CDAI Score Research Articles

Clinical and ultrasound optimization in rheumatoid arthritis for patients in sustained remission, can it work as a new optimization tool?

Some studies have noted that scores relying solely on clinical values to evaluate remission in rheumatoid arthritis (RA) may miss subclinical inflammation, which can lead to exacerbations when therapy is reduced. This opens the possibility of supporting clinical evaluation with imaging studies, one of which is ultrasound (US) evaluation, since it is an accessible tool. Therefore, we have decided to design a study to try to demonstrate the usefulness of US as a complementary measure for the decision-making process in determining the optimization of therapy in patients with RA. A multicenter, blinded, randomized, prospective study was conducted in RA patients meeting 2010 ACR/EULAR criteria for sustained remission by DAS28-ESR, with concomitant CDAI/SDAI evaluation. Patients were classified into clinical and ultrasound groups, with treatment remission based on DAS28 or grayscale synovitis/Doppler values. Ultrasound assessments included grayscale (GS) and power Doppler (PD) for joints (A) and tendons (T). A 12months follow-up was performed, with a subset analyzed at both 18 and 24months. Exacerbation criteria: DAS28-ESR rise > 1.2 or CDAI/SDAI > 16. Across all centers, 78 patients were initially recruited, but only 46 completed the 12-month follow-up, with 28 undergoing further evaluation at 24months. The average baseline DAS28 scores were 1.85 for the clinical group and 1.80 for the ultrasound group. During the study, 18 patients experienced disease exacerbation based on DAS28 score elevation, with 10 in the clinical group and 8 in the ultrasound group. Seven patients experienced disease exacerbation based on CDAI score elevation, all of whom were included in the clinical group. Eight patients showed disease exacerbation based on SDAI score elevation, all in the clinical group. We have demonstrated the utility of ultrasound when optimizing management of rheumatoid arthritis patients. In our patient cohort, ultrasound helps to reduce the number of exacerbations using the SDAI/CDAI index. We highlight the limitations of current assessment methods that rely solely on clinical evaluation, underscore the potential significance of evaluating subclinical synovitis, and emphasize the role of ultrasound as an objective tool in guiding therapy decisions. Our study offers valuable insights for optimizing treatment strategies in RA patients and improving their long-term outcomes.

People with osteoarthritis have a higher component of neuropathic pain as compared to those with rheumatoid arthritis: A cross-sectional study.

Neuropathic pain may be present in a proportion of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Its presence may lead to the requirement of altered management approaches in these conditions. This study investigated the prevalence of neuropathic pain in OA as compared to that in RA. Patients with OA and RA were included cross-sectionally if they had no other known neuropathic disorder. The PainDETECT questionnaire was used to assess neuropathic pain. WOMAC and CDAI scores were used to assess disease severity in OA and RA respectively. 69 patients with OA with a mean WOMAC score of 53.30 ± 16.39 and 98 patients with RA with a mean CDAI of 25.48 ± 16.99 were compared. The median PainDETECT score for OA was 13 (0-30) and RA was 5 (0-37) [p<0.001]. 15 patients with OA and six patients with RA were highly likely to have neuropathic pain, while 15 patients with OA and 30 patients with RA were classified as possibly having neuropathic pain. Thus, the proportion of patients free from neuropathic pain was higher in the RA group (63.3%) than in the OA group (39.1%) [p = 0.003]. Both the prevalence and the severity of neuropathic pain were significantly higher in OA than in RA. These findings suggest that neuropathic pain is an important factor in OA, as in RA, and must be considered in management as well as in future research in both these conditions.

