Conventional Disease-modifying Antirheumatic Drugs Research Articles

One-Year Outcome of Critically Ill Patients With Systemic Rheumatic Disease: A Multicenter Cohort Study

Critically ill patients with systemic rheumatic disease (SRD) have benefited from better provision of rheumatic and critical care in recent years. Recent comprehensive data regarding in-hospital mortality rates and, most importantly, long-term outcomes are scarce. The aim of this study was to assess short and long-term outcome of patients with SRD who were admitted to the ICU. All records of patients with SRD who were admitted to ICU between 2006 and 2016 were reviewed. In-hospital and one-year mortality rates were assessed, and predictive factors of death were identified. A total of 525 patients with SRD were included. Causes of admission were most frequently shock (40.8%) and acute respiratory failure (31.8%). Main diagnoses were infection (39%) and SRD flare-up (35%). In-hospital and one-year mortality rates were 30.5%and 37.7%, respectively. Predictive factors that were associated with in-hospital and one-year mortalities were, respectively, age, prior corticosteroid therapy, simplified acute physiology score II≥50, need for invasive mechanical ventilation, or need for renal replacement therapy. Knaus scale C or D and prior conventional disease modifying antirheumatic drug therapy was associated independently with death one-year after ICU admission. Critically ill patients with SRD had a fair outcome after an ICU stay. Increased age, prior corticosteroid therapy, and severity of critical illness were associated significantly with short- and long-term mortality rates. The one-year mortality rate was also associated with prior health status and conventional disease modifying antirheumatic drug therapy.

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows.

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease affecting 0.5–1% of the population worldwide. Interstitial lung disease (ILD) is a serious pulmonary complication of RA and it is responsible for 10–20% of mortality, with a mean survival of 5–8 years. However, nowadays there are no therapeutic recommendations for the treatment of RA-ILD. Therapeutic options for RA-ILD are complicated by the possible pulmonary toxicity of many disease modifying anti-rheumatic drugs (DMARDs) and by their unclear efficacy on pulmonary disease. Therefore, joint and lung involvement should be evaluated independently of each other for treatment purposes. On the other hand, some similarities between RA-ILD and idiopathic pulmonary fibrosis and the results of the recent INBIULD trial suggest a possible future role for antifibrotic agents. From this perspective, we review the current literature describing the pulmonary effects of drugs (immunosuppressants, conventional, biological and target synthetic DMARDs and antifibrotic agents) in patients with RA and ILD. In addition, we suggest a framework for the management of RA-ILD patients and outline a research agenda to fill the gaps in knowledge about this challenging patient cohort.

Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that involves multiple joints bilaterally. It is characterized by an inflammation of the tendon (tenosynovitis) resulting in both cartilage destruction and bone erosion. While until the 1990s RA frequently resulted in disability, inability to work, and increased mortality, newer treatment options have made RA a manageable disease. Here, great progress has been made in the development of disease-modifying anti-rheumatic drugs (DMARDs) which target inflammation and thereby prevent further joint damage. The available DMARDs are subdivided into (1) conventional synthetic DMARDs (methotrexate, hydrochloroquine, and sulfadiazine), (2) targeted synthetic DMARDs (pan-JAK- and JAK1/2-inhibitors), and (3) biologic DMARDs (tumor necrosis factor (TNF)-α inhibitors, TNF-receptor (R) inhibitors, IL-6 inhibitors, IL-6R inhibitors, B cell depleting antibodies, and inhibitors of co-stimulatory molecules). While DMARDs have repeatedly demonstrated the potential to greatly improve disease symptoms and prevent disease progression in RA patients, they are associated with considerable side-effects and high financial costs. This review summarizes our current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.

P207 A quality improvement intervention to increase pneumococcal and influenza vaccination rates in immunosuppressed inflammatory arthritis patients

