BackgroundPotential associations between targeted therapies and a new cancer in patients with an inflammatory arthritis (IA) and a history of malignant disease are a frequent concern in daily rheumatology practice. IA and/or immunomodulatory drugs might confer a specific risk of malignancy. No evidence-based framework has been proposed to guide clinicians on the benefit/risk balance when initiating or reinitiating a targeted therapy (bDMARDs/tsDMARDs) in this context.ObjectivesThis initiative aimed to develop points to consider (PTC) to assist rheumatologists.when initiating/reinitiating a targeted therapy in the context of a previous malignancy.MethodsFollowing EULAR standardised operating procedures, a task force of 2 patient representatives.and 25 experts (comprising 2 methodologists, 2 EMEUNET members, 1 oncologist.and 20 rheumatologists) first met to define the research questions for a systematic literature review concerning patients with IA and a history of cancer and other relevant information for consideration including: incidence of cancer in targeted therapy-treated patients and no history of cancer, translational research in onco-rheumatology, management with targeted therapy of immune-related adverse events of checkpoint inhibitors. In a second meeting, the task force formulated.the overarching principles and the PTC.ResultsThe group formulated 5 overarching principles and 8 PTC relevant to the initiation of targeted therapies in patients with IA and a history of cancer. Major themes included a) the need to assess.the individualized risk of cancer recurrence based on the characteristics of the patient, the cancer and the underlying disease; b) the importance of engaging with specialists caring for the cancer and.to define treatment based on a shared decision between the patient and the rheumatologist;c) the possibility to initiate without delay an appropriate targeted therapy for the treatment of.the IA in patients in remission of their cancer; d) the proposal to prefer anti-cytokine bDMARDs.over other treatment options in patients with history of solid cancer and to prefer.B cell depleting therapy in patients with a history of lymphoma; e) the proposal to use JAK inhibitors and abatacept with caution, and only in the absence of therapeutic alternatives, based on.the significant increase in cancer incidence in patients without a history of cancer, with tofacitinib compared to anti-TNF in a randomized clinical trial, and a modest but significant increase.with abatacept compared to other bDMARDs in some observational studies.ConclusionThe 2023 EULAR Points to Consider provide guidance on the management of targeted therapies.in patients with IA and a history of cancer. The research agenda highlights the need for studies.to evaluate targeted therapies other than TNF inhibitors and anti-CD20 to address the evidence gaps in this setting.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsEden Sebbag: None declared, Kim Lauper: None declared, Juan Molina Collada: None declared, Daniel Aletaha: None declared, Johan Askling: None declared, Karolina Benesova: None declared, Heidi Bertheussen: None declared, Samuel Bitoun: None declared, Ertugrul Cagri Bolek: None declared, Gerd Rüdiger Burmester: None declared, Helena Canhão: None declared, Katerina Chatzidionysiou: None declared, Jeffrey Curtis: None declared, François-Xavier Danlos: None declared, vera guimaraes: None declared, Merete Lund Hetland: None declared, Florenzo Iannone: None declared, Marie Kostine: None declared, Tue Wenzel Kragstrup: None declared, Tore K. Kvien Speakers bureau: Grünenthal, Sandoz, UCB, Consultant of: AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, UCB, Grant/research support from: AbbVie, Amgen, BMS, Galapagos, Novartis, Pfizer, UCB, Anne Regierer: None declared, Hendrik Schulze-Koops: None declared, Lucía Silva-Fernández Speakers bureau: Lilly, BMS, Abbvie, Novartis, Janssen., Consultant of: Novartis, MSD, Sanofi, Janssen, Pfizer, Zoltan Szekanecz: None declared, Maya H Buch: None declared, Axel Finckh Speakers bureau: AbbVie BMS, Pfizer Eli-Lilly Sandoz, Consultant of: AbbVie, Novartis, Pfizer, MSD, Lilly, Grant/research support from: AbbVie, BMS, Galapagos, Lilly, Pfizer, Jacques-Eric Gottenberg Consultant of: Abbvie, BMS, Galpagos, Gilead, Lily, Pfizer, Roche Chugai, Sanofi, UCB, Grant/research support from: Abbvie, BMS, Pfizer.
