Higher Baseline Disease Activity Research Articles

Latent Class Analysis Identifies Distinct Phenotypes of Systemic Lupus Erythematosus Predictive of Flares after mRNA COVID-19 Vaccination: Results from the Coronavirus National Vaccine Registry for ImmuNe Diseases SINGapore (CONVIN-SING).

Six hundred and thirty-three SLE patients from eight public healthcare institutions were divided into test and validation cohorts based on healthcare clusters. Latent class analysis was performed based on age, ethnicity, gender, vaccine type, past COVID-19 infection, interruption of immunomodulatory/immunosuppressive treatment for vaccination, disease activity and background immunomodulatory/immunosuppressive treatment as input variables. Data from both cohorts were then combined for mixed effect Cox regression to determine which phenotypic cluster had a higher risk for time to first SLE flare, adjusted for the number of vaccine doses. Two clusters were identified in the test (C1 vs. C2), validation (C1' vs. C2') and combined (C1″ vs. C2″) cohorts, with corresponding clusters sharing similar characteristics. Of 633 SLE patients, 88.6% were female and there was multi-ethnic representation with 74.9% Chinese, 14.2% Malay and 4.6% Indian. The second cluster (C2, C2' and C2″) was smaller compared to the first. SLE patients in the second cluster (C2 and C2') were more likely to be male, non-Chinese and younger, with higher baseline disease activity. The second cluster (C2″) had more incident flares (hazard ratio = 1.4, 95% confidence interval 1.1-1.9, p = 0.014) after vaccination. A higher proportion of patients in C2″ had immunomodulatory/immunosuppressive treatment interruption for vaccination as compared to patients in C1″ (6.6% vs. 0.2%) (p < 0.001). We identified two distinct phenotypic clusters of SLE with different patterns of flares following mRNA COVID-19 vaccination. Caution has to be exercised in monitoring for post-vaccination flares in patients with risk factors for flares such as non-Chinese ethnicity, young age, male gender and suboptimal disease control at the time of vaccination.

Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study

Interleukin-5 (IL-5) inhibitors represent novel therapies for eosinophilic granulomatosis with polyangiitis (EGPA). This study assessed the effectiveness and safety of the IL-5 receptor inhibitor benralizumab in a European cohort of patients with EGPA. This retrospective cohort study included patients with EGPA from 28 European referral centres of the European EGPA Study Group across six countries (Italy, France, UK, Russia, Spain, and Switzerland) who received benralizumab as any line of treatment between Jan 1, 2019, and Sep 30, 2022. We assessed the rates of complete response, defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] of 0) and a prednisone dose of up to 4 mg/day, in contrast to partial response, defined as a BVAS of 0 and a prednisone dose greater than 4 mg/day. Active disease manifestations, pulmonary function, variation in glucocorticoid dose, and safety outcomes were also assessed over a 12-month follow-up. 121 patients with relapsing-refractory EGPA treated with benralizumab at the dose approved for eosinophilic asthma were included (64 [53%] women and 57 [47%] men; median age at the time of beginning benralizumab treatment 54·1 years [IQR 44·2-62·2]). Complete response was reported in 15 (12·4%, 95% CI 7·1-19·6) of 121 patients at month 3, 25 (28·7%, 19·5-39·4) of 87 patients at month 6, and 32 (46·4%, 34·3-58·8) of 69 patients at month 12; partial response was observed in an additional 43 (35·5%, 27·0-44·8) patients at month 3, 23 (26·4%, 17·6-37·0) at month 6, and 13 (18·8%, 10·4-30·1) at month 12. BVAS dropped from 3·0 (IQR 2·0-8·0) at baseline to 0·0 (0·0-2·0) at months 3 and 6, and to 0·0 (0·0-1·0) at month 12. The proportion of patients with systemic manifestations, active peripheral neurological disease, ear, nose, and throat involvement, and pulmonary involvement decreased, with an improvement in lung function tests. Six patients relapsed after having a complete response. The oral prednisone (or equivalent) dose decreased from 10·0 mg/day (5·0-12·5) at baseline to 5·0 mg/day (3·6-8·5) at month 3 (p<0·01), to 5·0 mg/day (2·5-6·3) at month 6, and to 2·5 mg/day (0·0-5·0) at month 12 (p<0·0001). 19 (16%) of 121 patients had adverse events and 16 (13%) discontinued benralizumab. These data suggest that benralizumab could be an effective treatment for EGPA in real-life clinical practice. Further clinical trials are required to confirm the efficacy of benralizumab in patients with a higher baseline disease activity. None.

Real-Life Efficacy of Tofacitinib in Various Situations in Ulcerative Colitis: A Retrospective Worldwide Multicenter Collaborative Study.

Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC. This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed. A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported. TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found.

Responsiveness and Minimum Clinically Important Difference in Patient-Reported Outcome Measures Among Patients With Psoriatic Arthritis: A Prospective Cohort Study.