Impact of Infliximab Biosimilar (Ixifi®) Trough Levels on Disease Activity and Inflammatory Markers in Iraqi Rheumatoid Arthritis Patients

Background: Rheumatoid arthritis is an autoimmune inflammatory condition that impacts the small and larger joints. Ixifi® is a biosimilar medication derived from infliximab that exclusively targets Tumor Necrosis Factor-α. Serum Ixifi® trough concentration is necessary to manage disease activity in rheumatoid arthritis. Objective: Assess the impact of the Ixifi® trough level on disease activity and inflammatory biomarkers. Methods: A cross-sectional observational study was undertaken at Baghdad Teaching Hospital, involving forty-two patients diagnosed with rheumatoid arthritis according to ACR/EULAR 2010 criteria. After 3 months after initiating therapy with Ixifi®, the serum concentrations of Ixifi®, as well as CDAI, ESR, and CRP biomarkers, were measured. Results: After 3 months of therapy with Ixifi®, the patients in the remission group had a higher concentration of Ixifi® compared to the mild, moderate, and severe disease activity groups. Ixifi® trough level in remission was 5.45 µg/ml, while in mild, moderate, and severe groups, it was 3.575 µg/ml, 2.2 µg/ml, and 0.66 µg/ml, respectively. The CDAI scores were in the severe group (26.0), moderate group (19.0), mild group (7.0), and remission group (2.0). Furthermore, the findings indicate an inverse correlation between the Ixifi® trough level and both ESR and CRP. Conclusions: A drop in Ixifi® levels leads to an increase in disease severity and inflammation, while high concentrations of Ixifi® decrease disease activity, ESR, and CRP.

Upper Gastrointestinal Involvement in Crohn's Disease as an Independent Predictor of New-Onset Strictures: Insights from an Extensive Retrospective Cohort Analysis.

Crohn's Disease (CD) can affect the entire gastrointestinal tract, including the upper sections (UGI), which is often overlooked, especially in Asian populations. There's a notable gap in research regarding the impact of UGI involvement on the intricate landscape of ensuing complications. This study aims to address this gap. Conducting a retrospective study at Chang Gung Memorial Hospital from January 2001 to September 2023, we compared CD patients with UGI (Montreal L4) involvement against non-L4 counterparts, focusing on baseline characteristics, post-diagnosis complications, and overall outcomes. Routine UGI endoscopy was performed around the time of diagnosis in all patients followed in our inflammatory bowel disease (IBD) center, and all CD patients with adequate follow-up were included in this study. The study included 212 CD patients, 111 in the L4 group and 101 in the non-L4 group, with an average follow-up of 40.8 ± 15.1months. At baseline, individuals in the L4 category demonstrated elevated smoking rates, increased Crohn's Disease Activity Index scores, a higher prevalence of strictures, and a more prevalent usage of biologics and proton pump inhibitors. Moreover, this group was characterized by reduced albumin levels. Upon concluding the follow-up, those with L4 involvement continued to show escalated CDAI scores and hospitalization frequencies, alongside heightened C-reactive protein levels and diminished albumin concentrations. Additionally, the occurrence of UGI involvement, stricturing disease at the time of diagnosis, and a younger age at the onset of CD were pinpointed as independent predictors for the development of new-onset strictures. CD patients with UGI involvement exhibit elevated disease activity and serve as independent predictors for the development of intestinal strictures. Thorough UGI evaluations at the time of diagnosis, coupled with assertive treatment strategies, are essential for managing these patients effectively.

#1852 When ‘pebbles’ affect the kidney: nephrolithiasis and chronic renal failure in Crohn's disease. The experience of a 3rd level centre

