputum compared to the serum, and 9 of 10 (90%) had a higher ratio of IgG anti- CCP to total IgG in the sputum, which supports the notion that the anti-CCP was generated in the lung in the majority of these subjects. In the sputum anti-CCP– positive RA patients, 3 of 8 (38%) had a higher ratio of IgA anti-CCP to total IgA in the sputum, and 11 of 13 (85%) had a higher ratio of IgG anti-CCP to total IgG in the sputum. While FDRs are at increased risk of developing RA-related autoimmunity, it is clear that the number of FDRs demonstrating sputum ACPA positivity exceeds the number that statistically will develop classifiable RA. This suggests that local ACPA formation may be necessary but not sufficient to progress to systemic RA-related autoimmunity and eventually arthritis. †,‡ p<0.05 vs FDR

Arthritis Rheumatol. 2017 Jun;69(6):1165-1175 FDR FDR Regarding smoking, a similar, but not significant, association was seen in the RA patients Arthritis Rheumatol. 2017 Jun;69(6):1165-1175

Sputum anti-CCP and NETs in FDR No significant associations between sputum IgA or IgG anti-CCP levels and NET levels were found in RA patients Arthritis Rheumatol. 2017 Jun;69(6):1165-1175

Καπνός, άλλα εισπνεόμενα ερεθιστικά Η φλεγμονή του πνεύμονα (και άλλων βλεννογόνων;) πυροδοτεί ΝΕΤωση και παραγωγή IgA ACPA ΑΠΚ Γενετική προδιάθεση Ενεργοποιημένο Τ κύτταρο Καπνός, άλλα εισπνεόμενα ερεθιστικά Φλεγμονή πνεύμονα Β κύτταρο PADI Κιτρουλινοποίηση ACPA Κιτρουλλινωμένες πρωτεΐνες εαυτού Talking Point ACPAs are initially produced outside of the joint, and one area they may be produced is in the lungs. In people with a genetic susceptibility, like in HLA-DRB1 of the MHC class II molecule, environmental stimuli such as smoking may induce citrullination of self-proteins in the lungs.1-3 Because these people already have the SE mutation and the ability to better bind to citrullinated proteins, tolerance is broken and ACPAs are produced.4-6 From the lung, the ACPAs may ultimately end up in the joint. Η εναλλαγή σε IgG ACPA αναγκαίο βήμα προς την κλινική ΡΑ; Adapted from Catrina AE, et al. Nat Rev Rheumatol. 2014;10(11):645-653; Hajishengallis G. Nature Rev Immunol. 2015;15(1):30-44. References 1. Catrina AE, et al. Nat Rev Rheumatol. 2014;10(11):645-653. 2. Klareskog L, et al. Arthritis Rheum. 2006;54(1):38-46. 3. Rangel-Moreno J, et al. J Clin Invest. 2006;116(12):3183-3194. 4. James EA, et al. Arthritis Rheum. 2010;62(10):2009-2018 5. Hill JA, et al. J Immunol. 2003;171(2):538-541. 6. Sompayrac L, ed. How the Immune System Works. 4th ed. Hoboken, NJ: Wiley-Blackwell; 2012:112.

Κριτήρια ACR/EULAR 2010 για ΡΑ: Joint involvement refers to any swollen or tender joint on examination, which may be confirmed by imaging evidence of synovitis A 1.5T MRI was made at the most severely affected symptomatic side or at the dominant side if symptoms were equal at both sides Ενδιαφέρον είναι και το: Are MRI-detected erosions specific for RA? A large explorative cross-sectional study Ann Rheum Dis. 2018 Apr 20

Boer AC et al. Ann Rheum Dis. 2018 Apr 20 MRI χεριών & ποδιών Conclusion We found no scientific support that the use of MRI-detected synovitis is of additional benefit for the performance of the 2010 classification criteria. Αν στις μετρήσεις των αρθρώσεων για τα κριτήρια προστεθούν και οι προσβεβλημένες μόνο βάσει του MRI (Gold standard: DMARD initiation) Ευαισθησία: 62% 67% Ειδικότητα: 90 %  84% Boer AC et al. Ann Rheum Dis. 2018 Apr 20

