Disease Activity Outcomes Research Articles

Impact of clinical domains other than arthritis on composite outcomes in psoriatic arthritis: comparison of treatment effects in the SEAM-PsA trial

ObjectiveWe used the Study of Etanercept And Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) data set to examine the impact of presence of enthesitis, dactylitis,...

Treatments for AIDS/HIV-related Kaposi sarcoma: A systematic review of the literature.

Treatment guidelines are not well established in AIDS-related Kaposi sarcoma (KS). We aim to review the evidence on efficacy of treatments for AIDS-related Kaposi sarcoma. We searched the Cochrane Library, PubMed, and Embase Database from date of database inception till July 2020. Randomized controlled trials reporting intervention consisting of any type of treatment compared to control/placebo to a different treatment modality or different combination of treatment/treatment doses with a diagnosis of AIDS-related KS are selected. Primary outcomes were response rates defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Secondary outcomes were cosmesis and adverse outcomes such as pain and erythema. Thirteen out of 536 articles met our eligibility criteria. Three studies reported the efficacy of chemotherapy, two studies looked at different doses of radiotherapy regimes, and three studies compared different antiretroviral therapy (ART) and chemotherapy regimens. Other studies reported topical therapies such as alitretinoin gel, IM862, and bHCG injection which showed varied efficacies. Lack of standardization classification of disease activity and clinical outcomes and treatment modalities precluded meaningful comparison of studies. The evidence of efficacy of any particular intervention is overall varied and there was insufficient evidence to recommend any particular intervention. We have provided an overview of treatments for KS but larger studies need to be carried out to verify the efficacy of treatment options reported in the literature.

Ojeok-san ameliorates visceral and somatic nociception in a mouse model of colitis induced colorectal cancer.

Cancer patients can develop visceral, somatic, and neuropathic pain, largely due to the malignancy itself and its treatments. Often cancer patients and survivors turn to the use of complementary and alternative medicine (CAM) to alleviate pain and fatigue. Thus, it is necessary to investigate how CAM therapies work as novel analgesics to treat cancer pain. Ojeok-san (OJS) is an herbal formula consisting of seventeen herbs. This herbal formula has been shown to possess anti-inflammatory, immunoregulatory, and analgesic properties. In this study, we examined the potential beneficial effects and mechanism of action of OJS in a preclinical model of colitis-associated colorectal cancer. Male and female C57BL/6J mice were exposed to the carcinogen, azoxymethane (AOM, 10 mg/kg) and a chemical inflammatory driver, dextran sulfate sodium (DSS1-2%), to promote tumorigenesis in the colorectum. OJS was given orally (500, 1000, and 2000 mg/kg) to determine its influence on disease activity, tumor burden, nociception, sedation, Erk signaling, and behavioral and metabolic outcomes. In addition, in vitro studies were performed to assess CT-26 cell viability, dorsal root ganglia (DRG) activation, and bone-marrow-derived macrophage (BMDM) inflammatory response to lipopolysaccharide stimulation after OJS treatment. We found that administration of 2000 mg/kg of OJS was able to mitigate mechanical somatic and visceral nociception via Erk signaling without affecting symptom score and polyp number. Moreover, we discovered that OJS has sedative properties and elicits prolonged total sleeping time in AOM/DSS mice. Our in vitro experiments showed that OJS has the capacity to reduce TNFα gene expression in LPS-stimulated BMDM, but no changes were observed in DRG spike number and CT-26 cell proliferation. Taken together, these data suggest that OJS ameliorates nociception in mice and warrants further examination as a potential CAM therapy to promote analgesia.

Prediction Aided Tapering In rheumatoid arthritis patients treated with biOlogicals (PATIO): protocol for a randomized controlled trial