Abstract Background Pneumococcal and influenza vaccination rates have been suboptimal in studies of immunosuppressed patients. We aimed to assess barriers to and increase rates of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and influenza vaccination in this group. Methods In 2017, Rheumatology outpatients completed an anonymous questionnaire recording vaccination knowledge, status and barriers. Simultaneously, a low-cost multifaceted quality improvement (QI) intervention was performed. All outpatients on oral steroids, immunosuppressant conventional synthetic disease modifying antirheumatic drugs (csDMARDs) or biologics (bDMARDs) were included in the study. In 2018, post-intervention, the clinic was re-assessed. Demographics, diagnosis, medications, smart phone access and willingness to use this for vaccination reminders were assessed for independent vaccination predictors using binary logistic regression analysis. Results 425 patients were included (72.6% rheumatoid arthritis, 74% women, 45.6% ≥60 years old). From 2017-2018, vaccination rates increased for PPSV23 {41.0% to 47.2% (p = 0.29)} and influenza {61.8% to 62.1% (p = 0.95)}. The most common reason for non-vaccination was lack of awareness. Following the intervention, this decreased for influenza (36.7% to 34.2%) and PPSV23 (82.1% to 76.4%). General Practitioners performed most vaccinations, only 3.6% were delivered in hospital. Significant predictors of PPSV23 vaccination were older age {≥80 years had an OR 41.66 (95% CI 3.69-469.8, P = 0.003), compared to ≤ 39 years}, bDMARD use (OR 2.80, 95% CI 1.24-6.32, P = 0.013) and adequate influenza vaccination (OR 9.01, 95% CI 4.40-18.42, P < 0.001). Up to date PPSV23 vaccination (OR 8.93, 95% CI 4.39-18.17, P < 0.001) predicted influenza vaccination. Conclusion PPSV23 and influenza vaccination rates were suboptimal and increased marginally. Point-of-care vaccination may be more effective. Disclosures K. Murray: None. C. Low: None. F. Young: None. A. O'Rourke: None. I. Callanan: None. E. Feeney: None. D. Veale: None.

P252 Treatment pathways for patients with axSpA: a retrospective UK database analysis

Abstract Background This UK study aimed to identify a population with axial spondyloarthritis (axSpA) and to describe the presence of prior reported symptoms and treatment pathways associated with the condition. Methods The study was performed using a large routine primary care database from the UK, the Clinical Practice Research Datalink. Only patients whose record could be linked to Hospital Episode Statistics (HES) were included for analysis. Patients with an incident diagnosis of axSpA recorded from 2003-2017 were identified. The date of first axSpA diagnosis defined the index date and patients were observed until the end of database follow up. Recordings of axSpA-related symptoms (back pain, rheumatoid arthritis and fatigue) in the 12 months prior to the index date, before and after attendance at orthopaedic or rheumatology outpatient clinics, and after inpatient contact with either a primary or secondary diagnosis of axSpA were flagged. The proportion of patients prescribed tumour necrosis factor inhibitors (TNFis), corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) or conventional systemic disease-modifying anti-rheumatic drugs (csDMARDs) subsequent to the index date and estimated first three lines of therapy were described. Results A total of 2,756 incident axSpA cases were identified. In the 12 months prior to the index date, 1,289 (46.8%) of these patients had at least one recorded symptom related to axSpA: back pain (1,195 [43.4%]), rheumatoid arthritis (140 [5.1%]) and fatigue (6 [0.2%]). Prior to the index date, 1,025 (37.2%) patients had been seen in an orthopaedic outpatient clinic and 1,274 (46.2%) in a rheumatology clinic. Subsequent to the index date, the respective figures were 815 (29.6%) and 1,641 (59.5%). In addition, 133 (4.8%) patients had a post-index inpatient admission with a primary diagnosis of axSpA and 895 (32.5%) had an inpatient admission with a secondary diagnosis. TNFis were prescribed for 97 (3.5%) patients, corticosteroids for 727 (26.4%), NSAIDs for 1,885 (68.4%) and csDMARDs for 461 (16.7%) patients. The most common first-line therapy was NSAIDs (1,579 [57.3%]) (Table). Conclusion This study describes the symptoms of and treatment pathways for axSpA patients within the UK. Issues regarding missing data within routine data should be considered when interpreting the results. Disclosures C.L.I. Morgan: Other; Employee of: Pharmatelligence. A. White: Shareholder/stock ownership; Novartis. Other; Employee of: Novartis. M. Tomlinson: Consultancies; Novartis. A. Scott: Consultancies; Novartis. H. Tian: Other; Employee of: Novartis.