Ann Rheum Dis. 2018 Apr;77(4):515-522

Διακοπή βιολογικού Ann Rheum Dis. 2018 Apr;77(4):515-522

Μείωση βιολογικού Ann Rheum Dis. 2018 Apr;77(4):515-522 CONCLUSION: Discontinuation of bDMARDs leads to an increased risk of losing remission or LDA and radiographicprogression, while tapering doses of bDMARDs does not increase the risk of relapse (LDA) or radiographicprogression, even though there is an increased risk of losing remission. Ann Rheum Dis. 2018 Apr;77(4):515-522

Αποκλιμάκωση θεραπείας, όταν ΡΑ σε ύφεση ή LDA Βιολογικός 1 csDMARD Βιολογικός 2 csDMARD Βιολογικός 3 csDMARD Ύφεση/LDA

Διακοπή ΜΤΧ με συνέχιση TCZ σε ασθενείς με LDA Η διπλά τυφλή τυχαιοποιημένη μελέτη COMP-ACT Starting at baseline (week 0), all patients received TCZ-SC 162 mg either weekly (qw; for patients weighing ≥ 100 kg) or every 2 weeks (q2w; for patients weighing < 100 kg) and continued to receive a stable pre-baseline dose of oral MTX ≥ 15 mg/week. Patients receiving SC TCZ q2w who did not achieve Disease Activity Score 28–erythrocyte sedimentation rate (DAS28-ESR) ≤ 3.2 at week 12 could increase the dosing frequency to qw. To claim non-inferiority, the upper bound of the 2-sided 95% confidence interval (CI) for the difference in change in DAS28-ESR (TCZ mono minus TCZ + MTX) had to be < 0.6. A non-inferiority margin of 0.6 was defined based on the requirement of a ≥ 0.6-unit change in order to meet a change in the European League Against Rheumatism response criteria, as changes < 0.6 were within the measurement error of the DAS methodology. Arthritis Rheumatol. 2018 Mar 25

Non-inferiority met Μέση μεταβολή DAS28 W24W40 TCZ monoTx 0.46 (95% CI 0.22, 0.70) TCZ+MTX 0.14 (95% CI −0.11, 0.39) Adjusted difference between the groups: 0.318 (95% CI 0.045, 0.592) Non-inferiority met Diff −13.6 (−24.0, −3.3) Arthritis Rheumatol. 2018 Mar 25

Επίπτωση AEs per 100 patient-years In the randomized cohort, 2 patients in the TCZ + MTX group and none in the TCZ mono group had elevation of transaminases 3x ULN. Of the 686 patients with baseline (week 0) and post-baseline screening assay results, 10 (1.5%) developed treatment-induced anti-TCZ antibodies (all before week 24, while receiving TCZ + MTX); of these, 9 patients (1.3%) developed neutralizing anti-TCZ antibodies while receiving TCZ + MTX prior to week 24, but none were positive for the IgE isotype. No patients developed anti-TCZ antibodies after week 24. CONCLUSION: Patients with RA receiving TCZ+MTX who achieve low disease activity can discontinue MTX without significant worsening of disease activity in the 16 weeks following MTX discontinuation. Επίπτωση AEs per 100 patient-years TCZ + MTX : 308.1 [95% CI 273.0, 346.4] TCZ mono : 238.0 [95% CI 207.6, 271.6] Επίπτωση SAEs per 100 patient-years TCZ + MTX: 14.35 [7.64, 24.55)] TCZ mono : 8.65 [3.74, 17.05] Arthritis Rheumatol. 2018 Mar 25