BackgroundBiological disease-modifying anti-rheumatic drugs (bDMARDs) are effective in the treatment of rheumatoid arthritis (RA) but are expensive and increase the risk of infection. Therefore, in patients with a stable low level of disease activity or remission, tapering bDMARDs should be considered. Although tapering does not seem to affect long-term disease control, (short-lived) flares are frequent during the tapering process. We have previously developed and externally validated a dynamic flare prediction model for use as a decision aid during stepwise tapering of bDMARDs to reduce the risk of a flare during this process.MethodsIn this investigator-initiated, multicenter, open-label, randomized (1:1) controlled trial, we will assess the effect of incorporating flare risk predictions into a bDMARD tapering strategy. One hundred sixty RA patients treated with a bDMARD with stable low disease activity will be recruited. In the control group, the bDMARD will be tapered according to “disease activity guided dose optimization” (DGDO). In the intervention group, the bDMARD will be tapered according to a strategy that combines DGDO with the dynamic flare prediction model, where the next bDMARD tapering step is not taken in case of a high risk of flare. Patients will be randomized 1:1 to the control or intervention group. The primary outcome is the number of flares per patient (DAS28-CRP increase > 1.2, or DAS28-CRP increase > 0.6 with a current DAS28-CRP ≥ 2.9) during the 18-month follow-up period. Secondary outcomes include the number of patients with a major flare (flare duration ≥ 12 weeks), bDMARD dose reduction, adverse events, disease activity (DAS28-CRP) and patient-reported outcomes such as quality of life and functional disability. Health Care Utilization and Work Productivity will also be assessed.DiscussionThis will be the first clinical trial to evaluate the benefit of applying a dynamic flare prediction model as a decision aid during bDMARD tapering. Reducing the risk of flaring during tapering may enhance the safety and (cost)effectiveness of bDMARD treatment. Furthermore, this study pioneers the field of implementing predictive algorithms in clinical practice.Trial registrationDutch Trial Register number NL9798, registered 18 October 2021, https://www.trialregister.nl/trial/9798. The study has received ethical review board approval (number NL74537.041.20).

Risk factors for adverse pregnancy outcomes in women with rheumatoid arthritis and follow-up of their offspring.

To explore the risk factors for adverse pregnancy outcomes (APOs) in women with rheumatoid arthritis (RA) and the influence on their offspring health. Pregnant women with RA (n = 67) who were hospitalized in the Department of Obstetrics, Peking University People's Hospital between January 2007 and September 2021 were included in this study. Participants were evaluated at least once in each trimester and postpartum. Fetal outcomes and RA disease activity were extracted from medical records, and the offspring of enrolled patients were followed up. Associations between RA disease activity, medication use, and pregnancy outcomes were analyzed. The incidence of APOs in our cohort was 43.3%. Postpartum hemorrhage (20.9%) was the commonest complication, followed by premature delivery (11.9%). Previous miscarriages [odds ratio (OR): 1.869, 95% confidence interval (CI): 1.053-3.318, P = 0.033] and antinuclear antibody (ANA) positivity (OR:3.168, 95% CI: 1.068-9.768, P = 0.045) were risk factors for APOs. Compared to patients with APOs, the remission rate of disease activity during pregnancy was higher in patients without APOs (P = 0.027). There were no significant differences between patients with and without APOs with respect to daily and cumulative doses of prednisone (P > 0.05). The average age of the offspring was 4.9years (range 0.3-14years). Long-term follow-up showed no significant differences in offspring health between the two groups (P > 0.05). Previous miscarriages and ANA positivity are independent risk factors for APOs in RA patients, while adverse pregnancy outcomes and low-dose prednisone have no effect on offspring health. Key points • Previous miscarriages and ANA positivity are risk factors for APOs in RA patients. • Adverse pregnancy outcomes and low-dose prednisone during pregnancy have no effect on offspring health.

Association of Peripheral Blood and Cutaneous Eosinophils With Bullous Pemphigoid Disease Severity and Treatment Outcomes

Background and aimsA dermal inflammatory infiltrate rich in eosinophils is a prominent histological feature of bullous pemphigoid (BP) and peripheral blood eosinophilia has been documented in 50–60% of BP patients. Nevertheless, the impact of circulating and dermal infiltrate eosinophil levels on BP remains poorly understood. The main objective of this work was to investigate the association of peripheral blood and dermal infiltrate eosinophil levels with clinical and immunological characteristics of the disease. Material and methodsRetrospective cohort study including all patients diagnosed with BP between 2011 and 2020. ResultsThe study cohort included 233 patients with BP. The mean baseline peripheral blood eosinophil count was 956.3±408.6×106/L and the mean number of tissue eosinophils at the dermal hot spot area was 30.5±19.0. Patients with disseminated presentation (i.e. BSA>50%) had significantly higher peripheral blood eosinophil counts (P=0.028). Mucosal involvement was significantly associated with lower dermal eosinophil count (P=0.001). Requiring inpatient care and relapsing were significantly associated with high peripheral blood eosinophil count (P=0.025; P=0.020, respectively). Among the 68 patients who experienced a relapse, 31 had peripheral blood eosinophilia (i.e. >500×106/L) at relapse (44.2%). Peripheral blood eosinophil counts at baseline and at relapse were significantly correlated (r=0.82, P<0.001). ConclusionsPeripheral blood and cutaneous eosinophils levels may be useful biomarkers for disease activity and treatment outcomes in BP. Monitoring peripheral blood eosinophil counts may allow early detection of relapse.

