Background:Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder. In recent years biological disease modifying antirheumatic drugs (bDMARDs) are becoming increasingly important for its treatment.Objectives:To evaluate disease outcomes, treatment strategies and their long-term safety in a cohort of AOSD patients treated with bDMARDs.Methods:A single-center retrospective study of patients diagnosed with AOSD until 2019 was conducted. Patients were included if they: a) were 16 years old or older, b) met the Yamaguchi criteria and c) had received a bDMARDDemographics, clinical and laboratory parameters were collected at the time of diagnosis.Data regarding treatment lines included: the previous and concomitant conventional disease modifying antirheumatic drugs (cDMARDs), the type of initial bDMARD, switches, survival and corticosteroids discontinuation. Adverse events related to treatment and disease outcomes including death and amyloidosis were also recorded.Results:Sixteen patients with AOSD (Table 1) refractory to cDMARDs were administered biologics. The median duration of follow-up was 14 years (range 1-24). Consistent with recent literature1, two distinct disease patterns were recognized: the systemic form (SF) and the chronic articular form (CAF). In the SF the leading clinical symptoms were fever, pericarditis and pleuritis. In CAF the leading clinical symptom was persistent RA-like arthritis.Table 1.Some clinical and laboratory features of patients with FMF or MEFV mutations accompanied by demyelination diseaseCasesAge/SexDiseasesMEFV mutationsThe onset age/diagnostic age for FMFThe onset age for DD/MS/Presenting manifestations/MRI findingsTreatment for FMF /DD/MSCase 1(F1)17/FFMF+DDM694V homozygous3/515OB (-)Fusiform plaques in the cingulate gyrus; plaques in T4-6ColchicineIL-1 RAGlatiramer acetateCase 2(F1)46/FFMF+MSM694V homozygous8/928Optic nerve involvementOB(+)Plaques (+)ColchicineGlatiramer acetateCase 3(F1)17/FFMF+MSM694V heterozygous3/515Loss of the right eye, vertigoOB(+)PlaquesColchicinePulse steroidBeta-interferonTeriflunomideCase 4(F2)36/FMS+MEFV mutationM694V/R202Q-27Headache, blurred vision, optic nerve atrophyOB(+)Plaques (+)Glatiramer acetateCase 5(F2)16/FMS?+FMF+Cutaneous vasculitisM694V/R202Q16/1611Headache, blurred visionNo LP (denied by pt)Plaques-F: Female, F1: Family 1, F2: Family 2; DD: Demyelination disease;MS: Multiple sclerosis;MRI: Magnetic resonance imaging; OB:Oligoclonal band; LP: Lumbar punctionTable 1.Summary of patient characteristics at the time of diagnosisCharacteristicsResultsAge at the time of diagnosis median, (range) years32.5 (18-64)Sex (N)11 female, 5 maleFever14 (87.5%)Rash8 (50%)Lymphadenopathy2 (12.5%)Arthritis15 (93.75%)Pleuritis7 (43.7%)Pericarditis9 (56.25%)Hepatosplenomegaly2 (12.5%)Elevated liver enzymes2 (12.5%)Hyperferritinaemia4 (25%)Patients with the SF were treated with anakinra (n=4), tocilizumab (TCZ; n=3), canakinumab (n=1) and anti-TNFa (1 adalimumab, 1 etanercept) (n=2). Patients with the CAF received anti-TNFa (3 infliximab, 1 etanercept) (n=4) and TCZ (n=2). The median time from biologic initiation to corticosteroids discontinuation was 6.5 months, (range 2-32), (Table 2). 9 patients (56.25%) remained on treatment with the initial bDMARD, 4 patients (25%) received treatment with two and 3 patients (18.75%) with ≥ 3 bDMARDs. All patients with the CAF were on bDMARD at the end of follow-up, while 4/10 patients (40%) with the SF discontinued it. During follow-up only one serious adverse event was attributed to bDMARD (allergic reaction to infliximab infusion). There were no cases of amyloidosis or deathsConclusion:Dichotomous phenotype in AOSD can determine treatment strategy for initial biologic treatment. Inhibition of IL-1 and IL-6 was the preferred therapeutic option for systemic form while inhibition of TNF and IL-6 was the preferred option for the chronic articular form. All of the above bDMARDs have favorable long-term safety profile in patients with AOSD.References:[1]François Vercruysse et al. Adult-onset Still’s disease biological treatment strategy may depend on the phenotypic dichotomy Arthritis Research & Therapy. 