Objective. To describe clinical features associated with cancer outcomes of patients with immune checkpoint inhibitor (ICI)-associated arthritis. Methods. Observational study of patients with ICI-arthritis enrolled in a single-center registry. Arthritis phenotype and activity, medications, and cancer status were recorded at every visit. We used descriptive statistic, and Kaplan-Meier curves using two-sided log-rank test and Cox regression analysis were used to identify factors associated with cancer progression-free survival (PFS). Results. Forty-two patients with ICI-arthritis were followed for a median (interquartile range [IQR]) of 7.4 (1.7, 14.7) months. Fifty-seven percent were female, 33% had melanoma, and 69% received anti-programmed death ligand 1 monotherapy. Median time from ICI initiation to arthritis onset was 2.8 (0.8, 11.2) months. Sixty-two percent had a rheumatoid arthritis (RA)-like small-joint presentation; 27% of all patients were rheumatoid factor and/or cyclic citrullinated peptide positive. Median (IQR) Clinical Disease Activity Index (CDAI) on presentation was 15 (8, 24); 62% required systemic glucocorticoids, 55% required disease-modifying antirheumatic drugs (DMARDs), and 69% had ongoing arthritis at 6 months. Arthritis led to ICI discontinuation in five patients. In univariate analysis, baseline CDAI, DMARD use, earlier arthritis onset, and longer duration of follow-up were associated with shorter PFS. In multivariable Cox regression analysis controlling for DMARD use and time to arthritis onset, CDAI was a significant predictor of cancer progression (hazard ratio 1.09, 95% confidence interval [CI] 1.00-1.19, P = 0.05) Conclusion. ICI-arthritis most commonly presents with an RA-like phenotype. High disease activity, as measured by CDAI, may portend cancer progression.

1 JEL classifi cation codes: M10, M11, M14. M anagers and policy makers should consider using organizational foresight and twelve success factors in their attempts to improve the impact of foresight project results and steer organizational change.

BackgroundImmune checkpoint inhibitors (CI) have revolutionized cancer management, but can also cause immune-related adverse events. Five percent of CI-treated patients develop inflammatory arthritis, but it is poorly defined phenotypically and immunologically.ObjectivesTo characterize phenotypes of CI-associated arthritis, and compare cytokine levels in these patients to rheumatoid arthritis (RA) and osteoarthritis (OA) controls.MethodsPatients referred for CI-associated arthralgia or arthritis were prospectively enrolled in an institutional registry. Serum was collected when patients underwent phlebotomy for a clinical indication. We used a Luminex Human Magnetic Assay to measure levels of IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12, IL-17, IL-22, TNF, IFN-γ, PD-L1, CCL2, CXCL2, CXCL13, OSM, CCL20, GM-CSF, CXCL-11 in CI-treated patients, and in stored serum from 7 RA patients (matched for medication, age, sex, CDAI) and 4 OA patients (age, sex matched). All comparisons were planned a priori.ResultsThirty-six patients were enrolled 5/1/18-1/25/19. Median [IQR] age was 67[58-78], 18(50%) were female, 14(39%) were smokers and 13(36%) had melanoma. Twenty-two (61%) were on anti-PD1 or PD-L1 monotherapy, and the remainder were on combination CI. Phenotypes included 1. Small joint involvement in 17(47%), 2. Exclusively large joint involvement in 6(17%), 3. Arthralgia without arthritis in 9(25%), and 4. Polymyalgia rheumatica in 4(11%). In all, 7(19%) had concomitant tenosynovitis or enthesitis, mostly accompanying large joint arthritis or arthralgia (6/7). Median CDAI at entry was 11[7-23] and median ESR 29[18-44]. The majority (58%) of patients with the small joint phenotype were RF and/or CCP positive and one had erosive disease, compared to none with the large joint phenotype. ANA positivity was common (74%) and did not vary across phenotypes. Median time of symptom onset was 4[0.8-12] months after CI initiation. Median follow up was 7[3-22] months but only 5(14%) had resolution of arthritis off medication during that period. 22(61%) required CI discontinuation, 5(14%) due to arthritis. 29(81%) required steroids including 15(42%) who required >20mg prednisone. 19(53%) required a synthetic DMARD and 5(14%) required a biologic DMARD. Of 33 patients with known cancer status, 15(45%) had a complete response, 5(15%) a partial response, 5(15%) “stable” disease, 6(18%) progression, and 2(6%) died. Cytokines were measured in 22 patients, who were similar to the cohort as a whole except for more CCP positivity (p=0.02). CI patients with the small joint phenotype had higher levels of IL-6 than RA controls (p=0.04) (Figure 1) and IL-6 levels trended higher in the small joint vs. exclusively large joint phenotype (Figure 2). The B cell chemoattractant CXCL13, a factor produced by T peripheral helper cells in RA synovium1, trended higher in the serum of CI patients (Figure 3). Other cytokine levels did not differ significantly in patients with the small joint vs. exclusively large joint phenotype, or in CI-arthritis patients vs. cont...