POS0683 EFFICACY AND SAFETY OF UPADACITINIB IN TNFi-IR PATIENTS WITH RHEUMATOID ARTHRITIS FROM THREE PHASE 3 CLINICAL TRIALS

BackgroundFor patients with RA who are refractory to biologic DMARDs (bDMARDs), such as tumor necrosis factor inhibitors (TNFis), optimal disease control is less likely to be achieved with subsequent therapy.1 In line with recommendations from EULAR and ACR, switching to a treatment with a different mechanism of action is appropriate for these patients.ObjectivesTo describe the efficacy and safety of upadacitinib (UPA) 15 mg once daily in patients with RA and an inadequate response or intolerance to TNFis (TNFi-IR).MethodsA post hoc subgroup analysis was conducted in TNFi-IR patients who were treated with UPA 15 mg once daily in three Phase 3 clinical trials: SELECT-BEYOND,2 -CHOICE,3 and -COMPARE.4 For COMPARE, only patients treated with adalimumab and switched to UPA as rescue therapy were included. ≥20/50/70% improvement in ACR criteria, DAS28(CRP), CDAI, and SDAI, as well as change from baseline in HAQ-DI and other patient-reported outcomes (PROs) were reported through 24 weeks. Non-responder imputation was used for all missing categorical outcomes; as observed (COMPARE) or multiple imputation (CHOICE, BEYOND) were used for missing continuous outcomes. Pooled safety results were presented as exposure-adjusted event rates (EAERs) with a cut-off of June 30, 2021.Results568 TNFi-IR patients were included: 146 from BEYOND, 263 from CHOICE, and 159 from COMPARE. Mean duration since RA diagnosis was longer for BEYOND and CHOICE versus COMPARE; cardiovascular (CV) risk factors were common among this refractory population (Table 1). ACR20/50/70 and disease activity outcomes observed in the TNFi-IR population were generally consistent with the overall BEYOND2 and CHOICE3 bDMARD-IR populations, and consistent across the three studies in the TNFi-IR subgroups (Figure 1). Improvements in PROs including HAQ-DI, fatigue, pain, and morning stiffness over 24 weeks were observed (data not shown). Pooled safety results reporting 1574.8 patient-years (PY) of exposure in the TNFi-IR subgroup showed similar results to the overall BEYOND2 and CHOICE3 bDMARD-IR study populations, with EAERs of 3.1 events/100 PY for herpes zoster and 0.8 events/100 PY for adjudicated major adverse CV events, adjudicated venous thromboembolism (VTE), and malignancy excluding non-melanoma skin cancer. The EAER of any AE leading to death was 1.4 events/100 PY.Table 1.Baseline characteristics of TNFi-IR patients treated with UPA 15 mgn (%), unless specifiedSELECT-BEYOND (n=146)SELECT-CHOICE (n=263)SELECT-COMPARE (ADA → UPA) (n=159)Female122 (83.6)219 (83.3)133 (83.6)Mean (SD) age, years56.6 (11.0)55.5 (11.1)53.9 (10.6)Mean (SD) duration of RA diagnosis, years13.2 (9.5)12.5 (9.4)8.2 (8.5)Concomitant csDMARDs MTX alone100 (70.4)195 (74.1)159 (100.0) MTX and other csDMARDs20 (14.1)25 (9.5)0 csDMARDs other than MTX22 (15.5)38 (14.4)0Concomitant oral steroids73 (50.0)140 (53.2)98 (61.6)1 prior bDMARD68 (46.6)172 (65.4)142 (89.3)2 prior bDMARDs40 (27.4)62 (23.6)17 (10.7)a≥3 prior bDMARDs38 (26.0)29 (11.0)0Failed ≥1 prior TNFi due to lack of efficacyb131 (89.7)223 (84.8)159 (100.0)History of VTE / CV event3 (2.1) / 28 (19.2)6 (2.3) / 20 (7.6)4 (2.5) / 14 (8.8)CV risk factors Hypertension72 (49.3)109 (41.4)68 (42.8) Diabetes mellitus22 (15.1)34 (12.9)17 (10.7) Smoking (current former past)68 (46.6)109 (41.5)55 (34.6) Elevated LDL-C (≥3.36 mmol/L)38 (26.0)52 (20.0)48 (30.2) Low HDL-C (≤1.55 mmol/L)80 (54.8)171 (65.0)88 (55.3)aThese patients received one bDMARD before entry into SELECT-COMPARE.bRemaining patients were intolerant to ≥1 prior TNFi.ConclusionIn this post hoc subgroup analysis, TNFi-IR patients treated with UPA 15 mg achieved clinically meaningful efficacy responses over 24 weeks, with safety consistent with the overall bDMARD-IR patient population in the Phase 3 program.