2019Disclosure of Interests:Nikolaos Kougkas: None declared, Nestor Avgustidis: None declared, Sofia Pitsigavdaki: None declared, Katerina Pateromichelaki: None declared, ARGYRO REPA: None declared, Ainour Molla Ismail Sali: None declared, Anastasios Eskitzis: None declared, George Bertsias Grant/research support from: GSK, Consultant of: Novartis
BackgroundData regarding effectiveness and persistence to therapy with anti-IL17 agent secukinumab (SEC) in spondyloarthritis (SpA) patients of real world clinical practice are very limited.ObjectivesTo assess characteristics of SpA patients starting therapy with SEC versus tumor necrosis factor inhibitors (TNFis) in routine clinical care and compare clinical responses and treatment retention at 2 years.MethodsAll patients starting a bDMARD in the Rheumatology Department of the University Hospital of Heraklion, Crete, are included in a prospective observational study after their written informed consent. Data concerning disease activity at pre-specified time-points, drugs, comorbidities and any adverse events are recorded. For the present study we analyzed all consecutive patients with axial (AxSpA) or peripheral SpA (pSpA) starting or switching bDMARD therapy, either a TNFi or SEC from 1/2015 till 12/2018. We excluded patients with IBD-related SpA, patients starting ustekinumab (or apremilast) and patients switching from a bio-originator to a biosimilar TNFi. We compared disease activity scores improvement at 6 months using linear regression analysis and treatment retention using Kaplan-Meier survival curves with log-rank test and Cox regression. Inverse propensity score weighting (IPW) was used to adjust for the potential confounding of gender, age, disease duration, previous bDMARDs and csDMARDs number, diagnosis (AxSpA vs pSpA), presence of peripheral arthritis and co-therapy with csDMARDs.ResultsA total of 239 patients with SpA started/switched bDMARD (SEC:69, TNFis:170). SEC was the ≥3rd bDMARD in 63% of patients compared to 17% of TNFis (p<0.001). Patients’ characteristics at baseline were comparable except for disease duration (median (IQR): 5 (1.5-11) years in SEC vs. 0.9 (0.2-4.6) in TNFis, p<0.001). AxSpA was the diagnosis in 78% patients starting SEC and 79% starting TNFis while peripheral arthritis was slightly more common with SEC (81% vs 76% in TNFis). Monotherapy tended to be more common with SEC compared to TNFis (52% vs 42%, p=0.16). Baseline disease activity regarding both axial and peripheral arthritis was comparable in the two groups.Unadjusted 2-year treatment retention was similar in the two groups, both overall (SEC: 63%, TNFi: 56%, p=0.18) and due to failure or adverse events. However, when we selected only patients on 1st or 2nd bDMARD (SEC:26, TNFis:131), 2-year survival of SEC was higher than that of TNFis (95% vs. 57%, p=0.027). Similarly, SEC tended to have higher survival than TNFis in patients with pSpA (p=0.11). After IPW, SEC administration was an independent predictor for higher bDMARD retention overall [HR (95%CI)=0.48(0.33-0.69), p<0.001] and specifically due to discontinuation for failure [HR=0.58 (0.38-0.88), p=0.011] and for adverse events [HR=0.21 (0.08-0.62), p=0.004].Mean BASDAI and ASDAS improvements at 6 months were similar in patients with AxSpA receiving SEC or TNFis [Mean(SD) δBASDAI: 1.6 (2.5) vs 1.4(2.5) respectively (p=0.78) and δASDAS: 0.7 (1.4) vs 1.0 (1.5), p=0...