Abstract Background and Aims Nephrolithiasis is the most common expression of kidney involvement in chronic inflammatory bowel disease (IBD), especially in Crohn's disease (CD). Stone formation favoring factors are hyperoxaluria, dehydration, acidosis, common conditions in CD patient, who present a little higher incidence of renal stones, made of calcium oxalate, than the normal population. Only few studies focused on the relationship between CD activity (defined by CDAI score) and the development of nephrolithiasis and possible subsequent development of chronic renal failure (CRF). Materials and Method We conducted a retrospective study on a cohort of 1236 patients affected by CD referring to our Centre of IBD- Sant'Orsola between 2014 and 2021. We identified two cohorts from this population: 118 patients with nephrolithiasis and 118 patients without nephrolithiasis. Among these two groups, we identified variable clinical manifestations of CD and their relation with CRF and lithiasis. Results The prevalence of nephrolithiasis in all CD patients was 10.3%, a little higher than in the general population. The results of the analysis of patient and disease variables in the two groups are shown in Table 1. The mean age at diagnosis of CD was higher in the group without nephrolithiasis, so the treatment was started later. The presence of perianal disease, extraintestinal manifestations (MEI), like ankylosing spondylitis (APS), biliary tract involvement, or previous surgery, and presence of ileostomy correlate with the formation of stones in univariate regression analysis (Table 2). Perianal disease and MEI also maintained significance in multivariate analysis. Conclusion Our data suggest that a higher degree of disease activity, defined by the presence of perianal disease (a variable on CDAI score) and the presence of MEI, correlates with higher risk of lithiasis. It is advisable to start early the study of nephrolithiasis in these patients to adopt preventive strategies against formation and progression of renal stones. Future studies are required for a better definition of this deep relationship.

E058 Disease activity measurement in rheumatoid arthritis - simpler in not always better!

Abstract Background/Aims Rheumatoid arthritis is one of the commonest inflammatory arthritis (1). The traditional method of disease activity assessment would incorporate activity measures like DAS 28, CDAI and SDAI which have been validated in clinical research (2). All these indices use 28 joint assessment method. These measures use different aspects of disease activity including swollen joint count, tender joint count, patient global scores and physician global assessment scores and inflammatory markers are included in some of the measures. We conducted a small study to compare these outcome measures in patients with moderate RA (per DAS criteria) who were recruited for disease activity assessment through MSK ultrasound. Methods Of the 30 biologic naive patients recruited, 27 were included in this study. Patients with moderate disease activity (per DAS criteria) were recruited for MSK ultrasound evaluation by a single rheumatologist. Patients with a diagnosis of fibromyalgia were excluded. These patients had been reviewed by two assessors prior to USS assessment and disease activity measures updated. Patient data was collected through electronic patient records. Data was analysed through MS Excel. Results The median age was 63. There were 66% females and 34% male patients. Majority were sero positive for either RhF, Anti CCP or both (77%). Mean DAS-28 score was 4.4 and corresponding mean CDAI and SDAI scores were 22.8 and 23.5 respectively. Mean HAQ score 1.08 and median CRP was 8.6. The median composite EULAR OMERACT synovitis score was 9.18. The average physician global assessment score for disease activity before USS was 4.9/10 and it correlated well with decision to escalate treatment in 41% patients as a result of USS assessment. Conclusion With a small sample size, this project shows that simplified disease activity measures do not necessarily provide clear evidence of disease activity and are heavily influenced by patient reported outcome measures (tender joint count and global pain scores). CDAI scores can be slightly higher compared to DAS and SDAI scores for the similar patients. Physician assessment and ultrasound can provide robust evaluation of disease activity and help in decision-making. A multicentric study with a large simple size to evaluate these findings would be helpful. Judicious use of clinical evaluation and imaging can help in tailoring treatment according to patient’s clinical condition and can also save money. Disclosure H. Crawshaw: None. E. Gates: None. C. Acebes: None. M. Jamal: None.

Absolute monocyte counts could predict disease activity and secondary loss of response of patients with Crohn's disease treated with anti-TNF-α drug.

Assessing Crohn's disease (CD) activity is critical for monitoring disease progression. In CD, monocytes could release TNF-α. Thus, it is extremely important to study its role in the disease activity and loss of response to anti-TNF-α biologics. In this study, we collected CD patients treated with biologics from January 2017 to May 2022. Indicators associated with disease activity were evaluated by Spearman correlation analysis and Mann-Whitney U test. Specifically, logistic analyses were used to explore the predictors of primary nonresponse (PNR) and secondary loss of response (SLOR) within 1 year of anti-TNF-α agents. In addition, a nomogram was developed for therapeutic effect prediction. 283 patients with CD were identified. Disease activity group, defined as CDAI equal to or greater than 150, had significant elevated absolute monocyte counts than disease remission group based on CDAI score (p = 0.019, Z = -2.354). Logistic analyses showed that absolute monocyte counts could be an independent predictor of 1-year SLOR of anti-TNF-α agents in CD patients (p = 0.013). A nomogram established based on gender, absolute monocyte counts, and hemoglobin could predict SLOR within 1 year of anti-TNF-α agents reliably. The results of this study support the utility of absolute monocyte counts detecting disease activity and anti-TNF-α therapy effect in patients with CD.