Επιπολασμός RA-ILD: 2.2% επί της RA Διάγνωση ΡΑ 2004-2016 679 ασθενείς με RA-ILD 11722 ασθενείς με ΡΑ αντίστοιχης χρονολογίας γέννησης, φύλου και ηλικίας διάγνωσης της ΡΑ Επιπολασμός RA-ILD: 2.2% επί της RA 34% των περιπτώσεων RA-ILD διαγνώστηκαν ±1 έτος από τη διάγνωση της RA Screening for pulmonary involvement is not part of the follow-up programme for RA in Denmark, and HRCT scans are not performed systematically in asymptomatic patients. The index date was defined as the date when the patient had two diagnoses, RA and ILD, regardless of which one was assigned first. Δεν υπάρχουν πληροφορίες για κάπνισμα, υποδόρια ΜΤΧ & βιολογικό Ann Rheum Dis. 2017 Oct;76(10):1700-1706

Θνητότητα RA-ILD vs RA x2-10 φορές The high risk of death within 30 days of diagnosis, particularly among patients who had been diagnosed with ILD after or at RA diagnosis, may be due to acute exacerbations in previously undiagnosed ILD. Previous cohort studies have shown that acute exacerbation as the first manifestation of ILD is common.34 35 It is a serious complication in RA-ILD as well as in idiopathic ILD and has a very high mortality.36–38 Diagnostic delay and severe disease at the time of ILD diagnosis has been described for other ILDs,39 40 and may also contribute to the high initial mortality Stratified analysis showed that HRR for death was higher in patients who were diagnosed with RA prior to ILD Ann Rheum Dis. 2017 Oct;76(10):1700-1706

19 282 ασθενείς με 46 771p-y παρακολούθησης Έκβαση: λοίμωξη που οδήγησε σε εισαγωγή σε Νοσοκομείο, θεραπεία με iv αντιβιοτικά ή θάνατο Ann Rheum Dis. 2018 Jun;77(6):905-910

Προσαρμοσμένος σχετικός κίνδυνος ανά βιολογικό φάρμακο A sensitivity analysis limiting to new starters from 2010 found certolizumab still had a lower point estimate of serious infection rate but findings were no longer statistically significant in the fully adjusted model (HR 0.85, 95% CI 0.60 to 1.21). A large number of patients in the certolizumab pegol cohort had never previously been on a biologic. In the sensitivity analysis limiting only to individuals who had failed at least one biologic, certolizumab pegol no longer had a favourable infection rate compared with etanercept. Adjustment for age, gender, DAS25-ESR, HAQ, disease duration, smoking, seropositivity, polypharmacy and baseline steroid usage Ann Rheum Dis. 2018 Jun;77(6):905-910

Επίπτωση σοβαρών λοιμώξεων ανά σύστημα The 30-day mortality following SI was 10.4% (95% CI 9.2% to 11.6%) Ann Rheum Dis. 2018 Jun;77(6):905-910

Διάμεση παρακολούθηση (έτη) CORRONA Registry Κατηγορία Ν Διάμεση παρακολούθηση (έτη) Ύφεση 3355 2.4 LDA 3912 2.5 MHDA 5062 1.7 The index date (baseline) was defined as the second of 2 consecutive visits in which a patient had sustained remission, LDA, or MHDA. Sustained remission was defined by 2 consecutive visits in which the patient was in remission preceded by a visit where the patient was not in remission. This definition, therefore, describes patients who were newly attaining remission. Patients were defined in the sustained remission exposure category after the start of followup based on their mean disease activity level (averaged over time from the index date). Mean disease activity level was estimated as time- updating and was calculated using the area under the curve method based on the trapezoidal rule (16). This procedure allowed for small deviations in the disease activity level. For example, if a patient had CDAI values of 2.0, 1.5, and 3.2 on equally spaced consecutive visits, the patient could remain in the sustained remission category since the mean CDAI was below 2.8. Similar definitions and requirements for sustained disease activity for 2 visits were used for the sustained LDA and MHDA categories. For ease of interpretation, if a patient could have contributed person-time to both the sustained remission and sustained LDA categories, the patient was only included in the sustained remission category; this categorization resulted in 196 patients being excluded from the LDA group with total person-years of 408.5. If a patient belonged to both the sustained LDA category and the sustained MHDA category, the patient was only included in the sustained LDAcategory; this categorization resulted in 423 patients being excluded fromtheMHDAgroup with total person-years of 1,392.0. Αdjusted for age, sex, and prednisone dose The goal of attaining the lowest possible RA disease activity may lead to reduced risk for serious infections