Background:Difficult-to-treat rheumatoid arthritis (D2T RA) was recently defined by a EULAR study group (1) and, as a disease category it is largely complicated and under-researched. Patient comorbidities may play a significant role in the response to therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) and in the disease classification as D2T RA.Objectives:To evaluate the impact of comorbidities [studied as total Comorbidities Count (CC) and rheumatic disease comorbidity index (RDCI)] on 6-month response to therapy with the first bDMARD in real-world clinical practice and on eventual disease designation as D2T RA.Methods:Prospective study of all RA patients who start any bDMARD in a tertiary centre University Hospital after their consent. All patient comorbidities [among a list of approximately 100 pre-specified major comorbidities] are registered by treating physicians. Response to therapy was defined as achievement of low disease activity or remission (LDA/Rem) according to simplified disease activity index (SDAI) and health assessment questionnaire (HAQ) improvement of ≥ 0.25.D2T RA patient group was defined according to the EULAR definition of D2T RA and was compared to: a/ all other patients and b/ to a sub-group of patients designated as “well-controlled RA” (follow-up ≥2 years and ≥2 visits in the last year in LDA/Rem).Logistic regression models were used to adjust for the potential confounding of age, sex, disease duration, seropositivity, number of previous synthetic DMARDs, type of 1st bDMARD initiated (TNF inhibitor vs. non-TNF inhibitor), co-administered methotrexate and corticosteroids (yes/no), baseline SDAI and HAQ and year of therapy start.Results:Analysis included 501 RA patients who received a total of 1098 bDMARD treatments. At 1st bDMARD treatment start, patients (women: 81%) had a median (IQR) age: 60 (51-68) years, disease duration: 5.4 (3-11) years, SDAI: 36 (28-46), HAQ: 1.0 (0.5-1.5), CC: 3 (2-6) και RDCI: 2 (0-3).In adjusted analyses, total comorbidity count (CC) ≤1 (vs ≥ 2) was predicting LDA/Rem at 6 months of therapy [OR (95%CI) = 4.1 (1.5-11), p=0.005], while RDCI=0 (vs. ≥ 1) was predicting HAQ improvement ≥ 0.25 [OR (95% CI) = 2.6 (1.2-6.7), p=0.046].During 2614 patient-years of follow-up, the disease in 98 patients could be classified as “D2T RA”, while 127 patients had “well-controlled RA”. Baseline independent predictors for D2T RA compared to all other patients were RDCI ≥ 1 (vs. 0) [OR = 3.3 (1.7-9.4), p = 0.024], female sex [OR =3.1 (1.01-9.5)] and age [OR = 0.97 (0.94-0.99)]. Multivariable analyses for predictors of “D2T” compared to “well-controlled” RA yielded similar results.Conclusion:In RA patients starting the first bDMARD treatment, a higher number of comorbidities at baseline is an independent predictor of lower 6-month response to therapy and final disease classification as “difficult-to-treat” RA.References:[1]Nagy G, Roodenrijs NM, Welsing PM, Kedves M, Hamar A, van der Goes MC, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31–5.Acknowledgements:Pancretan Health Association and Special Account for Research Grants (ELKE) – University of Crete.Disclosure of Interests:None declared.
BackgroundSystemic sclerosis (SSc) is characterized by systemic autoimmunity, vasculopathy and fibrosis. Nailfold Videocapillaroscopy (NVC) is a safe method to detect and to analyze morphological microvascular abnormalities in SSc patients. There is circumstantial evidence to suggest an association between NVC abnormalities and disease severity, particularly vascular manifestations.1 ObjectivesTo evaluate the association of NVC patterns with demographic, clinical, laboratory features and disease progression in the SSc cohort of University Hospital of Heraklion.MethodsRetrospective study (2011-2018) of SSc patients who underwent NVC. NVC findings were classified into three distinct patterns namely early, active and late according to Cutolo et al2 . NVC patterns were correlated with the clinical characteristics of the patients. We also correlated baseline NVC patterns with the progression of the disease at 3 years.Results62 patients [(88.8% women, mean age of diagnosis 49.8 years, range 18-82)] were included. Compared to early/active pattern, patients with late pattern were more likely to have diffuse SSc (dSSc) (p=0.006), interstitial Lung Disease (ILD) (80.0% vs 38.1% p=0.002) and esophageal involvement (80.0% vs 47.6% p=0.0034). There was a trend for increased frequency of Pulmonary