To determine the responsiveness to therapy and minimum clinically important improvement (MCII) for patient-reported outcome measures in psoriatic arthritis (PsA) and to examine the impact of baseline disease activity on the ability to demonstrate change. A longitudinal cohort study was performed within the PsA Research Consortium. Patients completed several patient-reported outcomes, including the Routine Assessment of Patient Index Data, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Psoriatic Arthritis Impact of Disease 12-item (PsAID12) questionnaire, and others. The mean change in the scores between visits and standardized response means (SRMs) were calculated. The MCII was calculated as the mean change in score among patients who reported minimal improvement. SRMs and MCIIs were compared among subgroups with moderate to highly active PsA and those with lower disease activity. Among 171 patients, 266 therapy courses were included. The mean ± SD age was 51 ± 13.8 years, 53% were female, and the mean swollen and tender joint counts were 3 and 6, respectively, at baseline. SRMs and MCII for all measures were small to moderate, although greater among those with higher baseline disease activity. BASDAI had the best SRM overall and for less active PsA, and the clinical Disease Activity of PsA (cDAPSA) and PsAID12 were best for those with higher disease activity. SRMs and MCII were relatively small in this real-world population, particularly among those with lower disease activity at baseline. BASDAI, cDAPSA, and PsAID12 had good sensitivity to change, but selection for use in trials should consider the baseline disease activity of patients to be enrolled.

P183 Disease activity, comorbidities and functional status predict treatment response to biologic and targeted synthetic disease-modifying anti-rheumatic drugs in psoriatic arthritis

Abstract Background/Aims Much discussion surrounds the optimal therapeutic treatment plan for biologic and targeted synthetic disease modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) when treating psoriatic arthritis (PsA). The current study aims to identify predictors of treatment response among PsA patients initiating bDMARD/tsDMARD treatment, focusing on disease activity, functional status (Health Assessment Questionnaire, HAQ), and comorbidities. Methods The systematic review of clinical trials and observational studies used Medline, Embase and Cochrane databases. Eligible studies included full text papers with quantitative estimates of effect (or data to allow these to be computed). Papers also required a validated assessment of treatment response i.e., Minimal Disease Activity (MDA), or some other marker of treatment response such as treatment continuation. Case reports and conference abstracts were excluded. Results From 2824 articles identified, 27 were included. Across these, &amp;gt;15 different outcomes were used, and measured at &amp;gt; 10 different timepoints. There was consistent evidence to suggest that higher baseline disease activity was associated with a reduction in the likelihood of treatment response, see Table 1. Some studies reported up to 20% reduction in odds of LDA at 6 months associated with each 1 unit increase in DAPSA. Others demonstrated that patients with a high DAS28 (&amp;gt;3.2) experienced over a 90% reduction in the odds of MDA at 12 weeks. Eleven studies (from 15) demonstrated a significant association between baseline function and odds of treatment response. Each 1 unit increase in HAQ-DI decreased the odds of a good EULAR response at 3 months by up to 66%. The presence of comorbidities was also consistently associated with a decrease in treatment response. Studies showed that the presence of comorbidities at baseline lessened the odds of MDA at 6 months by up to 80%. Others reported that comorbidities were associated with a reduction in the odds of 5 year treatment persistence by up to 40%. Conclusion This review shows clear evidence of reduced bDMARD/tsDMARD response in PsA among patients with disease activity, poor function, and comorbidities. Clinicians should be aware of the reduced chances of treatment success and should consider early review of therapy, to consider whether treatment escalation or switching is required. Disclosure C. Addae-Kyereme: None. S. Lembke: None. G.J. Macfarlane: None. G.T. Jones: None.

P605 Real life efficacy of tofacitinib in different situation in ulcerative colitis: a retrospective worldwide multicentre collaborative study