BackgroundThe recently presented “ORAL Surveillance Study” has suggested increased risk of serious adverse events (AEs) with tofacitinib, a JAK-inhibitor (JAKi), compared to a comparator TNF-inhibitor (TNFi). Currently, there is limited real world evidence for the tolerability and safety of JAKi (1).ObjectivesTo assess the safety of JAKi compared to other biologic agents in rheumatoid arthritis (RA) patients in a real-world population, by evaluating treatment discontinuation for AEs.MethodsPooled patient database from 16 national RA registries from across Europe, Québec (Canada), Turkey, and Israel were used. Treatment discontinuation due to AEs by treatment groups, JAKi versus (vs) TNFi and JAKi vs bDMARDs with other modes of action (OMA), were compared as an overall measure of tolerability and safety of JAKi. Standard descriptive statistics were used for baseline characteristics. We plotted unadjusted cumulative incidence, then the cause-specific Cox model was used to account for competing risks, and to obtain association between covariates and the instantaneous hazard rate for AEs. Variables listed in Table 1 were used for adjustment in the fully-adjusted cause-specific Cox model.Table 1.Baseline characteristics of the study populationJAKi1(BARI, FILGO,TOFA,UPA)OMA2(ABA, ANAK, SARI, TOCI)TNFi3(ADA, CERT, ETAN, GOL, INFL)n = 9208n = 16737n = 64533Treatment duration* (yrs)0.7 [0.2, 1.7]1.1 [0.4, 2.8]1.5 [0.5, 3.9]Age57.556.853.2Female (%)81.380.773.2Disease duration (yrs)9.913.110.7Seropositivity (%)78.775.969.8Previous b/tsDMARD (%) 034.030.859.7 120.925.924.3 216.621.710.4 3 or more28.521.55.6Concomitant GC (%)44.650.741.3Concomitant CsDMARD (%) MTX22.622.028.8 MTX + other9.59.713.1 None50.552.543.5 Other17.415.914.7CRP13.2 (24.1)13.3 (25.6)12.3 (24.1)CDAI23.7 (13.8)22.9 (13.5)22.6 (14.0)DAS 284.7 (1.5)4.7 (1.6)4.6 (1.6)HAQ1.2 (0.7)1.2 (0.7)1.1 (0.7)BMI27.1 (5.9)26.8 (5.8)26.8 (5.8)Patients with at least one Comorbidity (%)51.753.949.6csDMARDs = classical synthetic DMARDs, MTX = methotrexate, GC = glucocorticoids, CRP = C-reactive protein, CDAI = Clinical Disease Activity Index, DAS 28 = Disease Activity Score 28, HAQ = Health Assessment Questionnaire, BMI = Body Mass Index, *Treatment duration (median [IQR]) = Last visit date – start date (if treatment is ongoing), treatment stop date – treatment start date (if treatment has stopped). 1BARI (baricitinib; 44.41 %), FILGO (filgotinib; 0.23%), TOFA (tofacitinib; 49.59%), UPA (upadacitinib; 5.78%); 2ABA (abatacept; 39.96%), ANAK (anakinra; 2.64%), SARI (sarilumab; 3.14%), TOCI (tocilizumab; 52.55%); 3ADA (adalimumab; 31.00%), CERT (certolizumab; 8.33%), ETAN (etanercept; 38.83%), GOLI (golimumab; 9.36%), INFL (infliximab; 12.56%)Results90,478 treatment courses were included in the analysis (Table 1). We observed similar crude incidence rate of treatment discontinuation due to AEs between JAKi and TNFi, but less in JAKi vs OMA (Figure 1). The fully adjusted hazard rate of treatment stop for AEs was also similar in JAKi vs TNFi (HR = 1.02 (95% CI 0.92 – 1.13)), and in JAKi vs OMA (HR= 1.08 (95% CI 0.97 – 1.20)). The rate of treatment stop for AEs was higher in women (HR = 1.29 (95% CI 1.21 – 1.37)) and with an increasing number of previous b/tsDMARDs (HR = 1.50; 1.48; 1.68 for 1, 2, and 3 or more previous b/ts DMARDs, respectively).Figure 1.Comparison of cumulative incidence of treatment discontinuation for adverse events in JAKi, TNFi, and OMA groupConclusionAfter adjusting for potential confounders, the rate of treatment discontinuation for AEs was comparable between JAKi and OMA or TNFi. Treatment discontinuation for AEs comprises a wide range of AEs; future analyses will be performed to investigate specific AEs, such as cancer, serious infections or major adverse cardiovascular events.References[1]Ann Rheum Dis 2022. doi: 10.1136/annrheumdis-2021-221915.Disclosure of InterestsEric Nham: None declared, Romain Aymon: None declared, Denis Mongin: None declared, Sytske Anne Bergstra: None declared, Denis Choquette Speakers bureau: DC reports speaker or consultant fees from Abbvie, Amgen, Eli Lilly, Fresenius-Kabi,Pfizer, Novartis, Sandoz, Tevapharm, Consultant of: Stated above, Catalin Codreanu Speakers bureau: CC reports speaker/consulting fees from AbbVie, Amgen, Astra Zeneca, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Richter, Consultant of: Stated above, Ori Elkayam Consultant of: OE has received consultant and honorary fees from Pfizer, Lilly, Abbvie, Novartis, Jansen, BI, Kimme Hyrich Speakers bureau: KLH has received speaker honoraria from Abbvie, Grant/research support from: KLH has received grant income from Pfizer and BMS, Florenzo Iannone Speakers bureau: FI has received consulting/speaker’s fees from Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, SOBI, Roche and UCB, Consultant of: Stated above, Nevsun Inanc Speakers bureau: NI has received consultant and speaker/honoraria from Abbvie, Lilly, MSD, Novartis, Pfizer, Roche, Amgen, Celltrion,UCB., Consultant of: Stated above, Lianne Kearsley-Fleet: None declared, Eirik kristianslund: None declared, Tore K. Kvien Speakers bureau: TKK has received fees for speaking and/or consulting from several companies among them Pfizer, AbbVie, Lilly and Galapagos/Gilead, Consultant of: Stated above, Burkhard Leeb Speakers bureau: BFL has received speaker honoraria from Sandoz, Abbvie, Eli-Lilly, Pfizer, Roche, Grünenthal, Biogen, Celgene, Galina Lukina Speakers bureau: GVL has received speaker fees from Abbvie, Lilly, Novartis, MSD, Roche, Pfizer, Dan Nordström Consultant of: DCN has acted as consultant for AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Karel Pavelka Speakers bureau: KP has received honoraria for lectures: MSD, Pfizer, Roche, Eli Lilly, Medac, UCB, SOBI, Biogen, Sandoz, Viatris, Manuel Pombo-Suarez Speakers bureau: MPS reports advisor and speaker honoraria from Janssen, Lilly, MSD, Novartis, Sanofi, Consultant of: Stated above, Ziga Rotar Speakers bureau: ZR has received fees for speaking/consulting from several companies among them Pfizer, AbbVie, and Eli Lilly, Consultant of: Stated above, Maria Jose Santos Speakers bureau: MJS has received speaker fees from Abbvie, AstraZeneca, Lilly, Novartis and Pfizer, Delphine Courvoisier: None declared, Kim Lauper Speakers bureau: KL reports speakers fees for Pfizer, Viatris and Celltrion, Consultant of: KL reports consulting fees for Pfizer, Axel Finckh Speakers bureau: AF reports honoraria and consultancies from Pfizer, BMS, MSD, Eli-Lilly, AbbVie, Galapagos, Mylan, UCB, Viatris, Consultant of: Stated above, Grant/research support from: AF reports grants from Pfizer INC, AbbVie, Galapagos, Eli Lilly
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