Σοβαρές λοιμώξεις σε τέκνα γυναικών με ΡΑ που είχαν λάβει TNFi Unadjusted and adjusted odds ratios for the risk of serious infections comparing different exposure categories in PAROUS Comparison Unadjusted OR (95% CI) Adjusted* OR (95% CI) TNFi pregnancy vs non-RA 1.7 (0.9, 3.0) 1.7 (0.8, 3.7) TNFi preconception vs non-RA offspring 0.8 (0.2, 3.2) 0.9 (0.2, 3.9) TNFi pregnancy vs unexposed RA offspring 1.6 (0.9, 3.1) 1.4 (0.7, 2.8) TNFi 3rd trimester vs unex-posed RA offspring 1.6 (0.6, 4.2) 1.4 (0.5, 3.6) *Adjusted for maternal age, pre-gestational diabetes, gestational diabetes, preterm birth, and medications Κατηγορία Ν Επίπτωση ΣΛ/100p-y Non-RA 14596 2.4 (2.1, 2.7) RA- nonTNFi 2476 2.5 (1.9, 3.3) RA- preconception TNFi 133 1.9 (0.5, 7.6) RA-pregnancy TNFi 380 4.2 (2.4, 7.4) RA- 3rd trimester TNFi 156 4.2 (1.8, 10.2) The outcome of interest was serious infection occurring in the offspring. We ascertained serious infections in the offspring based on ≥1 hospitalization with infection within the first 12 months of life, with a relevant diagnostic code, as primary reason for admission. We only considered the first event if more than one was identified. When we looked at the percent of serious infections in RA offspring exposed to specific TNFi, we observed a trend toward more serious infections in RA offspring exposed to infliximab as opposed to those exposed to other TNFi (absolute risk difference 5.4%; 95% CI -1.1, 20.4) (see Table 4). However, the 95% CI for all the estimates were overlapping and particularly in the case of golimumab and certolizumab, very imprecise. The most frequent type of serious infections in RA offspring exposed to TNFi, unexposed RA offspring, and non-RA offspring was acute bronchiolitis due to respiratory syncytial virus (RSV), accounting for 36% (95% CI 14, 64), 31% (95% CI 19, 46), and 33% (95% CI 27, 38) of cases respectively in these three groups (Table 5). Among all cases of serious infection occurring in RA offspring (exposed and unexposed to TNFi), we did not identify any case of tuberculosis. Vinet E et al. Arthritis Rheumatol. 2018 May 17

Μετά προτύπωση για την ηλικία ΡΑ Γ. Πληθυσμός AIR ARTIS ATTRA BIOBADASER BSRBR-RA DANBIO GISEA ORA RABBIT RATIO REGATE Reuma. pt *Because of the type of the register these data are missing from RATIO and GISEA, 38 incident TNFi-exposed lymphoma cases (RATIO: 27, GISEA: 11) and one abatacept-exposed patient (GISEA) were for that reason excluded from the calculation of the incidence rate. Comparison within the B-NHL subtype, however, showed that DLBCL was significantly over-represented in subjects with RA compared with the general population (56% of all B-NHL in RA vs 30% in the general population; table 3); whereas CLL was significantly less frequent (16% of all B-NHL in RA vs 38% in the general population; table 3). This is the largest published RA-lymphoma cohort to date Μετά προτύπωση για την ηλικία ΡΑ Γ. Πληθυσμός Ν. Hodgkin 9.5% 10.1% B-NHL 83.8% 82.6% T-NHL 6.8% 7.3% Ann Rheum Dis. 2017 Dec;76(12):2025-2030

6,194 ασθενείς 19,406 p-y There were 2 cases of Hodgkin’s lymphoma and 17 cases of non- Hodgkin’s lymphoma. Of the 17 non- Hodgkin’s lymphomas, there were 14 B cell lymphomas, 2 T cell lymphomas, and 1 case in which the cell type was unknown.