Abstract Background The orally administered small molecule drug pan-Jak inhibitor tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC), however, available real world studies are limited by the cohort size. In addition, TFB may also be efficacious in patients with acute severe colitis (ASUC) as a rescue therapy. We aimed to conduct an international cohort study, to investigate the efficacy and safety of TFB in patients with moderate to severe colitis and ASUC. Methods This was a retrospective, international multi-centre, cohort study including 23 tertiary referral centres. UC patients with at least 6 weeks of TFB treatment were included. Physicians categorized the indication as rescue therapy (RT) and chronic activity (CA). Baseline demographic and clinical data, clinical/endoscopic activity indexes, laboratory parameters (including CRP, faecal calprotectin, liver enzymes, lipids, iron homeostasis), adverse events, and hospitalization/colectomy rates were collected at w0, w2-6, w8-14, w22-30 and w48-56 intervals. Steroid-free remission, colectomy rates, primary non-response (PNR) and loss-of response (LOR) rates, and safety was studied. Results A total of 391 UC patients (mean age: 39.2±14.1 years, male/female ratio 208/183; mean follow-up period 33.7±18.1 weeks) were included. 107 patients (27.4%) received TFB as a rescue therapy. Most of the patients received it as a third line treatment (37.4%). Steroid-free remission (SFR) rates were 21.3% (RT: 25.0%, CA: 22.3%) at w14, and 40.1% (RT: 32.5%, CA: 42.2%) at w52. In total, baseline pMayo (OR: 0.856; p=0.007) was negatively associated with w12 SFR, while line of treatment (OR: 0.749; p=0.047) and age (OR: 1.022; p=0.038) influenced the w52 SFR in the CA group. The w12 colectomy rate was 5.1%, and no difference was observed between groups (RT: 8.5%; CA: 3.8%), however, w52 colectomy rate was higher in the RT group (19.2% compared to 5.9%; p&amp;lt;0.001). Line of treatment (OR: 1.66; p=0.036) and age (OR: 0.94; p=0.005) were associated as well with w52 colectomy rate. Mucosal healing (eMayo≤1) rate increased from 3.9% to 43.0% (p&amp;lt;0.001). PNR rate was 22.5% and LOR 54.4%. In total, 67 adverse events (17.1%) were reported, and 17.9% of them were resulted in cessation of the treatment. Thromboembolic event was reported in 1 case, however, this patient had concomitant malignancy. Conclusion TFB is effective in both moderate to severe UC, and in patients with ASUC as a rescue therapy. TFB treatment resulted in high rates of SFR and mucosal healing in short- and long term even after anti-TNF and vedolizumab failure. Higher baseline disease activity and number of previous biological therapies negatively influenced efficacy. Serious adverse events were rare.

Patient Disease Trajectories in Rheumatoid Arthritis Patients Treated with Baricitinib 4-mg in FourPhase 3 Clinical Studies.

We sought to identify and compare treatment response groups based on individual patient responses (rather than group mean response) over time on the Clinical Disease Activity Index (CDAI) for rheumatoid arthritis (RA), in patients treated with baricitinib 4-mg in 4phase 3studies. Trajectory subgroups were identified within each study using growth mixture modeling. Following grouping, baseline characteristics and disease measures were summarized and compared. In each study, three response trajectories were identified. In the three studies of patients naïve to biological disease-modifying anti-rheumatic drugs (bDMARDs) patients had, on average, high disease activity, as measured by CDAI. In these studies, a group of rapid responders (65-71% of patients) had the lowest baseline CDAI scores and achieved mean CDAI ≤ 10 by week 16. Gradual responders (10-17%) had higher baseline CDAI, but generally achieved low disease activity (CDAI ≤ 10) by week 24. A group of partial responders (18-22%) had higher baseline CDAI and did not achieve mean CDAI ≤ 10. In bDMARD-experienced patients, the subgroups were rapid responders, who achieved mean CDAI ≤ 10 (42% of patients); partial responders, with mean CDAI decrease of ~ 15 points from baseline (42% of patients); and limited responders (15% of patients). Changes in modified total sharp score (mTSS; assessed only in biologic-naïve patients) were below the smallest detectable difference at 24/52weeks for > 90% of patients in each group, excepting partial responders in RA-BEGIN (≥ 75% no detectable change). In patients receiving baricitinib 4-mg, lower baseline CDAI was generally associated with rapid response, while higher baseline CDAI scores were generally seen for patients who either reached treatment targets more gradually, or who had a partial or limited response. Maintenance of response was observed with continued baricitinib treatment in all response groups and generally included maintenance of mTSS.

Pain Mechanisms Associated With Disease Activity in Patients With Rheumatoid Arthritis Treated With Disease-Modifying Antirheumatic Drugs: A Regression Tree Analysis.

Although pain affects the assessment of disease activity in patients with rheumatoid arthritis (RA), pain is not always directly related to peripheral joint inflammation. Peripheral and central nervous system regulatory mechanisms also affect pain perception. We used regression tree methodology to identify mechanisms most predictive of disease activity after disease-modifying antirheumatic drug (DMARD) treatment. Disease activity was evaluated using the Disease Activity Score in 28 joints (DAS28) in 176 patients with RA, before and after starting a DMARD. Quantitative sensory testing (QST), including pressure pain thresholds (PPTs), temporal summation, and conditioned pain modulation (CPM), were used to assess pain mechanisms. Regression tree methodology was used to determine the QST modalities most predictive of DAS28 after DMARD treatment. This analysis identified 4 groups defined by baseline DAS28 category and either knee PPT (a combined measure of peripheral and central nervous system dysregulation) or CPM (a measure of descending pain inhibition). Among patients starting with low/moderate disease activity, lower knee PPT (PPT ≤ 4.65 kgf) most strongly predicted higher posttreatment disease activity (group 1 mean DAS28 2.8 [SD 1.0] vs group 2 mean DAS28 3.5 [SD 1.0]). Among patients starting with high baseline disease activity, less efficient descending pain modulation (CPM ≤ 1.55) most strongly predicted higher posttreatment disease activity (group 3 mean DAS28 3.4 [SD 1.4] vs group 4 mean DAS28 4.6 [SD 1.1]). These results highlight the importance of identifying and treating aberrant peripheral and central pain regulation in patients with RA starting or switching DMARD therapy.