Background:RA patients may cancel scheduled visits with their rheumatologist. In clinical practice, a validated patient-reported disease activity measure that tracks well with traditional clinical indices could address an important gap by providing real-time information on RA disease activity when a visit to the rheumatologist is not possible.Objectives:To assess concordance between the 5-item patient-reported Rheumatoid Arthritis Flare Questionnaire (RA-FQ) (1,2) and the Clinical Disease Activity Index (CDAI) in patients with early RA (ERA) treated in rheumatology clinics in 2 countries with different health systems.Methods:Data were analyzed from patients enrolled in the Canadian early ArThritis CoHort (CATCH) between Nov 2011 and March 2017 and in the Consortium of early ArThritis Cohorts- USA (CATCH-US) from Dec 2014 to Dec 2018. Both observational studies had a similar design; enrolled patients diagnosed with EIA (< 1 year of persistent symptoms) by a rheumatologist who completed similar regular protocolized clinical assessments, laboratory investigations and PROMs. The RA-FQ, designed to assess worsening of RA Inflammation, is a short composite PROM (total score 0-50) that sums 5 single items (NRS 0-10) querying pain, fatigue, stiffness, function and participation. The present analysis includes patients meeting ACR 1987 or 2010 ACR/EULAR criteria, with RA-FQ and CDAI at baseline and at least 1 other follow up (FU) over 12-months. We compared mean scores of the RA-FQ and CDAI over time and calculated intraclass correlation coefficients (ICC) to assess concordance between measures in the 2 cohorts.Results:The study included 818 Canadian and 75 American early RA patients. Age, male sex, and disease activity was higher in the Canadian cohort, while post-secondary education was higher in the US cohort (Table1). RA-FQ and CDAI scores tracked closely with one another over time in both cohorts (Canada ICC: 0.76; US ICC: 0.80)Conclusion:There was high concordance between the RA-FQ and CDAI measures over the 1st year of follow up in 2 early RA samples recruited in 2 countries. The RA-FQ may help patients and clinicians track patient disease activity between clinic visits.Table: Patient and Disease Characteristics at Study Entry Mean (SD) or% CATCH (N= 818) CATCH-US (n= 75) p Age, years55 (15)47 (16)<0.001Female,72%84%0.028Caucasian/White,80%76%0.401Education (High School or less)42%12%<0.001Symptom duration (months)5.5 (2.9)6.0 (3.3)0.188Seropositive (RF or ACPA),%74%77%0.690CDAI28.0 (14.0)14.4 (11.9)<0.001RA-FQ26.7 (13.3)16.0 (12.4)<0.001Figure 1Mean RA-FQ and CDAI scores over 12-months Follow Up in Canadian and US Early Rheumatoid Arthritis Cohorts.References:[1] Bykerk VP et al. RMD Open, 2016[2] Bartlett SJ et al. J Rheumatol. 2017Acknowledgement:CATCH: Amgen & pfizer-founding sponsors 2007+; abbvie 2011+; medexus 2013+; eli lilly 2016+, merck canada 2017+, hoffmann-laroche & janssen biotect 2011-2016, ucb & bms 2011-2018, sanofi-genzyme 2016-2017. catch-us: bms, ucb, genentech; cedar hill foundationDisclosure ...