arterial Hypertension (PAH), digital ulcers (DU) and calcinosis in patients with late pattern (p=0.079, p=1.103 and p=0.079 respectively). Patients with active NVC pattern were more likely to have arthritis (early/active/late: 36.4%/75.9%/55.0%, p=0.054). A total 42 patients had NVC data at the time of SSc diagnosis. At 3 years there were no significant differences regarding disease progression, although patients with late NVC pattern had more hospitalizations due to infections (33.3% vs 9.1%, p=0.191), higher death rate (16.7% vs. 8.3%, p=0.543), need to use cyclophosphamide (33.3% vs 17.4%, p=0.391) and/or bosentan (40.0% vs 22.7%, p=0.426).ConclusionIn this single-center SSc cohort, NVC pattern was found to correlate with organ involvement especially ILD, esophageal involvement and dSSc. Serious infections and treatment intensification were also more frequent among patients with late NVC pattern. NVC may be a useful prognostic marker for SSc patients.References[1] Paxton Det al, Semin arthritis Rheum. 2018Dec;48(3):482-494[2] Cutolo M, et al. Assessing microvascular changes in systemic sclerosis diagnosis and management, Nat Rev Rheumatol. 2010AcknowledgementThis study was funded by Hellenic Society of Rheumatology & Professionals Union of Rheumatologists of GreeceDisclosure of interestsNone declared
Background:Long-term observational studies of patients under biologic disease-modifying anti-rheumatic drug (bDMARD) therapies in routine clinical practice can provide us with important data regarding patients with comorbidities, who are usually excluded from randomized controlled studies.Objectives:To study the impact of comorbidities in the outcome (response and persistence to therapy) of patients with spondyloarthritis (SpA) receiving bDMARDs in real-world clinical practice.Methods:Prospective study of all patients who start a bDMARD in a tertiary centre University Hospital after their consent. All patient comorbidities [among a list of approximately 100 pre-specified major comorbidities] are registered by treating physicians at baseline and during follow-up.Comorbidities were studied as total Comorbidities Count (CC) and rheumatic disease comorbidity index (RDCI). Statistical analyses were performed using logistic and Cox regression models, adjusting for the potential confounding of age, sex, disease duration, diagnosis (axial vs. peripheral SpA), number of previous conventional synthetic and biologic DMARDs, year of therapy start, and co-administered methotrexate and corticosteroids (yes/no). Analyses of response to therapy also included baseline BASDAI or ASDAS indices as confounding variables.Results:A total of 603 biologic treatments (1st: 298, 2nd: 157, ≥3rd: 148) were analyzed. Half (51%) of the patients were female, 413 patients had axial SpA (AxSpA) and 190 peripheral SpA (perSpA). At baseline, median (IQR) age: 48 (38-57) years, disease duration: 11 (4-19) years, CC: 2 (1-4) and RDCI: 1 (0-2). Both comorbidity indices were significantly higher in perSpA compared to AxSpA (p<0.001).At 6 months of therapy, 31% of patients with AxSpA achieved BASDAI50 and 39% had ASDAS-ESR < 2.1. Higher CC was an independent predictor of insufficient response according to BASDAI50 [OR (95%) = 0.70 (0.52-0.94), p=0.019] and higher RDCI was predicting failure to achieve ASDAS-ESR < 2.1 [OR (95%) = 0.59 (0.37-0.94), p=0.027]. Other independent predictors of non-response were age, longer disease duration and (for ASDAS-ESR<2.1) higher baseline disease activity.During 1405 patient-years of follow-up, 349 (58%) treatments were discontinued. The adjusted hazard ratio for bDMARD discontinuation within the first 2 years of treatment due to insufficient response was doubled in patients with CC ≥2 versus those with CC ≤1 [HR = 2.27 (1.14-4.53), p=0.020] or with RDCI ≥1 (vs. RDCI = 0) [HR = 2.23 (1.22-4.07), p=0.009]. Comorbidities’ indices were not significant predictors of treatment discontinuations due to adverse events.Conclusion:The presence of comorbidities in patients with SpA is an independent predictor for insufficient 6-month response to bDMARDs and resultant treatment discontinuation due to failure.Acknowledgements:This research is co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning» in the context of the project “Reinforcement of Postdoctoral Researchers - 2nd Cycle” (MIS-5033021), implemented by the State Scholarships Foundation (ΙΚΥ).Disclosure of Interests:None declared
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