Disease trajectory of SLE clinical endpoints and covariates affecting disease severity and probability of response: Analysis of pooled patient-level placebo (Standard-of-Care) data to enable model-informed drug development.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems. Many investigational agents have failed or shown only modest effects when added to standard of care (SoC) therapy in placebo-controlled trials, and only two therapies have been approved for SLE in the last 60 years. Clinical trial outcomes have shown discordance in drug effects between clinical endpoints. Herein, we characterized longitudinal disease activity in the SLE population and the sources of variability by developing a latent disease trajectory model for SLE component endpoints (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI], Physician's Global Assessment [PGA], British Isles Lupus Assessment Group Index [BILAG]) and composite endpoints (Systemic Lupus Erythematosus Responder Index [SRI], BILAG-based Composite Lupus Assessment [BICLA], and Lupus Low Disease Activity State [LLDAS]) using patient-level historical SoC data from nine phase II and III studies. Across all endpoints, in predictions up to 52 weeks from the final disease trajectory model, the following baseline covariates were associated with a greater decrease in SLE disease activity and higher response to placebo + SoC: Hispanic ethnicity from Central/South America, absence of hypocomplementemia, recent SLE diagnosis, and high baseline disease activity score using SLEDAI and BILAG separately. No discernible differences were observed in the trajectory of response to placebo + SoC across different SoC medications (antimalarial and immunosuppressant such as mycophenolate, methotrexate, and azathioprine). Across all endpoints, disease trajectory showed no difference in Asian versus non-Asian patients, supporting Asia-inclusive global SLE drug development. These results describe the first population approach to support a model-informed drug development framework in SLE.

Pulmonary hypertension in juvenile-onset systemic lupus erythematosus: a case series.

Systemic lupus erythematosus (SLE) is a rare multisystem autoimmune disorder with a variable clinical phenotype. Pulmonary hypertension (PHTN) is a recognised (and not uncommonly asymptomatic) complication of the condition with an associated poor prognosis in adults. It is relatively rare in juvenile-onset SLE (JSLE). We present a retrospective descriptive case series of four female children aged 4 to 15 years at presentation of JSLE and aged 8 to 27 years at time of diagnosis of PHTN from the United Kingdom. All cases were identified through the UK JSLE Cohort Study. Of 665 children with JSLE in the UK cohort study to date (data from 2006-2020), four (0.6%) were identified as having PHTN. 3/4 of the PHTN cases presented with cardiovascular symptoms and / or signs at presentation.3/4 were treated with Rituximab and had a good long-term outcome. Shared clinical features include high baseline disease activity scores. JSLE has a high associated cardiovascular morbidity and mortality and early identification of treatable complications such as PHTN is vital. We suggest that children with high baseline disease activity scores and those presenting with cardiovascular symptoms and signs are most likely to have concurrent PHTN. Routine echocardiography is an effective screening tool and should be used as part of a standard diagnostic work-up.

Serum Fatty Acid Profiles Are Associated with Disease Activity in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort.

Background: Long-chain omega-3 and omega-6 fatty acids (n-3, n-6 FAs) may modulate inflammation and affect the risk of developing rheumatoid arthritis (RA). However, whether n-3/n-6 FA status affects RA after disease onset is unknown. This study aimed to assess whether FA profiles are independently associated with disease activity in a large prospective cohort of patients with early RA. Methods: Baseline serum FAs were quantified in 669 patients in the ESPOIR cohort. Principal component analysis identified three serum FA patterns that were rich in n-7–9, n-3 and n-6 FAs (patterns ω7–9, ω3 and ω6), respectively. The association of pattern tertiles with baseline variables and 6-month disease activity was tested using multivariable logistic regression. Results: Pattern ω3 was associated with low baseline and pattern ω6 with high baseline C-reactive protein level and disease activity. Both patterns ω3 and ω6 were associated with reduced odds of active disease after 6 months of follow-up (pattern ω3: odds ratio, tertile three vs. one, 0.49 [95% CI 0.25 to 0.97] and pattern ω6: 0.51 [0.28 to 0.95]; p = 0.04 and 0.03, respectively). Conclusions: In a cohort of early RA patients, a serum lipid profile rich in n-3 FAs was independently associated with persistently reduced disease activity between baseline and 6-month follow-up. An n-6 FA profile was also associated with lower 6-month disease activity.

Distinct patterns of disease activity over time in patients with active SLE revealed using latent class trajectory models

BackgroundSystemic lupus erythematosus (SLE) is a heterogeneous systemic autoimmune condition for which there are limited licensed therapies. Clinical trial design is challenging in SLE due at least in part to imperfect outcome measures. Improved understanding of how disease activity changes over time could inform future trial design. The aim of this study was to determine whether distinct trajectories of disease activity over time occur in patients with active SLE within a clinical trial setting and to identify factors associated with these trajectories.MethodsLatent class trajectory models were fitted to a clinical trial dataset of a monoclonal antibody targeting CD22 (Epratuzumab) in patients with active SLE using the numerical BILAG-2004 score (nBILAG). The baseline characteristics of patients in each class and changes in prednisolone over time were identified. Exploratory PK-PD modelling was used to examine cumulative drug exposure in relation to latent class membership.ResultsFive trajectories of disease activity were identified, with 3 principal classes: non-responders (NR), slow responders (SR) and rapid-responders (RR). In both the SR and RR groups, significant changes in disease activity were evident within the first 90 days of the trial. The SR and RR patients had significantly higher baseline disease activity, exposure to epratuzumab and activity in specific BILAG domains, whilst NR had lower steroid use at baseline and less change in steroid dose early in the trial.ConclusionsLongitudinal nBILAG scores reveal different trajectories of disease activity and may offer advantages over fixed endpoints. Corticosteroid use however remains an important confounder in lupus trials and can influence early response. Changes in disease activity and steroid dose early in the trial were associated with the overall disease activity trajectory, supporting the feasibility of performing adaptive trial designs in SLE.

AB0479 LONGTERM RETENTION RATE OF CERTOLIZUMAB PEGOL IN AXIAL SPONDYLOARTHRITIS IS HIGHER: DATA FROM TURKBIO

Background:Choosing the best treatment strategy for a patient is one of the most difficult issues in modern rheumatology, as there are various factors affecting drug therapy in chronic diseases, such as efficacy, safety, and compliance. Physicians take care of long-term retention rate and responses for discontinuation of candidate drug.Objectives:The purpose of this study to assess the drug survival of certolizumab pegol (CZP) in patients with axial spondyloarthritis (ax-SpA) and to identify the predictors and reasons for discontinuation.Methods:Data on patient characteristics, demographics, diagnosis, duration of disease, treatment and outcomes have been collected since 2011 in Turkish Biologic (TURKBIO) Registry. By the end of December 2020, 410 ax-SpA patients received CZP and were included. Kaplan Meier plot was used for drug survival analysis. Cox regression analysis was performed to evaluate the predictor associated with drug survival.Results:During the median 54 months follow-up, 92 (22.4%) patients discontinued the CZP treatment. The reasons for discontinuation: ineffectivity was 58.7% (n=54), adverse events was 6.5%, pregnancy was 3.3% and surgery was 4.3%. The baseline characteristics of patients continue with CZP and discontinuation due to ineffectiveness were shown in the Table 1. Patients who discontinued CZP had higher HAQ, BASFI and BASDAI values. Moreover, they were more co-treated with NSAIDs and csDMARDs. At the month 36, retention rate of CZP was 71.5% in patients with ax-SpA (Figure 1).Conclusion:Real life experience from this nationwide TURKBIO registry show higher long-term retention rate of CZP in ax-SpA. Higher baseline disease activity and functional limitation predict discontinuation of CZP. Adding NSAIDs and csDMARDs to the treatment of the patient with poor prognosis cannot increase retention rates.Figure 1Drug survival of CZP in patients with Ax-SpATable 1.Baseline characteristics of ax-SpA patients who continue and discontinue CZPAll patients (n=410)Continue to CZP (n=318)Discontinue to CZP* (n=54)pFemales, n (%)185 (49,7)157 (49,4)28 (51,9)0,736Age, years42 (34-49)41 (34-49)45 (34-54)0,064Symptom duration, years11 (7-17)11 (6-16)12 (8,5-20)0,054HLA-B27, n (%)150 (63,8)129 (64,5)21 (60)0,609Previous bDMARDs, n (%)Adalimumab54 (14,5)42 (13,2)12 (22,2)0,082Etanercept53 (14,2)40 (12,6)13 (24,1)0,025Golimumab11 (3)7 (2,2)4 (7,4)0,060Infliximab39 (10,5)35 (11)4 (7,4)0,425Co-treated drugs, n (%)NSAID206 (55,4)169 (53,1)37 (68,5)0,036Methotrexate35 (9,4)22 (6,9)13 (24,1)&lt;0,001Sulphasalazine61 (16,4)40 (12,6)21 (38,9)&lt;0,001Leflunomide5 (1,3)2 (0,6)3 (5,6)0,023ESH, mm/h21,5 (10-37)21 (10-37)23 (10-34)0,999CRP, mg/dl7 (3-20)7 (3-20)7 (3-22)0,727HAQ0,63 (0,25-0,94)0,5 (0,25-0,88)0,75 (0,38-1,25)0,009BASFI21 (7-45)20,5 (6-41)31 (13-58)0,011BASDAI30,5 (13-52)30 (12-50)43 (23-61,5)0,002ASDAS2,7 (1,8-3,7)2,7 (1,8-3,6)2,9 (2,3-4)0,062*Discontinue due to ineffectivity.

OP0125 TOFACITINIB IN RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE: EFFICACY AND SAFETY ANALYSIS FROM TREASURE REAL-LIFE DATA

Background:Beyond the joints, rheumatoid arthritis (RA) may affect lungs. Especially the involvement of the paranchyme, RA-associated interstitial lung disease (RA-ILD), is a major cause of mortality and morbidity. Tofacitinib, an oral JAK 1/3 inhibitor, has been used increasingly in the management of rheumatoid arthritis (RA) in recent years. Recently, a couple of animal and human studies reported promising results (1).Objectives:To assess the real-life efficacy and safety of tofacitinib in patients with RA-ILD in TReasure registry.Methods:This is a multicenter, observational study included RA patients with ILD diagnosis based on the HRCT images of the lungs, and were followed in 8 different centers participated in the TReasure database. Demographic data and patients’ characteristics regarding RA and RA-ILD at the visit in which tofacitinib was initiated and for the last follow-up visit under tofacitinib were recorded. Using the present study cohort, the RA patients with ILD receiving tofacitinib were compared with those without ILD receiving tofacitinib (controls) in terms of the general and disease-related characteristics and data of concomitant DMARD use. To evaluate retention rates of tofacitinib and reasons for discontinuation, data of the patients with RA-ILD in this study cohort were compared with the data of RA patients without ILD who were followed in Hacettepe University (major contributor of the TReasure registry). This research was funded by Pfizer.Results:A total of 47 RA patients with RA-ILD and a control group of 387 patients without ILD were included. The RA patients with ILD receiving tofacitinib were mostly male, older, and had higher baseline disease activity as compared with those without ILD (Table). The ILD pattern was known in 44 (93.6%) of 47 RA-ILD: 16 (36.3%) had UIP, 24 (54.5%) had NSIP, and 4 (9.1%) had airway disease. While 15 (31.9%) of the patients was asymptomatic, most common initial symptom was shortness of breath (in 14 (29.7%) patients). 18 patients had pre- and post-treatment FVC% and FEV1% values (with a median of 12 (9-19) months). Mean FEV1%; 82.1 vs. 82.8 (pre and post-treatment, respectively, p=0.079), mean FVC%; 79.8 vs. 82.8 (pre and post-treatment, respectively, p=0.014). To evaluate retention rates and reasons for discontinuation, 47 RA-ILD and 239 RA patients without ILD were analyzed. Retention rates were similar (p=0.21, log-rank) (Figure). Most common cause of tofacitinib discontinuation in RA-ILD group was infections (5 (25%) patients). Follow-up durations under tofacitinib were 15 (7-32) and 11 (4-24) months in ILD + and – groups, respectively. The rate of drug discontinuation due to infection in the RA patients with and without ILD was 6.3 per 100 patient-years and 2.4 per 100 patient-years, respectively.Table 1.Characteristics of the RA patients with and without ILD under tofacitinibVariablesRA-ILD(+) n=47RA-ILD(-) n=387pMale sex20 (42.6)69 (17.8)&lt;0.001Age, years64 (57-69)56 (46-64)&lt;0.001Disease duration for RA, months128 (78-212)110 (64-183)0.171Smoking statusNever smoker26 (55.3)211 (56.4)0.259 Current&amp;Ex-smoker19 (44.7)163 (43.6)RF (+)36 (78.3)249 (68.8)0.187Anti-CCP (+)30 (65.2)196 (61.6)0.640RF positive or CCP (+)41 (87.2)242 (76.3)0.094Presence of comorbidity33 (70.2)203 (52.5)0.021DAS-28 before tofacitinib5.4 (4.6-6.22)4.36 (3.22-5.58)&lt;0.001ESR before tofacitinib, mm/h38 (19-73)29 (17-45)0.029CRP before tofacitinib6.75 (1.63-24)9.95 (4.18-25.1)0.065Follow-up duration under tofacitinib15 (7-32)7 (3-12)&lt;0.001Figure 1.Tofacitinib retention rates in the RA patients with and without ILDConclusion:In majority of patients, pulmonary functions remained stable during follow-up. Tofacitinib seems as a promising option for RA-ILD. High rate of discontinuation due infections was observed in RA-ILD patients under tofacitinib; however, it should be kept in mind that RA-ILD patients were older than RA patients without ILD.

Circulating miR-145 as a marker of therapeutic response to anti-TNF therapy in patients with ankylosing spondylitis

Circulating miRNAs appear promising therapeutic and prognostic biomarkers. We aimed to investigate the predictive value of circulating miRNAs on the disease outcome following anti-TNF therapy in patients with ankylosing spondylitis (AS). Our study included 19 AS patients assessed at baseline (M0), after three (M3) and twelve months (M12) of therapy. Total RNA was isolated from plasma. A comprehensive analysis of 380 miRNAs using TaqMan Low Density Array (TLDA) was followed by a single assay validation of selected miRNAs. All AS patients had high baseline disease activity and an excellent response to anti-TNF therapy at M3 and M12. TLDA analysis revealed the dysregulation of 17 circulating miRNAs, including miR-145. Single assay validation confirmed that miR-145 is significantly downregulated at M3 compared to baseline. The decrease in the levels of miR-145 from M0 to M3 negatively correlated with the change in BASDAI from M0 to M3; and positively correlated with disease activity improvement from M3 to M12 as per BASDAI and ASDAS. The predictive value of the early change in miR-145 and levels of miR-145 at M3 were further validated by Receiver operating curves analysis. We show thatthe early change in circulating miR-145 may be a predictor for the future outcome ofAS patients treated with TNF inhibitors. Patients with a more significant decrease in miR-145 levels may show further significant improvement of disease activity after 12 months. Monitoring the expression of miR-145 in plasma in AS patients may, therefore, influence our therapeutic decision-making.

Predictors of radiographic erosion and joint space narrowing progression in patients with early rheumatoid arthritis: a cohort study

BackgroundRadiographic damage in rheumatoid arthritis (RA) includes erosions and joint space narrowing (JSN). Different mechanisms may underlie their development. The objective of this study was to evaluate predictors of these entities separately.MethodsConsecutive early RA patients (symptom duration ≤12 months) from a defined area (Malmö, Sweden) recruited during 1995–2005 were investigated. Radiographs of hands and feet were scored by a trained reader according to the modified Sharp-van der Heijde score. Fat mass and lean mass distribution were measured at baseline using dual energy x-ray absorptiometry. Potential predictors of erosion and JSN progression from inclusion to the 5-year follow-up were evaluated.ResultsTwo hundred and thirty-three patients were included. Radiographs at baseline and 5 years were available for 162 patients. The median (interquartile) progression of erosion and JSN scores were 4 (0–8) and 8 (1–16), respectively. Rheumatoid factor (RF) was a robust significant predictor of both erosion and JSN score progression. In adjusted analyses, anti-CCP antibodies predicted erosions while the erythrocyte sedimentation rate was predictive of both outcomes. Smoking and high baseline disease activity (DAS28 > 5.1) predicted progression of erosions. Baseline erosion score was associated with progression of both erosion and JSN progression, while baseline JSN score was predictive only of the progression of JSN. Overweight/obesity (BMI ≥ 25 kg/m2) was a significant negative predictor of JSN score progression (β = − 0.14, p = 0.018, adjusted for RF, age, baseline JSN score) also when additionally adjusting for ever smoking (p = 0.041). Among female patients, this effect was observed in those of estimated post-menopausal age (> 51 years), but not in younger women. The truncal to peripheral fat ratio was associated with less JSN score progression in women, but not in men.ConclusionsOverweight RA patients had less JSN progression, independent of smoking status. This effect was seen in particular among older women (mainly post-menopausal), but not younger. Truncal fat was associated with less JSN progression in female patients. Smoking predicted erosion progression, and erosions may precede JSN. BMI and fat distribution may influence cartilage damage in early RA and might be related to hormonal factors.

Reopening Schools in the Pandemic Did Not Increase COVID-19 Incidence and Mortality in Brazil

Background: School closures due to COVID-19 have left 1.6 billion students around the world without in-person classes for a prolonged period of time. To date, no study has documented whether reopening schools in developing countries during the pandemic causally increased aggregate COVID-19 incidence and mortality with appropriate counterfactuals.Methods: We take advantage of the fact that 131 municipalities in São Paulo State, Brazil, reopened schools for in-person activities between October and December 2020, to estimate the causal effects of school reopening on municipal-level COVID-19 effective potential growth and deaths. We estimate treatment effects through a differences-in-differences strategy, comparing how outcomes evolved between municipalities that reopened schools and all others, before and after school reopening. We also estimate heterogeneous treatment effects by local characteristics. Last, we estimate the effects of school reopening on a local mobility index to shed light on the mechanisms behind its impacts on disease activity.Findings: We find that school reopening did not increase COVID-19 incidence or mortality on average, up to 12 weeks after reopening. The counterfactual is critical for our conclusions: comparing only municipalities that reopened schools before and after reopening would lead us to conclude the opposite. Reopening schools did not affect disease activity even in poorer municipalities, in those with low-quality school infrastructure, with higher senior population share, or with higher baseline disease activity. We also find no effects of school reopening on the local mobility index.Interpretation: While keeping schools open during the pandemic could still increase risks for school staff and students’ families, our findings suggest that it did not contribute to the aggregate disease activity. This was the case not only because schools typically represent only a small fraction of the overall municipal population, but also because counterfactual mobility during the pandemic was already substantial even in the absence of in-person classes – making the marginal health benefits of keeping schools closed negligible in the aggregate.

Reopening Schools in the Pandemic Did Not Increase COVID-19 Incidence and Mortality in Brazil

Background:&amp;nbsp;School closures due to Covid-19 have left 1.6 billion students around the world without in-person classes for a prolonged period of time.To date, no study has documented whether reopening schools in developing countries during the pandemic causally increased aggregate Covid-19 incidence and mortality with appropriate counterfactuals. Methods: We take advantage of the fact that 131 municipalities in S&atilde;o Paulo State, Brazil, reopened schools for in-person activities between October and December 2020, to estimate the causal effects of school reopening on municipal-level Covid-19 effective potential growth and deaths. We estimate treatment effects through a differences-in-differences strategy, comparing how outcomes evolved between municipalities that reopened schools and all others, before and after school reopening. We also estimate heterogeneous treatment effects by local characteristics. Last, we estimate the effects of school reopening on a local mobility index to shed light on the mechanisms behind its impacts on disease activity.\ Findings: We find that school reopening did not increase Covid-19 incidence or mortality on average, up to 12 weeks after reopening. The counterfactual is critical for our conclusions: comparing only municipalities that reopened schools before and after reopening would lead us to conclude the opposite. Reopening schools did not affect disease activity even in poorer municipalities, in those with low-quality school infrastructure, with higher senior population share, or with higher baseline disease activity. We also find no effects of school reopening on the local mobility index. Interpretation: While keeping schools open during the pandemic could still increase risks for school staff and students&rsquo; families, our findings suggest that it did not contribute to the aggregate disease activity. This was the case not only because schools typically represent only a small fraction of the overall municipal population, but also because counterfactual mobility during the pandemic was already substantial even in the absence of in-person classes &ndash; making the marginal health benefits of keeping schools closed negligible in the aggregate. Funding: Research funded by the Inter-American Development Bank. Declaration of Interest: GL and OLN received fees from the Inter-American Development Bank (IADB) for the design of this study. JC is an IADB staff member. CAB declares no competing interests.

Relation Between Fatigue and ACR Response in Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitor Therapy: A Population-based Cohort Study.

The objective of this population-based cohort study was to investigate the association between fatigue with disease activity and drug survival in patients with psoriatic arthritis (PsA) receiving their first tumor necrosis factor inhibitor (TNFi). Data on patient characteristics, disease activity, and drug survival were obtained from the DANBIO database on all patients with PsA from 2006 through 2015. Information on comorbidities was obtained through linkage with the Danish National Patient Registry. A total of 880 patients were eligible for analyses. Patients with upper median fatigue scores had statistically significant higher disease activity measures (Disease Activity Score in 28 joints based on C-reactive protein), pain, and Health Assessment Questionnaire (HAQ) scores; tender joint counts; comorbidities (Charlson Comorbidity Index ≥ 2); and current smoking status at baseline compared to patients with lower median fatigue scores (P < 0.05). In the upper median fatigue group, fewer patients achieved American College of Rheumatology (ACR) responses and improvements in visual analog scale (VAS) fatigue compared to patients in the lower median fatigue group. Kaplan-Meier curves showed shorter drug survival in patients in the upper median fatigue group compared with the lower median fatigue group at 6-month follow-up. Fatigue remains a dominating symptom after TNFi treatment, and is associated with higher baseline disease activity, pain, and HAQ scores; more comorbidities; and increased risk of TNFi treatment discontinuation in a cohort of Danish patients with PsA. The agreement between ACR and VAS fatigue responses is weak to moderate, suggesting heterogeneity between experienced fatigue and joint inflammation.

Descriptive Comparisons of the Effect of Apremilast and Methotrexate Monotherapy in Oligoarticular Psoriatic Arthritis: The Corrona Psoriatic Arthritis/Spondyloarthritis Registry Results.

Therapeutic response was evaluated among new apremilast, methotrexate (MTX), or biologic disease-modifying antirheumatic drug (bDMARD) initiators with oligoarticular psoriatic arthritis (PsA). Patients with oligoarticular PsA in the Corrona PsA/Spondyloarthritis Registry initiating treatment with apremilast, MTX, or bDMARD, and completing 6-month follow-up were included. In total, 150 patients initiated monotherapy (apremilast: n = 34; MTX: n = 15; bDMARD: n = 101). Apremilast initiators had higher baseline disease activity than MTX initiators. At follow-up, apremilast initiators experienced numerically greater disease activity improvements than MTX initiators and similar improvements to bDMARD initiators. Findings suggest apremilast monotherapy is an effective option for patients with oligoarticular PsA.