Background:Non-articular pain (NAP) can co-exist with synovitis in RA. Its presence is associated with higher pain and worse function per legacy patient reported outcomes (PROs) both of concern to people with RA. It is not known if the presence of NAP significantly changes PROMIS 29 health domains.Objectives:To determine if co-existing NAP (both regional or widespread pain) is associated with important differences in PROMIS 29 domain scores for symptoms and impacts.Methods:Patients (pts) with early RA, were recruited from two practice settings in the Consortium of early arthritis cohorts, USA (CATCH-US) (New York and Baltimore) between Jan 2015-Dec 2019 (n=96). Data were from baseline (bl) visits; pts must have completed a body pain diagram (BPD) (CHOIR Bodymap®) and the PROMIS-29 V.1, and provided legacy PRO and clinical measures. Pts were grouped as i) no-NAP and ii) NAP based on presence of pain in non-articular regions (1-3 regions - regional, 4-5 -widespread). PROMIS 29 domain scores were compared between groups, as were related legacy PROs and clinical outcomes routinely used to assess disease activity. Data are descriptive; continuous variables were compared using t-tests.Results:Pts (n=96) had a mean age(sd) of 47.9 (14.9), 83% female, 67% white, 13% smokers, 21% obese, 82% seropositive, 51% mod/high CDAI, symptom duration 7.3 (5.4 months) and a comorbidity index (RDCI) of 0.7 (1.0). At study entry most had started RA treatments: 32% csDMARD with MTX, 22% non-MTX csDMARDs, 40% oral steroids, 13% biologics or JAKi’s; 28% were treatment naive. Patients reporting NAP were more often white, smokers, obese, but did not differ otherwise. MDSJC28 was higher, mostly effected small joints, and affected regions on BPD were excluded for NAP classification. All but one (anxiety) of PROMIS 29 domain scores differed significantly between groups; similar differences were seen in legacy PRO scores and in some clinical outcomes (Table). Most clinical measures did not differ between groups.Conclusion:In this cohort of early RA patients almost 1/3 with co-existent NAP unrelated to synovitis had significantly worse legacy PRO and PROMIS scores. These data provide rationale for using generic PROMIS measures as they identify symptoms and impacts, that may be unrelated to synovitis, providing information that could improve patient-oriented care in clinical practice. Clinicians should assess for and treat NAP as part of target-based care. Reasons for (injury, mechanical, disuse) and best treatment of NAP require further research.Table.PROMIS Scores differ between patients with and without NAP as do Legacy PROs in real world early RA patients.NAP Any Pattern (n=26)No Co-existing NAP (n=70)p-valueBaseline CharacteristicsAge50.2 (14.1)47.1 (15.1)0.356Female sex84%81%..Current Smoker19%5%..RF+ / ACPA+57% / 62%62% / 76 %..BMI27.2 (6.7)26.1 (6.4)0.236RDCI (0-9)0.68 (1.03)0.69 (0.97)0.963Symptom Duration, mos7.4 (1.3)7.4 (0.6)0.979Legacy PROs and Clinical MeasuresESR mm/hr22.5 (6.8)16.7 (2.3)0.425CRP (mg/dl)1.03 (0.260)1.02 (0.19)0.965Pain (0-10)4.5(2.4)3.0 (2.5)0.009Pt global (0-10)4.5 (2.6)2.6 (2.3)0.002Stiffness (0-10)5.1(2.5)3.07 (2.90)0.002MDHAQ (0-3)2.2 (1.7)0.9 (1.2)0.001RAPID 3 (0-10)2.8 (2.3)1.8 (1.8)0.036ESR mm/hr22.5 (6.8)16.7 (2.3)0.425CRP (mg/dl)1.03 (0.26)1.02 (0.19)0.965MDTJC 284.1 (5.4)2.9 (3.8)0.290MDSJC 286.9 (6.3)3.4 (3.9)0.013MD Global (0-10)4.1 (2.3)3.4 (2.0)0.183DAS28 ESR4.14 (2.25)3.14 (1.39)0.123CDAI19.6 (13.6)12.2 (9.5)0.015PROMIS ScoresFunction44.03 (8.79)49.47 (7.02)0.007Anxiety53.2 (10.5)50.4 (9.4)0.238Depression52.6 (9.2)47.1 (8.0)0.012Sleep Disturbance55.3 (8.4)50.3 (8.4)0.013Fatigue58.3 (7.9)49.3 (9.5)<.001Social Participation43.7 (9.9)50.7 (10.4)0.004Pain Interference60.2 (8.0)52.7 (8.9)0.007Data are mean(sd) unless notedDisclosure of Interests:Vivian Bykerk: None declared, Caroline Benson: None declared, Gregory Vitone: None declared, Aidan Tirpack: None declared, Susan J. Bartlett Consultant of: Pfizer, UCB, Lilly, Novartis, Merck, Janssen, Abbvie, Speakers bureau: Pfizer, UCB, Lilly, Novartis, Merck, Janssen, Abbvie, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb