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Background: In many countries, JAK-inhibitors (JAKi) have only recently been approved as treatment for patients with rheumatoid arthritis (RA).Objectives: To evaluate the effectiveness of JAKi compared to bDMARDs in RA patients in the real-world population in an international collaboration of registers (the textquotedblleftJAK-pottextquotedblright collaboration).Methods: Patients initiating either JAKi, TNFi, IL-6i or abatacept (ABA) during a time period when JAKi were available in each country (19 registers, Table) were included. We compared the effectiveness of JAKi and bDMARDs in terms of retention using crude and adjusted survival analysis. Missing covariates were imputed using multiple imputation.Results: Among 25521 included patients, 6063 initiated a JAKi, 13879 a TNFi, 2348 ABA, and 3231 an IL-6i. Patients were on average 55 years old, with a mean disease duration 10 years, mostly seropositive (67, female (77 and with moderate disease activity at treatment initiation. The main reason of stopping treatment was ineffectiveness (49, followed by adverse events (21. Patients on JAKi were treated more often as monotherapy, had higher CRP and disease activity at baseline and had experienced more previous ts/bDMARDs. Crude median retention was 1.4 (95.2-1.5) years for JAKi, 1.6 (1.6-1.7) for TNFi, 1.5 (1.3-1.7) for IL6i and 1.1 (1.0-1.3) for ABA. After adjustment, the hazard ratio (HR) for discontinuation tended to be lower for JAKi (HR 0.86 (0.65-1.13)) compared to TNFi, but comparable for ABA (1.02 (0.94-1.10)) and IL6i (0.99 (0.88-1.10)) (Figure 1). HRs differed notably between countries (Figure 2).View this table:Table 1. RegistersConclusion: The adjusted overall drug retention of JAKi tended to be higher than for TNFi, with large variation between countries. Other measures of effectiveness, such as the evaluation of CDAI remission and low disease activity are planned to shape a more comprehensive picture of JAKi effectiveness in the real world.Disclosure of Interests: Kim Lauper: None declared, Denis Mongin: None declared, Sytske Anne Bergstra: None declared, Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Catalin Codreanu Consultant of: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Diederik De Cock: None declared, Lene Dreyer: None declared, Ori Elkayam Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Novartis, Jansen, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Nevsun Inanc: None declared, Eirik kristianslund: None declared, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Burkhard Leeb Grant/research support from: chairman of BioReg, Consultant of: AbbVie, Pfizer, Roche, Lilly, Grünenthal, Gebro,, Paid instructor for: Lilly, Biogen, Speakers bureau: Biogen, Lilly, Pfizer, Grünenthal, Astropharma,, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Dan Nordström Consultant of: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Speakers bureau: Abbvie, Celgene, Lilly, Novartis, Pfizer, Roche and UCB., Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Manuel Pombo-Suarez Consultant of: Janssen, Lilly, MSD and Sanofi., Speakers bureau: Janssen, Lilly, MSD and Sanofi., Ziga Rotar Consultant of: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Speakers bureau: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Maria Jose Santos Speakers bureau: Novartis and Pfizer, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Delphine Courvoisier: None declared, Axel Finckh Grant/research support from: Pfizer: Unrestricted research grant, Eli-Lilly: Unrestricted research grant, Consultant of: Sanofi, AB2BIO, Abbvie, Pfizer, MSD, Speakers bureau: Sanofi, Pfizer, Roche, Thermo Fisher Scientific

27 patients underwent surgical arterial reconstruction for renal artery aneurysms. Hypertension was present in 21 cases. The indication for surgery was the prevention of hemorrhagic rupture in association with hypertension. Extracorporeal surgery was performed 13 times for complex aneurysms involving several branches of the renal artery. Simple autotransplantation was performed 3 times for aneurysms located on the main renal artery. In situ surgery was performed on 11 patients (5 aneurysmectomy-arteriorrhaphies and 7 bypass operations). Results on high blood pressure showed that 10 of the 14 hypertensive patients operated by extracorporeal surgery and/or autotransplantation were cured. 1 delayed nephrectomy was performed in this group and 1 death was observed. 39 of the 46 peripheral anastomoses were patent postoperatively. All patients treated with aneurysmectomy-arteriorrhaphy were cured. In patients treated with bypass operations, 3 thromboses of the bypass and 2 failures on hypertension were observed. Aneurysmectomy and simple arterioplasty are preferred for simple renal artery aneurysms. For complex lesions involving several branches and of an intrarenal location, extracorporeal surgery and autotransplantation represent an effective treatment on hypertension and preservation of kidney function.

Extracorporeal repair of the renal artery was done in 24 patients for complex lesions extending to branches of the renal artery (9 dysplasias, 5 atheromas and 10 aneurysms). The renal artery and its branches were replaced by a hypogastric branched autograft in 20 patients and a saphenous vein graft in 4. Indications for an extracorporeal operation were hypertension, preservation of renal function against progressive deterioration and extension of the lesion to more than 2 branches of the renal artery. Of 76 peripheral anastomoses 68 were patent postoperatively. Two secondary nephrectomies were performed. Mean followup was 54 months. Hypertension was cured in 19 patients and improved in 2, while 2 failed treatment and 1 died. An extracorporeal operation may represent the best alternative for treatment of renal arterial lesions involving more than 2 branches.

BackgroundJAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers.MethodsIn this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk.ResultsWe included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA.ConclusionThe adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.

ObjectivesThe expanded therapeutic arsenal in rheumatoid arthritis (RA) raises new clinical questions. The objective of this study is to compare the effectiveness of cycling Janus kinase inhibitors (JAKi) with switching to biologic disease-modifying antirheumatic drug (bDMARD) in patients with RA after failure to the first JAKi.MethodsThis is a nested cohort study within data pooled from an international collaboration of 17 national registries (JAK-pot collaboration). Data from patients with RA with JAKi treatment failure and who were subsequently treated with either a second JAKi or with a bDMARD were prospectively collected. Differences in drug retention rates after second treatment initiation were assessed by log-rank test and Cox regression analysis adjusting for potential confounders. Change in Clinical Disease Activity Index (CDAI) over time was estimated using a linear regression model, adjusting for confounders.Results365 cycling and 1635 switching patients were studied. Cyclers were older and received a higher number of previous bDMARDs. Both strategies showed similar observed retention rates after 2 years of follow-up. However, adjusted analysis revealed that cycling was associated with higher retention (p=0.04). Among cyclers, when the first JAKi was discontinued due to an adverse event (AE), it was more likely that the second JAKi would also be stopped due to an AE. Improvement in CDAI over time was similar in both strategies.ConclusionsAfter failing the first JAKi, cycling JAKi and switching to a bDMARD appear to have similar effectiveness. Caution is advised if an AE was the reason to stop the first JAKi.