P283 Clinical predictors of switching biologic treatment in patients PsA: data from a single centre over 17 years

Abstract Background Management of PsA has included biologic agents (bDMARDs) since the early 2000s, in addition to conventional disease-modifying antirheumatic drugs (csDMARDs). Switching of bDMARD treatment is currently common clinical practice in treatment failure. Our aims were to determine the most prescribed first line bDMARDs, reasons for switching and any clinical factors at baseline that may predict switching in PsA. Methods Data was analysed retrospectively from a cohort of 400 PsA patients followed through from 2002-2019. Statistical analysis was carried out (logistic regression, analysis of variance and descriptive statistics) using SPSS version 22. Results The median age at baseline was 38.4 years (interquartile range [IQR] 29.8 - 53.3 years), 52.5% were female. bDMARDs were started in 220 of the 400 patients (55.0%). Initial therapy was a TNFi in 212 patients (96.3%). The median age of those started on bDMARDs was 33.7 years (IQR 27.5 - 48.2 years), 52.5% were female. The most frequently prescribed was adalimumab (59.5%), followed by etanercept (33.2 %) and infliximab (3.2%). 106 out of the 220 patients (48.2%) were on at least one concomitant csDMARD. 83 patients (37.8%) switched to a second bDMARD; 69 of these (83.1%) switched to a second TNFi. The commonest reasons for switching were primary or secondary inefficacy (61.0%) and adverse events (33.7%). The median duration on the first bDMARD was 11.6 months (IQR 3.8 - 30.1 months). Of the 83 patients who commenced a second bDMARD, 45 (54.2%) switched to a third bDMARD. The median duration on the second bDMARD was 10.0 months (IQR 3.0 - 33.0 months). The main reasons for the second switch were primary or secondary inefficacy (44.4%), adverse events (42.2%) and a combination of the two (11.1%). Patients who switched onto a second bDMARD were more frequently female (57.8%), had longer disease duration (14.01 versus 13.2 years), higher pain scores (84.2 versus 66.0) and higher tender/swollen joint counts compared to non-switchers at baseline. Patients using csDMARDs at baseline were more often responsive to initial bDMARD treatment than those on bDMARD alone (63.2% response versus 45.1%), but this was not statistically significant (p value >0.05). There was no significant change in drug survival of the first bDMARD if the patient was concurrently taking csDMARDS. A high ESR at baseline was associated with increased risk of switching from a second bDMARD to a third (odds ratio 1.20, p = 0.036). Conclusion We found that females, those with longer disease duration, higher subjective elements to disease activity at baseline were more likely to switch from initial bDMARD therapy. A high baseline ESR was associated with switching onto a third line bDMARD. Interestingly, the concurrent use of csDMARDs had no significant effect on the drug survival or efficacy of bDMARD therapy. Disclosures M. Naja None. L. R. Santos None. M. Greenwood None. M. Castelino None.

Favorable retention rates and safety of conventional anti-rheumatic drugs in older patients with rheumatoid arthritis.

Physicians are challenged by the recognition and treatment of older patients with rheumatoid arthritis (RA). The aim of this case-control study was to evaluate the retention and safety of conventional disease-modifying anti-rheumatic drugs in older patients with RA.In this observational case-control study, we assessed older patients with RA (≥65 years) who were diagnosed in 3 different rheumatology centers from Turkey. Patients were divided as to those aged ≥65 years (elderly rheumatoid arthritis [ERA]) and those aged <65 years (young rheumatoid arthritis [YRA]) at the time of conventional DMARD treatment initiation. The Mann-Whitney U test was used for the comparison of 2 non-normally distributed groups. The Chi-square (χ2) test was used for categorical variables. Survival analysis were performed using the Kaplan-Meier method.Four hundred eighteen patients with RA (296 females [71%]) were included from January 2010 to January 2018. The age of treatment onset of 190 (47%) patients was in the elderly period and they were included in the ERA group. In the analysis of drug retention rates, there was no significant difference between the ERA and YRA groups for each conventional DMARD (methotrexate 71.2% in ERA, 62.7% in YRA, P = .817; hydroxychloroquine 82.9% in ERA, 78.8% in YRA, P = .899; leflunomide 81.4% in ERA, 84.4% in YRA, P = .205; sulfasalazine 37.5% in ERA, 40.9% in YRA, P = .380). The adverse event data were also similar in both groups.The drug retention and adverse effect rates in older patients with RA using conventional DMARDS are similar to the rates in young patients with RA.

O09 Pooled safety analyses from Phase 3 studies of filgotinib in patients with RA

Abstract Background Filgotinib (FIL) is an oral, selective janus kinase 1 inhibitor under development for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. Safety and efficacy of FIL was investigated in the FINCH clinical program, which includes three Phase 3, summarized, summarized studies in patients with moderate to severely active RA. FINCH1: patients with inadequate response to MTX (NCT02889796); FINCH2: patients receiving conventional disease-modifying antirheumatic drugs (csDMARDs) with inadequate response to biological DMARDs (NCT02873936); FINCH3: MTX-naïve patients initiating MTX ± FIL, or receiving FIL monotherapy (NCT02886728). We present pooled safety data up to 24 weeks (W24). Methods The FINCH studies enrolled patients with RA (2010 ACR/EULAR criteria), ≥6 swollen joints and ≥6 tender joints at screening and Day 1. Safety analyses included patients receiving ≥1 dose of study drug. Patients in FINCH 1 and 2 who did not experience at least a 20% improvement in both swollen joint count and tender joint count by W14 discontinued study drug and switched to standard of care. W24 safety data from all studies were aggregated and ummarized. Key safety endpoints were treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of interest, deaths and treatment-emergent laboratory abnormalities. Results 3,452 patients were evaluated; 2,088 received FIL. At W24, the frequency of TEAEs and TEAEs of interest were similar for those who received FIL and those in the control groups (Table 1). Most TEAEs were infections. Laboratory abnormality rates were similar between FIL and control groups, and were mild to moderate (grades 1 and 2). Overall, the frequency of major adverse cardiac events, herpes zoster virus, deep vein thrombosis and pulmonary embolism was low, and similar across groups. Conclusion Pooled data from this large database highlights the favourable safety and tolerability profile of FIL in patients with RA both as monotherapy and in combination with MTX/csDMARD. Disclosures D. Walker: Other; Received support from Lilly, Pfizer, Novartis and Roche. K. Winthrop: Grants/research support; Received grants for clinical research from Bristol-Myers Squibb Company and Insmed Incorporated. Other; Received support from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly &amp; Co., MSD, Novartis, Pfizer, Roche-Chugai, Sanofi, and UCB. M.C. Genovese: Other; Gilead Sciences Inc., Galapagos NV, AbbVie Inc. Eli Lilly and Company, Pfizer. B.G. Combe: Honoraria; Honoraria from AbbVie, BMS, Gilead, Janssen, Eli Lilly and Co., MSD, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB. Y. Tanaka: Honoraria; Received from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly and Co., Pfizer, AbbVie, YL Biologics, BMS, Takeda, Misubishi-Tanabe, Novartis, Eisai, Janssen, Teijin. Grants/research support; Received grant support from Asahi-Kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, BMS, UCB, Daiichi-Sankyo, Eisai, and Ono. A. Kivitiz: Consultancies; Consultant for AbbVie, Celgene, Horizon, Janssen, Merck, Novartis, Pfizer, UCB, Genzyme,Sanofi, Regeneron, SUN Pharma Advanced Research, Boehringer Ingelheim and Flexion. Shareholder/stock ownership; Shareholder of Novartis. F. Matzkies: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. B. Bartok: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. L. Ye: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Gilead Sciences, Inc. Shareholder/stock ownership; Gilead Sciences, Inc. C. Tasset: Corporate appointments; Employee of Galapagos NV. J.S. Sundy: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. E. Keystone: Consultancies; AbbVie, Amgen, AstraZeneca Pharma, Biotest, BMS Canada, Celltrion, Crescendo, Bioscience, F.Hoffman-La Roche Inc., Genentech, Janssen, Eli Lilly and Co., Merck, Pfizer, PuraPharm, Sandoz,, Sanofi-Aventis, Sanofi- Genzyme Samsung Bioepsis, and UCB. Other; AbbVie, Amgen, AstraZeneca Pharma, Biotest, BMS Canada, Celltrion, Crescendo, Bioscience, F.Hoffman-La Roche Inc., Genentech, Janssen, Eli Lilly and Co., Merck, Pfizer, PuraPharm, Sandoz,, Sanofi-Aventis, Sanofi-Genzyme, Samsumg Bioepsis, and UCB. R. Westhovens: Corporate appointments; An investigator and advisor for Celltrion and Galapagos/Gilead. W. Rigby: Consultancies; Consultancy for Gilead. G.R. Burmester: Consultancies; Consultancy from AbbVie, Gilead, Eli Lilly, and Pfizer. Honoraria; Honoraria from AbbVie, Gilead, Eli Lilly, and Pfizer.

Safety update of etanercept treatment for moderate to severe plaque psoriasis

ABSTRACTIntroduction: Conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) for patients with psoriasis are often linked to inadequate outcomes and risk of multiple adverse effects. Biologic agents such as etanercept (ETN) have revolutionized the therapeutic management of psoriasis, allowing the treatment of most difficult cases, and fragile patients.Areas covered: The authors searched PubMed using the term ‘psoriasis,’ ‘etanercept,’ and ‘safety.’ Articles considered by the authors to be most relevant, such as randomized controlled studies, cohort studies, and review articles placing emphasis on studies of efficacy and safety were selected. Case reports and letters relating to safety were also included. The main sources of data referenced by these articles were also included in the review. Besides, to get the relevant studies, the reference lists were examined to identify the potentially available studies. The aim of this review is to describe the safety profile of ETN, used for psoriasis treatment, focusing on related clinical implications.Expert opinion: ETN has a favorable safety profile, and its use should be largely considered in psoriatic patients. Caution should be recommended in case of chronic heart failure, autoimmune disease, previous malignancies, familial history of demyelinating diseases, latent TBC infection, chronic HBV and HCV infection or HIV.

Clinical characteristics associated with drug-free sustained remission in patients with rheumatoid arthritis: Data from Korean Intensive Management of Early Rheumatoid Arthritis (KIMERA)

ObjectivesThere is limited information on treatment withdrawal in patients with rheumatoid arthritis (RA). This study investigated the clinical course after stopping disease-modifying anti-rheumatic drugs (DMARDs) in patients with well-controlled RA and the clinical features associated with disease flare. MethodsAmong patients in the Korean Intensive Management of Early Rheumatoid Arthritis (KIMERA) cohort, discontinuation of DMARDs was determined by a shared decision between patient and rheumatologist. Drug-free remission was defined as (1) non-use of DMARDs and corticosteroids, (2) Disease Activity Score in 28 joints (DAS28) <2.6, and (3) no evidence of synovitis. The maintenance rate of drug-free remission and the predictors for flare were evaluated using Cox proportional hazard models. ResultsOf 234 patients, 50 patients discontinued DMARDs. All but one using etanercept were treated with conventional synthetic DMARDs. The median follow-up duration was 30 months, and 31 patients (62%) experienced disease flare after stopping DMARDs. The maintenance rate of drug-free remission was 94.0%, 86.7%, and 46.1% at 12, 24, and 48 months, respectively. Disease flare was correlated with longer time to remission, failure of initial DMARDs, and longer duration of disease and higher disease activity at DMARD withdrawal (P = 0.001, 0.022, 0.010 and 0.037, respectively). In multivariate analyses, longer duration of disease (>24 months) and higher disease activity (DAS28 >2.26) at DMARD withdrawal was independently associated with disease flare. ConclusionDrug-free remission was feasible in selected patients with well-controlled RA. Patients with early RA and lower disease activity at DMARD withdrawal are more likely to maintain the drug-free remission.

Prime-boost vaccination strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients receiving conventional DMARDs, to some extent in abatacept but not in rituximab-treated patients

ObjectiveTo explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls.MethodsPatients receiving rituximab (n = 30), abatacept (n = 23), monotherapy with conventional disease-modifying antirheumatic drugs (cDMARDs, methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls (n = 28) were immunized with a dose PCV followed by PPV23 after ≥ 8 weeks. Specific antibodies to 12 serotypes included in both vaccines were determined using a multiplex microsphere immunoassay in blood samples before and 4–8 weeks after each vaccination. Positive antibody response was defined as ≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration and putative protective level as IgG ≥ 1.3 μg/mL. The number of serotypes with positive antibody response and IgG ≥ 1.3 μg/mL, respectively, after PCV and PCV + PPV23 were compared within each treatment group and to controls. Opsonophagocytic activity (OPA) assay was performed for serotypes 6B and 23F.ResultsCompared to single-dose PCV, prime-boost vaccination increased the number of serotypes with positive antibody response in patients with abatacept, cDMARDs, and controls (p = 0.02, p = 0.01, and p = 0.01), but not in patients on rituximab. After PCV + PPV23, the number of serotypes with positive antibody response was significantly lower in all treatment groups compared to controls but lowest in rituximab, followed by the abatacept and cDMARD group (p < 0.001). Compared to PCV alone, the number of serotypes with putative protective levels after PCV + PPV23 increased significantly only in patients in cDMARDs (p = 0.03) and controls (p = 0.001). Rituximab treatment was associated with large reduction (coefficient − 8.6, p < 0.001) and abatacept or cDMARD with moderate reductions (coefficients − 1.9 and − 1.8, p = 0.005, and p < 0.001) in the number of serotypes with positive antibody response to PCV + PPV23 (multivariate linear regression model). OPA was reduced in rituximab (Pn6B and Pn23F, p < 0.001), abatacept (Pn23F, p = 0.02), and cDMARD groups (Pn6B, p = 0.02) compared to controls.ConclusionsPrime-boost strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients with inflammatory rheumatic diseases receiving cDMARDs, to some extent in abatacept but not in patients on rituximab. Pneumococcal vaccination should be encouraged before the initiation of treatment with rituximab.Trial registrationClinicalTrials.gov, NCT03762824. Registered on 4 December 2018, retrospectively registered

Comparison of Early vs. Delayed Anakinra Treatment in Patients With Adult Onset Still's Disease and Effect on Clinical and Laboratory Outcomes

Background: Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment.Patients and Methods: One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed. Statistically significant differences (p < 0.05) were analyzed in the frequency of ANK effectiveness, primary or secondary inefficacy to ANK and rate of resolution of clinical and laboratory AOSD manifestations after 3, 6, and 12 months since ANK treatment according with different lines of treatment and different times between AOSD onset and start of ANK.Results: No significant differences were identified in the ANK effectiveness and frequency of primary or secondary inefficacy for patients starting ANK within 6 months (p = 0.19, p = 0.14, and p = 0.81, respectively) or 12 months (p = 0.37, p = 0.23, and p = 0.81, respectively) since AOSD onset compared with patients starting ANK thereafter; no significant differences were identified in ANK effectiveness and primary or secondary inefficacy according with different lines of ANK treatment (p = 0.06, p = 0.19, and p = 0.13, respectively). Patients starting ANK within 6 and 12 months since AOSD onset showed a significantly quicker decrease of erythrocyte sedimentation rate and C-reactive protein than observed among patients undergoing ANK treatment after 6 and 12 months. The number of swollen joints at the 3 month follow-up visit was significantly lower among patients undergoing ANK within 6 months since AOSD onset (p = 0.01), while no significance was identified at the 6 and 12 month assessments (p = 0.23 and p = 0.45, respectively). At the 3 and 6 month visits, the number of swollen joints was significantly higher among patients previously treated with conventional and biological disease modifying anti-rheumatic drugs (DMARDs) compared with those formerly treated only with conventional DMARDs (p < 0.017).Conclusions: Clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started in AOSD patients. However, a faster ANK effectiveness in controlling systemic inflammation and resolving articular manifestations may be observed in patients benefiting from IL-1 inhibition as soon as after disease onset.

Demodex Species Frequency and Risk Factors in Patients With Rheumatoid Arthritis.

Objectives This study aims to investigate the presence of Demodex species in rheumatoid arthritis (RA) patients, to identify the risk factors for developing Demodex infestation, and to determine the effect of immunosuppressant drugs on Demodex mite infestations.Patients and methods The study included 93 RA patients (16 males, 77 females; mean age 53.3±11.3 years; range, 27 to 83 years) and 76 healthy controls (19 males, 57 females; mean age 50.3±13.9 years; range, 19 to 86 years). Specimens were collected from face skin by using standardized sur- face skin biopsy. Demodex infestation was considered for ≥5 living parasites/cm2 of skin while Demodex mite presence was defined as any Demodex larvae, adults, or eggs found in the specimen.Results The frequencies of Demodex mite presence were 44% for the RA patients and 15.7% for the healthy controls (p<0.001). The rates of Demodex infestation were similar between the two groups (18.3% versus 7.9%, p=0.054). There were no statistically significant differences between the groups regarding skin type, skin care, epilation, body washing, use of a moisturizer, personal towel use, the number of residents at home, or whether there were pets at home or in proximity. Itching in eyes was higher in RA patients, but the frequency of other skin symptoms was not differ- ent from healthy controls. Logistic regression analysis indicated that the diagnosis of RA was an independent risk factor for Demodex mite presence in this study population. Disease activity and duration, use of corticosteroids, conventional disease-modifying anti-rheumatic drugs (DMARDs) and biological DMARDs were not effective factors on Demodex mite presence in RA patients.Conclusion Although Demodex mite presence was 3.5-fold higher in RA patients, the rate of Demodex infestation was similar to that of healthy controls.

Regulatory T Cell Suppressive Activity Predicts Disease Relapse During Disease-Modifying Anti-rheumatic Drug Dose Reduction in Rheumatoid Arthritis: A Prospective Cohort Study.

When the dose of conventional disease-modifying anti-rheumatic drugs (cDMARDs) is tapered in rheumatoid arthritis (RA) patients who achieve sustained remission, biomarkers for predicting disease relapse may be needed. A prospective, unblinded cohort study was conducted in nine RA patients with remission. Peripheral blood samples were collected at baseline and at 6, 12, and 24 weeks after cDMARD dose reduction (dose of combination regimens reduced to 50%) to determine the number of regulatory Foxp3+T cells (Tregs) and other T cell subpopulations as well as Treg suppressive activity. Additionally, plasma levels of 14 cytokines at each time-point were measured via flow cytometry. Univariate and multivariate analyses were performed to identify the factor(s) associated with RA relapse during the observational period. In univariate analysis, Treg suppression and DAS28 and VAS scores were associated with RA relapse after cDMARD dose tapering. However, in multivariate analysis, only Treg suppressive activity (<42%) was found to be an independent factor associated with RA relapse after cDMARD dose reduction to 50%. Of all patients who had ≥42% Treg suppressive activity during cDMAD reduction, three-fourth patients remained in the remission stage for 24 weeks. Treg suppressive activity (<42%) in RA patients with remission could be a potential biomarker for predicting RA relapse after cDMARD dose reduction, especially over a short-term period (24 weeks).

Evaluation of hepatitis B virus in clinical trials of baricitinib in rheumatoid arthritis

BackgroundReactivation of hepatitis B virus (HBV) replication is a well-recognised complication in patients receiving disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA). Limited data exist on HBV reactivation among patients...

Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Multicenter Retrospective Study.

Background: Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA). Methods: All RA-ILD patients treated with ABA for at least six months were retrospectively evaluated. Serology, previous and concurrent therapies, chest high-resolution computer tomography (HRCT), forced vital capacity (FVC), and lung diffusion of carbon monoxide (CO, DLCO) were collected. Results: Forty-four patients were included; HRCT, FVC, and DLCO were analyzed at baseline, at one year, and at the end of follow-up. A remission or a low disease activity of RA was reached in 41/44 patients. Overall, FVC and DLCO remained stable or increased in 86.1% and 91.7% of patients, respectively, while HRCT was stable or improved in 81.4% of them. Previous and concurrent treatments, in particular, methotrexate, serology, age, sex, joint and lung disease duration were not associated with the outcome at univariate analysis. Conclusion: The management of RA-ILD patients remains a critical unmet medical need. Waiting for prospective controlled studies, ABA has shown a good safety profile in our cohort of Italian RA-ILD patients.

P597 Pooled safety analyses from Phase 3 studies of filgotinib in patients with rheumatoid arthritis

Abstract Background Filgotinib (FIL) is an oral, selective Janus Kinase 1 inhibitor under development for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. Safety and efficacy of FIL was investigated in the FINCH clinical program, which includes three Phase 3, randomised, multicentre studies in patients with moderate to severely active RA. FINCH1: patients with inadequate response to MTX (NCT02889796); FINCH2: patients receiving conventional disease-modifying antirheumatic drugs (csDMARDs) with inadequate response to biological DMARDs (NCT02873936); FINCH3: MTX-naïve patients initiating MTX ± FIL, or receiving FIL monotherapy (NCT02886728). We present pooled safety data up to 24 weeks (W24). Methods The FINCH studies enrolled patients with RA (2010 ACR/EULAR criteria), ≥6 swollen joints and ≥6 tender joints at screening and Day 1. Safety analyses included patients receiving ≥1 dose of study drug. Patients in FINCH 1 and 2 who did not experience at least a 20% improvement in both swollen joint count and tender joint count by W14 discontinued study drug and switched to a standard of care. W24 safety data from all studies were aggregated and summarised. Key safety endpoints were treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of interest, deaths and treatment-emergent laboratory abnormalities. Results 3452 patients were evaluated; 2088 received FIL. At W24, the frequency of TEAEs and TEAEs of interest were similar for those who received FIL and those in the control groups (Table 1). Most TEAEs were infections. Laboratory abnormality rates were similar between FIL and control groups, and were mild to moderate (grades 1 and 2). Overall, the frequency of major adverse cardiac events, herpes zoster virus, deep vein thrombosis and pulmonary embolism was low, and similar across groups. Conclusion Pooled data from this large database highlights the favourable safety and tolerability profile of FIL in patients with RA both as monotherapy and in combination with MTX/csDMARD.

Association of Seropositivity and Mortality in Rheumatoid Arthritis and the Impact of Treatment With Disease‐Modifying Antirheumatic Drugs: Results From a Real‐World Study

ObjectiveSeropositivity for anti–citrullinated protein antibody (ACPA)/rheumatoid factor (RF) in rheumatoid arthritis (RA) is associated with increased overall mortality; however, the association between antibody titers and mortality is not well established. Investigating relationships between antibody titers and mortality may clarify their role in RA pathogenesis. This study was undertaken to evaluate the association of antibody titers with mortality and its modification by disease‐modifying antirheumatic drugs (DMARDs).MethodsEligible patients with established RA were identified through administrative claims data linked to laboratory results (2005–2016). Patients were categorized by positivity status for ACPA, RF, or both. Patients were further divided into groups by autoantibody titers. DMARD‐exposed patients were categorized into biologic DMARD (bDMARD) and conventional DMARD (cDMARD) subcohorts. Crude mortality rates/1,000 patient‐years and Kaplan‐Meier curves were compared between antibody categories. Adjusted Cox proportional hazards regression and sensitivity (propensity‐matched patients) analyses were conducted.ResultsOverall, 53,849 and 79,926 patients had evaluable ACPA and RF status, respectively. For both autoantibodies, mortality rates were significantly higher in seropositive versus seronegative patients (risk increase of 48.0% and 44.0% in ACPA‐ and RF‐positive patients, respectively; P < 0.001 each). Mortality rates were greatest in patients with higher versus lower autoantibody titers (ACPA hazard ratio [HR] 1.60 [95% confidence interval (95% CI]) 1.45–1.76]; RF HR 1.78 [95% CI 1.66–1.91]). In cDMARD‐exposed patients, HRs were higher in seropositive versus seronegative cohorts; in bDMARD‐exposed patients, there was no difference in mortality by serostatus.ConclusionElevated ACPA/RF titers were independently associated with increased mortality among patients with RA and persisted in patients treated with cDMARDs but not with bDMARDs.

Timing matters: real-world effectiveness of early combination of biologic and conventional synthetic disease-modifying antirheumatic drugs for treating newly diagnosed polyarticular course juvenile idiopathic arthritis

ObjectivesTo compare real-world effectiveness of two adaptive treatment strategies of disease-modifying antirheumatic drugs (DMARDs) in treating children with newly diagnosed polyarticular course juvenile idiopathic arthritis (pcJIA): early aggressive use of...

Uveitis in spondyloarthritis.

Uveitis is the most frequent extra-articular manifestation of axial spondyloarthritis (SpA), occurring in up to one-third of the patients. In the majority of patients, uveitis is acute, anterior and unilateral and presents with photosensitivity, sudden onset of pain and blurred vision. Topical steroids are an effective treatment; however, recurrent or refractory cases may need conventional disease-modifying antirheumatic drugs or biological treatment with monoclonal tumor necrosis factor (TNF) inhibitors, thus also influencing treatment strategy of the underlying SpA.Though the exact pathogenesis of SpA and uveitis remains unknown, both seem to result from the interaction of a specific, mostly shared genetical background (among other HLA-B27 positivity), external influences such as microbiome, bacterial infection or mechanical stress and activation of the immune system resulting in inflammation. Up to 40% of patients presenting with acute anterior uveitis (AAU) have an undiagnosed SpA. Therefore, an effective referral strategy for AAU patients is needed to shorten the diagnostic delay of SpA and enable an early effective treatment. Further, the risk for ophthalmological manifestations increases with the disease duration in SpA; and patients presenting with ocular symptoms should be referred to an ophthalmologist. Thus, a close collaboration between patient, rheumatologist and ophthalmologist is needed to optimally manage ocular inflammation in SpA.