Long-term drug effectiveness and survival for reference rituximab in rheumatoid arthritis patients in an ordinary outpatient clinic

To explore the long-term drug effectiveness and survival of reference rituximab (ref-RTX)-treated rheumatoid arthritis (RA) patients in an ordinary outpatient clinic. Second, we explored baseline predictors of drug effectiveness and survival, and third, we clarified reasons for stopping treatment. RA patients treated with ref-RTX between 2006 and 2020 in Norway were examined and monitored using recommended measures for disease activity and patient-reported outcomes (PROs). Drug effectiveness was assessed with random intercept linear mixed models; drug survival was assessed with Kaplan–Meier survival analysis. Reasons for discontinuation were ascertained. Baseline predictors of drug effectiveness and survival were estimated. Among 246 RA patients, at baseline, 17.1% were biologic disease-modifying anti-rheumatic drugs (bDMARDs) naïve, and 51.6% were currently using conventional synthetic DMARDs (csDMARDs). During the five-year follow-up, all disease activity and PRO measures improved significantly (p < 0.01), with more substantial changes noted in the second year. Drug survival was 83% after one year and declined to 34% after five years. The two most frequently reported reasons for discontinuation were the doctor’s decision (36.2%) and lack or loss of effectiveness (19.2%). No significant difference was found between naïve and previous users of bDMARDs or between concomitant and nonconcomitant users of csDMARDs when analysing drug effectiveness and survival. Our real-life data show that ref-RTX-treated RA patients had satisfactory treatment responses; drug survival declined linearly over time. There was no significant difference between naïve and previous users of bDMARDs or between concomitant and nonconcomitant users of csDMARDs, both for drug effectiveness and survival.

Impact of previous disease-modifying treatment on safety and efficacy in patients with MS treated with AHSCT

BackgroundAutologous haematopoietic stem cell transplantation (AHSCT) is a highly effective treatment for multiple sclerosis (MS). The impact of previous long-lasting disease-modifying treatments (DMT) for safety and efficacy of AHSCT is...

P044 Giant cell arteritis in an immunocompromised patient with rheumatoid arthritis

Abstract Background/Aims Giant cell arteritis (GCA) is a common medium-large vessel vasculitis with an approximate incidence of 10 cases per 100,000 people over 50 years old. First line management of GCA is with high dose glucocorticoids followed by steroid sparing agents, namely methotrexate with tocilizumab for resistant cases. Here we describe a patient established on methotrexate for rheumatoid arthritis, receiving rituximab with intravenous methylprednisolone (IVMP) who went on to develop GCA. Methods A 65-year-old Caucasian female with seropositive rheumatoid arthritis (RA) established on 20mg weekly subcutaneous methotrexate and low dose 5mg prednisolone was escalated to her tenth cycle of rituximab with 100mg IVMP for an arthritic flare. The day after her second infusion, two weeks apart, the patient presented with headaches. These were severe temporal pains with scalp tenderness for the past four weeks. She denied visual changes, jaw claudication or polymyalgia rheumatica features. Examination identified bilateral thickened and tender temporal arteries. Ultrasound confirmed bilateral frontal temporal artery halo signs, with intimal thickening of 0.9mm and 0.4mm of the left and right respectively. Blood tests showed a rise in C-reactive protein to 46mg/L from 13mg/L. In view of these findings, procedural risks and recent immunosuppression biopsy was not sought. The patient was commenced on 40mg prednisolone before weaning by 5 mg 2-3 weekly. Her headache improved, without relapse and her CRP normalised within 2 weeks. Given tocilizumab had previously been ineffective in the patient’s RA management, she declined transition to this biologic and her methotrexate was increased to 25mg. Results Development of GCA in a patient with pre-established immunotherapy is rare. This report represents only the second case noted in the literature of the vasculitis occurring in a patient whilst on rituximab. Excluding tocilizumab (anti-IL6), a meta-analysis of other biological agents including infliximab, adalimumab, etanercept (anti-TNF) and abatacept (anti-CTLA4) have not been proven to have clinical significance over placebo in GCA. However, evidence of rituximab and its role in GCA is limited with no clinical trials. Contrary to this case of GCA, rituximab (anti-CD20) therapy has a well-recognised role in ANCA associated vasculitis and there are growing calls for trials in large vessel vasculitides. Recent case series of rituximab in Takayasu’s arteritis have presented contrasting outcomes of persistent disease activity versus clinical and laboratory remission. Robust clinical trials are therefore required to evaluate the long-term impact of rituximab on large vessel vasculitis. Conclusion Although rare, clinicians should be vigilant for the development of GCA despite established immunosuppression. Disclosure N. Chauhan: None. A. Kinder: None.