Arthritis Care Res (Hoboken). 2018 May;70(5):685-694 The broken horizontal line represents standardized incidence ratio = 1.0, i.e., no difference in lymphoma rate versus the US general population. Arthritis Care Res (Hoboken). 2018 May;70(5):685-694

Ann Rheum Dis. 2018 Apr;77(4):510-514

In patients with RA treated with bDMARDs before first cancer, the HR for death was significantly increased; however, after adjustment for extent of disease the HR was attenuated and no longer significant. This indicates that these patients had more severe cancer disease than those not treated. The underlying explanation could be that bDMARDs induce more aggressive tumours or that extent of disease influences the choice of RA treatment after the cancer diagnosis. The observation of a stronger association after adjustment for extent of disease among patients treated both before and after first cancer speaks against the first mentioned explanation. Ann Rheum Dis. 2018 Apr;77(4):510-514

86806 ασθενείς που είχαν αποτύχει σε ≥1 βιολογικό Ακολούθως έλαβαν TCZ mono (N=771), TCZ combo (N=1773), TNFi mono (N=1404), ή TNFi combo (N=4660) Εκβάσεις: επιβίωση βιολογικού, CDAI In conclusion, our results support that TCZ mono or in combination with csDMARDs are reasonable therapeutic options in patients with inadequate response to at least one bDMARD, with similar effectiveness in terms of CDAI to the TNFi combination therapy but longer retention. Ann Rheum Dis. 2018 May 5

Επιβίωση TCZ (mono ή combo) vs TNFi (mono ή combo) Ann Rheum Dis. 2018 May 5

Αποτελεσματικότητα (mono ή combo) vs TNFi (mono ή combo) In conclusion, our results support that TCZ mono or in combination with csDMARDs are reasonable therapeutic options in patients with inadequate response to at least one bDMARD, with similar effectiveness in terms of CDAI to the TNFi combination therapy but longer retention. Ann Rheum Dis. 2018 May 5

Εβδομάδα 24 52 1146 ασθενείς 1:1:1 ACR50 Lancet 2017; 390: 457–68 24 52 Tofacitinib mono Tofacitinib + MTX 1146 ασθενείς 1:1:1 Adalimumab + MTX ACR50 Lancet 2017; 390: 457–68

Non-inferiority Lancet 2017; 390: 457–68

Data are n, n (%), or n/N (%) Data are n, n (%), or n/N (%). MACE=major adverse cardiovascular event (includes non-fatal myocardial infarction, fatal cardiovascular event, and non-fatal cerebrovascular accident). *Patients could have had more than one adverse event. †One patient died of urosepsis; one patient died of atypical pneumonia and respiratory distress syndrome associated with influenza A. Lancet 2017; 390: 457–68

Συμπεράσματα Η θεραπεία της ΡΑ τις τελευταίες 10ετίες έχει βελτιώσει τις εκβάσεις των ασθενών, αλλά υπάρχουν ακόμη περιθώρια βελτίωσης Όσο χαμηλότερη η ενεργότητα της ΡΑ, τόσο μικρότερη η επίπτωση σοβαρών λοιμώξεων Η μείωση της δοσολογίας του βιολογικού φαίνεται ότι διατηρεί το θεραπευτικό αποτέλεσμα καλύτερα από την πλήρη διακοπή του Το tofacitinib φαίνεται ότι έχει μεγαλύτερο θεραπευτικό αποτέλεσμα, όταν συνδυάζεται με ΜΤΧ, οπότε είναι συγκρίσιμο με το συνδυασμό Adalimumab+ ΜΤΧ

Ευχαριστώ