P266 Secukinumab provides clinical improvements in patients with active oligoarticular psoriatic arthritis: results from a pooled analysis of five phase 3 studies

Abstract Background/Aims Evidence for the efficacy of biologics in patients with oligoarticular psoriatic arthritis (PsA) is limited. We evaluated the efficacy of the interleukin 17 inhibitor secukinumab in patients with oligoarticular PsA pooled from 5 phase 3 studies. Methods This post hoc analysis included patients with oligoarticular PsA from the FUTURE 2-5 and MAXIMISE trials (NCT01649375, NCT01989468, NCT02294227, NCT02404350, and NCT02721966). Oligoarticular PsA was defined as the presence of 1-4 tender joints and 1-4 swollen joints at baseline as measured by the tender joint count of 78 joints (TJC78) and the swollen joint count of 76 joints (SJC76), respectively. Patients were pooled by treatment received at week 12 and week 52 in the following groups: week 12 (secukinumab 300 mg, secukinumab 150 mg with or without loading dose [LD], or placebo) and week 52 (any secukinumab 300 mg or any secukinumab 150 mg). Efficacy was assessed by the proportion of patients achieving 50% improvement in Disease Activity in Psoriatic Arthritis (DAPSA50), DAPSA75, DAPSA-based low disease activity (LDA; DAPSA ≤14) and remission (REM; DAPSA ≤4), resolution of TJC78, resolution of SJC76, and a ≥ 0.35-point improvement in the Health Assessment Questionnaire-Disability Index score. Descriptive statistics are provided for each endpoint. Logistic regression analysis was used to identify potential predictors of DAPSA response at weeks 12 and 52; multivariate logistic regression analyses were performed thereafter. Results 84 patients were included: 48 with active PsA from the FUTURE 2-5 trials and 36 with active PsA and axial manifestations from the MAXIMISE trial. Demographics and baseline disease characteristics were comparable across groups. At week 12, notable improvements were observed for the secukinumab 300 and 150 mg versus placebo groups across all the assessed outcome measures and were sustained or increased through week 52. More than 78% of patients who received secukinumab 300 mg or secukinumab 150 mg achieved LDA or REM at week 12. More than 90% of patients who received any secukinumab 300 mg or secukinumab 150 mg achieved LDA or REM at week 52. At week 52, a higher proportion of patients who received any secukinumab 300 mg versus any secukinumab 150 mg achieved higher hurdle endpoints of DAPSA75 (58.1% versus 43.6%, respectively) and DAPSA REM (61.3% versus 37.5%, respectively). At week 12, younger age was a predictor for the achievement of DAPSA LDA or REM and the achievement of DAPSA50, while lower baseline SJC was a predictor of the achievement of DAPSA REM (P &amp;lt; 0.05). No predictors were identified at week 52. Conclusion Secukinumab provides greater improvements versus placebo across a number of disease activity and physical function outcome measures in patients with oligoarticular PsA at week 12, with sustained responses through week 52. Disclosure L.C. Coates: Honoraria; AbbVie, Amgen, Celgene, Galapagos, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Celgene, Eli Lilly, Novartis, Pfizer. A. Ogdie: Consultancies; Amgen, AbbVie, BMS, Celgene, Novartis, Lilly, Janssen, Gilead, Pfizer, UCB. Grants/research support; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Rheumatology Research Foundation, National Psoriasis Foundation, Amgen, Pfizer, Novartis. D.D. Gladman: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Galapagos, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Pfizer, UCB. E. Pournara: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. X. Meng: Other; Employee of Novartis. B. Parikh: Other; Employee of Novartis. P.J. Mease: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, UCB. Member of speakers’ bureau; AbbVie, Amgen, Janssen, Eli Lilly, Novartis, Pfizer, UCB. Grants/research support; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, UCB.

New indicator for discordance between patient-reported and traditional disease activity outcomes in patients with early rheumatoid arthritis.

To unravel disease impact in early RA by separately quantifying patient-reported (PRF), clinical (CF) and laboratory (LF) factors. We propose a new indicator, the discordance score (DS), for early identification and prediction of patient's unmet needs and of future achievement of sustained remission (SR) and RA-related quality of life (QoL). Factor-scores obtained by factor analysis in the CareRA trial, allowed to compute DS, reflecting the difference between PRF and the mean of CF and LF. Improvement from baseline to week 104 (%) and area-under-the-curve (AUC) across time points per factor-score were calculated and compared between patients achieving/not achieving sustained (week 16-104) remission (DAS28CRP < 2.6) with ANOVA. Logistic and linear regressions were used to predict SR based on previous factor and discordance scores, and QoL at year 1 and 2 based on DS at week 16. PRF, CF and LF scores improved rapidly within 8 weeks. PRF improved 57%, CF 90% and LF 27%, in those achieving SR, compared with 32% (PRF: P = 0.13), 77% (CF: P < 0.001) and 9% (LF: P = 0.36) in patients not achieving SR. Patients achieving SR had an AUC of 15.7, 3.4 and 4.8 for PRF, CF and LF, respectively, compared with 33.2, 10.1 and 7.2 in participants not achieving SR (P < 0.001 for all). Early discordance was associated with later factor scores, QoL and self-efficacy. All factor scores improved rapidly, especially in patients achieving sustained remission. Patient-reported burden improved less. Discordance scores could help predicting the need for additional non-pharmacological interventions to achieve sustained remission and decrease disease impact.

Isolation in patients with inflammatory rheumatic diseases during COVID-19 pandemic compared to healthy individuals: a questionnaire survey.

As a result of the pandemic, many patients with an inflammatory rheumatic disease (IRD) have isolated themselves. The lack of disease management together with fear of infection could lead to changes in physical- and mental health. The aim of this study was to evaluate the social- and health behaviour in patients with an IRD compared with the behaviour of healthy individuals during the COVID-19 pandemic. The study was a questionnaire survey answered by patients with an IRD and healthy individuals (HI). The questionnaire contained seven sections with questions regarding COVID-19 and quality of life including SF-36, EQ-5D-5L, and visual analogue scale (VAS) pain, fatigue and global health. Of 1663 invited participants, 661 patients with IRD and 266 HI were included in the analyses. Patients with an IRD felt more isolated during the COVID-19 pandemic compared with HI (IRD: 9.5% (61/644), HI: 3.1% (8/259), p-value = 0.001). More HI (5.4%) had been infected with COVID-19 than patients with an IRD (1.7%). Among patients with an IRD those with worse self-reported disease activity outcomes (VAS pain, fatigue and global health, all p-value < 0.001), worse social functioning and emotional well-being were more isolated than individuals with low disease activity. Patients with an IRD feel more isolated during the COVID-19 pandemic compared to HI. Isolation seems to be most pronounced in patients with worse disease related patient-reported outcomes and lower quality of life.

Role of Telemedicine in Inflammatory Bowel Disease: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BackgroundTelemedicine plays an important role in the management of inflammatory bowel disease (IBD), particularly during a pandemic such as COVID-19. However, the effectiveness and efficiency of telemedicine in managing IBD are unclear.ObjectiveThis systematic review and meta-analysis aimed to compare the impact of telemedicine with that of standard care on the management of IBD.MethodsWe systematically searched the PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases on April 22, 2020. Randomized controlled trials comparing telemedicine with standard care in patients with IBD were included, while conference abstracts, letters, reviews, laboratory studies, and case reports were excluded. The IBD-specific quality of life (QoL), disease activity, and remission rate in patients with IBD were assessed as primary outcomes, and the number of in-person clinic visits per patient, patient satisfaction, psychological outcome, and medication adherence were assessed as secondary outcomes. Review Manage 5.3 and Stata 15.1 were used for data analysis.ResultsA total of 17 randomized controlled trials (2571 participants) were included in this meta-analysis. The telemedicine group had higher IBD-specific QoL than the standard care group (standard mean difference 0.18, 95% CI 0.01 to 0.34; P.03). The number of clinic visits per patient in the telemedicine group was significantly lower than that in the standard care group (standard mean difference −0.71, 95% CI −1.07 to −0.36; P<.001). Subgroup analysis showed that adolescents in the telemedicine group had significantly higher IBD-specific QoL than those in the standard care group (standard mean difference 0.42, 95% CI 0.15 to 0.69; I2=0; P.002), but there was no significant difference between adults in the 2 groups. There were no significant differences in disease activity, remission rate, patient satisfaction, depression, self-efficacy, generic QoL, and medication adherence outcomes between the telemedicine and standard care groups.ConclusionsTelemedicine intervention showed a promising role in improving IBD-specific QoL among adolescents and decreased the number of clinic visits among patients with IBD. Further research is warranted to identify the group of patients with IBD who would most benefit from telemedicine.

Clinical Outcome Assessments in Pediatric Patients With Ulcerative Colitis and Crohn's Disease Receiving Biologics: A Retrospective Cohort Study.

To assess disease activity, steroid-free remission, and other clinical outcome assessments among pediatric patients with ulcerative colitis (UC) and Crohn's disease (CD) in the ImproveCareNow (ICN) registry. Patients aged 2-17 years diagnosed with UC or CD between June 1, 2013 and December 31, 2019 were enrolled if they initiated a biologic after enrollment in the ICN registry and completed at least 12 months follow-up after first maintenance dose. Baseline (at biologic initiation) demographics were summarized using descriptive statistics. Pediatric UC Activity Index (PUCAI), partial Mayo score, and Physician Global Assessment (PGA) were assessed for UC; and the Short Pediatric Crohn's Disease Activity Index (sPCDAI) and PGA were assessed for CD at first maintenance dose, 1- and 3-year time points. Kappa coefficients were used to assess the level of agreement between the outcome measures. A total of 1887 patients (UC = 350; CD = 1537) were included. Baseline demographics were similar across groups. For UC patients, mean PUCAI scores decreased and the proportion of patients in steroid-free remission, quiescent state based on PGA, and remission based on partial Mayo score increased from first maintenance dose to 1 and 3 years. For CD patients, mean sPCDAI score of CD patients decreased and the proportion of patients in steroid-free remission by sPCDAI and in quiescent state based on PGA increased from first maintenance dose to 1 and 3 years. Kappa coefficients showed only modest correlation between disease activity assessments. Disease activity scores improved over time, with more pediatric patients with UC and CD achieving steroid-free remission at 1 and 3 years after first biologic maintenance dose.

The clinical and molecular cardiometabolic fingerprint of an exploratory psoriatic arthritis cohort is associated with the disease activity and differentially modulated by methotrexate and apremilast.

Objectives(1) To evaluate clinical and molecular cardiovascular disease (CVD) signs and their relationship with psoriatic arthritis (PsA) features and (2) to identify a clinical patient profile susceptible to benefit from methotrexate (MTX) and/or apremilast regarding CVD risk.MethodsThis cross‐sectional study included 100 patients with PsA and 100 age‐matched healthy donors. In addition, an exploratory cohort of 45 biologically naïve patients treated for 6 months with apremilast, MTX or combined therapy according to routine clinical practice was recruited. Extensive clinical and metabolic profiles were obtained. Ninety‐nine surrogate CVD‐related molecules were analysed in plasma and peripheral blood mononuclear cells (PBMCs). Hard cluster analysis was performed to identify the clinical and molecular phenotypes. Mechanistic studies were performed on adipocytes.ResultsCardiometabolic comorbidities were associated with disease activity and long‐term inflammatory status. Thirty‐five CVD‐related proteins were altered in the plasma and PBMCs of PsA patients and were associated with the key clinical features of the disease. Plasma levels of some of the CVD‐related molecules might distinguish insulin‐resistant patients (MMP‐3, CD163, FABP‐4), high disease activity (GAL‐3 and FABP‐4) and poor therapy outcomes (CD‐163, LTBR and CNTN‐1). Hard cluster analysis identified two phenotypes of patients according to the rates of cardiometabolic comorbidities with distinctive clinical and molecular responses to each treatment.Conclusions(1) Novel CVD‐related proteins associated with clinical features could be emerging therapeutic targets in the context of PsA and (2) the pleiotropic action of apremilast could make it an excellent choice for the management of PsA patients with high CVD risk, targeting metabolic alterations and CVD‐related molecules.

The Clinical Significance of Eosinophils in Ulcerative Colitis: A Systematic Review.

Ulcerative colitis [UC] is characterised by an unpredictable disease course and variable response to therapy. Recent studies suggest a role for eosinophils in both pathogenesis and predicting treatment response. The goal of this study was to determine the association between eosinophils and clinical outcomes in UC. A systematic review of the literature from database inception to May 2021 was performed to identify all studies evaluating the relationship between eosinophils and/or eosinophil-derived proteins [EDPs] and clinical outcomes, such as disease activity, clinical relapse, severity of disease, and response to treatment. A total of 55 studies were identified. Of these, 34 studies evaluated the relationship between eosinophils in colonic tissue and outcomes and 15 in blood. Eighteen studies assessed the relationship between EDPs and outcomes. In 25 of 34 studies, a positive correlation between eosinophils and/or EDPs and disease activity was reported, three studies found a negative correlation, and nine studies found no correlation. Positive correlations between eosinophils and clinical relapse were shown in four of nine studies, and with disease outcome severity in five of seven studies. Four of 15 studies showed that subjects with higher eosinophil levels had a poor response to treatment. These findings suggest that higher eosinophil levels may be associated with increased disease activity and poorer clinical outcomes and response to therapy. Future studies are needed to determine whether a distinct eosinophil-rich UC phenotype exists and whether eosinophil-targeted therapy can alter the disease course.

Effect of high-intensity exercise on cardiorespiratory fitness, cardiovascular disease risk and disease activity in patients with inflammatory joint disease: protocol for the ExeHeart randomised controlled trial

IntroductionInflammatory joint disease (IJD) is associated with increased risk of cardiovascular disease (CVD) fostered by systemic inflammation and a high prevalence of CVD risk factors. Cardiorespiratory fitness (CRF) is an...

Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis

Lipid mediators are crucial for the pathogenesis of rheumatoid arthritis (RA); however, global analyses have not been undertaken to systematically define the lipidome underlying the dynamics of disease evolution, activation, and resolution. Here, we performed untargeted lipidomics analysis of synovial fluid and serum from RA patients at different disease activities and clinical phases (preclinical phase to active phase to sustained remission). We found that the lipidome profile in RA joint fluid was severely perturbed and that this correlated with the extent of inflammation and severity of synovitis on ultrasonography. The serum lipidome profile of active RA, albeit less prominent than the synovial lipidome, was also distinguishable from that of RA in the sustained remission phase and from that of noninflammatory osteoarthritis. Of note, the serum lipidome profile at the preclinical phase of RA closely mimicked that of active RA. Specifically, alterations in a set of lysophosphatidylcholine, phosphatidylcholine, ether-linked phosphatidylethanolamine, and sphingomyelin subclasses correlated with RA activity, reflecting treatment responses to anti-rheumatic drugs when monitored serially. Collectively, these results suggest that analysis of lipidome profiles is useful for identifying biomarker candidates that predict the evolution of preclinical to definitive RA and could facilitate the assessment of disease activity and treatment outcomes.

Acromegaly and pregnancy: a systematic review and meta-analysis.

To evaluate the association between acromegaly and pregnancy in terms of disease activity, maternal and fetal outcomes. This systematic review was conducted according to the Joanna Briggs Institute methodology for systematic reviews of etiology and risk. We focused on observational studies that included pregnant women with acromegaly. The outcomes were acromegaly activity, preterm birth, gestational diabetes, hypertension, eclampsia/preeclampsia, miscarriage, perinatal mortality, low birthweight, small for gestational age, and congenital malformations. Embase, Medline, LILACS, and CENTRAL were our source databases. To perform proportional meta-analyses, we used Stata Statistical Software 17. Nineteen studies were included encompassing a total of 273 pregnancies in 211 women with acromegaly. The overall frequency of control of acromegaly during pregnancy was 62%, and of tumor growth was 9%. No fetal or maternal deaths were reported. The overall frequency of worsening of previous diabetes or development of gestational diabetes was 9%, and of previous hypertension or preeclampsia/eclampsia was 6%. The overall frequency of premature labor was 9% [from 17 studies of 263 pregnancies; 95% confidence interval (CI), 5-13%]; of spontaneous miscarriage was 4% (from 19 studies of 273 pregnancies; 95% CI, 2-11%); of small for gestational age was 5% (from 15 studies of 216 newborns; 95% CI, 3-9%); and of congenital malformations was 1% (from 18 studies of 240 newborns; 95% CI, 0-7%). Pregnancy in women with acromegaly is frequently associated with disease control and is safe in relation to fetal and maternal outcomes, as in women without acromegaly.