Central sensitivity syndrome affects the disease activity index and treatment satisfaction in patients with rheumatoid arthritis.

Many rheumatoid arthritis (RA) patients prioritize pain improvement in treatment. As pain can result from various causes, including noninflammatory factors such as central sensitivity syndrome (CSS), we hypothesized that CSS might impact treatment satisfaction. In this cross-sectional study, we assessed the CSS effects on clinical disease activity and treatment satisfaction in RA patients. In total, 220 consecutive RA patients receiving long-term follow-up were evaluated for clinical disease activity and treatment satisfaction. CSS was evaluated using the Central Sensitization Inventory (CSI). An overall score of ≥40 indicates the presence of CSS. We queried "How satisfied are you with your treatment?"; answers included (a) very satisfied, (b) satisfied, (c) not satisfied, or (d) very dissatisfied. For univariate analysis, we condensed these answers into "dissatisfied" or "satisfied." We also evaluated treatment satisfaction using the visual analog scale (VAS), with scores ranging from 0 mm (very dissatisfied) to 100 mm (very satisfied). Of the 220 patients, 17 (7.7%) were classified as having CSS. CSI score was significantly correlated with the clinical disease activity index (CDAI; r = .322, p < .01) and treatment satisfaction (r = -.336, p < .01). Regarding treatment satisfaction, univariate analysis revealed that patient global assessment (PtGA), pain VAS, Health Assessment Questionnaire-Disability Index (HAQ-DI), Disease Activity Score in 28 joints with C-reactive protein, CDAI, and CSI scores of patients who were satisfied with treatment differed significantly from those of dissatisfied patients. Multivariate analysis revealed that CSI, PtGA, and HAQ-DI scores were associated with treatment satisfaction. In RA patients, CSS may affect the disease activity index and reduce treatment satisfaction.

Burden of Mental Health among Patients with Inflammatory Bowel Disease-A Cross-Sectional Study from a Tertiary IBD Center in Hungary.

Background: Inflammatory bowel diseases (IBDs) are chronic conditions that negatively affect the patient's quality of life. With the spread of the biopsychosocial model, the role of mental health in the activity and course of inflammatory bowel disease is becoming more and more recognized. Our study aimed to assess the prevalence of anxiety and depression in IBD patients in our tertiary referral center and determine the predictive factors of these mental conditions. Methods: A total of 117 patients were included consecutively between 1 December 2021 and 28 February 2022. We used a questionnaire to gather demographic information, disease course, and IBD-specific symptoms. We assessed anxiety symptoms using the GAD-7 and depressive complaints using the PHQ-9 questionnaire. We evaluated disease activity using CDAI and pMayo scores. Results: Of the 117 patients (male/female: 63/54), 88 suffered from Crohn's disease, and 29 were diagnosed with ulcerative colitis. Only 6 patients were taking medication for mood disorders, and 38 individuals sought mental support during their lifetime. A total of 15% of the population suffered from moderate-severe anxiety disorder, and 22% were affected by moderate-severe depression. The GAD-7 and PHQ9 values showed a significant correlation between the number of stools, bloody stools, abdominal pain, number of flare-ups, and CDAI scores. Conclusions: Our study confirmed that there is a high incidence of anxiety and depressive symptoms among IBD patients. Our results highlighted the symptoms that could be associated with mental disorders. It is important to assess the mental status of IBD patients to improve their quality of life.

Real-Life Comparison of Four JAK Inhibitors in Rheumatoid Arthritis (ELECTRA-i Study).

Background: Real-world evidence of the efficacy and adverse events of JAK inhibitor treatment (Tofacitinib, Baricitinib, Upadacitinib, and Filgotinib) in rheumatoid arthritis is still limited. Methods: We studied 115 patients from the Rheumatology Unit of S. Giovanni di Dio Hospital affected by D2T-RA, according to the 2010 EULAR criteria. Out of the 115 patients, 17 had been treated with Baricitinib 8 mg/daily, 32 with Filgotinib 200 mg/daily, 21 with Tofacitinib 10 mg/daily, and 45 with Upadacitinib 15 mg/daily. We evaluated the clinical response after 3, 6, and 12 months of treatment and the follow-up from September 2022 to September 2023. All patients were evaluated according to the number of tender joints (NTJs), number of swollen joints (NSJs), visual analog scale (VAS), global assessment (GA), health assessment questionnaire (HAQ), Disease Activity Score (DAS28), and CDAI. Furthermore, laboratory parameters of efficacy and tolerability were evaluated. Results: All treatments demonstrated a statistically significant decrease in the DAS28 and CDAI scores, tender and swollen joint counts, VAS, HAQ, and patient global assessment (PGA) after 3, 6, and 12 months of treatment. All treatments showed similar behavior, and statistically significant decreases in circulating calprotectin, TNFα, and IL-6 were observed for all drugs after 12 months of treatment. In addition, soluble urokinase plasminogen activator receptor (suPAR) values showed significant differences at baseline and after 12 months of treatment for Filgotinib: 4.87 ± 4.53 vs. 3.61 ± 0.9 (0.009) and Upadacitinib: 6.64 ± 7.12 vs. 4.06 ± 3.61 (0.0003), while no statistically significant differences were found for Baricitinib: 3.4 ± 0.1 vs. 3.78 ± 0.1 and Tofacitinib: 3.95 ± 1.77 vs. 2.58 ± 0.1. The TC/HDL-C ratio (atherogenic index) showed significant differences when comparing Baricitinib vs. Filgotinib (0.0012), Filgotinib vs. Tofacitinib (0.0095), and Filgotinib vs. Upadacitinib (0.0001); furthermore, the LDL-C/HDL-C ratio in the Filgotinib group did not change (2.37 ± 0.45 vs. 2.35 ± 2.13 (NS)) after 12 months of treatment. Venous Thrombotic Events (VTEs) and major adverse cardiovascular events (MACEs) accounted for 1% of adverse events after treatment with Baricitinib. Herpes zoster reactivation accounted for 1% of adverse events after treatment with Filgotinib and Tofacitinib, while non-melanoma skin cancer (NMSC) accounted for 1% of adverse events after Upadacitinib treatment. Conclusions: Our real-world data from patients with RA show differences in some laboratory parameters and in the impact of lipid metabolism in JAK inhibitor treatment.

SUBCUTANEOUS INFLIXIMAB (CT-P13 SC) DOSE ESCALATION AS AN OPTION FOR MANAGING THE LOSS OF RESPONSE IN INFLAMMATORY BOWEL DISEASE POST HOC ANALYSIS OF LIBERTY-UC AND LIBERTY-CD STUDY

Abstract INTRODUCTION Dose escalation of IV infliximab is an option for inflammatory bowel disease (IBD) patients who lose response after induction therapy. However, as yet, there is limited data for CT-P13 subcutaneous (SC) infliximab (CT-P13 SC) dose escalation in IBD patients. AIMS &amp; METHODS The aim of the post hoc analysis was to evaluate the efficacy, safety, and immunogenicity of treatment with CT-P13 SC dose escalation in patients who initially responded but then lost response according to the loss of response (LOR) criteria in LIBERTY-UC and LIBERTY-CD studies, which were conducted in parallel over 54 weeks. Patients with moderately to severely active UC and CD were treated with 3 doses of infliximab IV 5mg/kg as induction therapy. Clinical responders at Week 10 were randomized (2:1) to receive either CT-P13 SC 120 mg or placebo every 2 weeks as maintenance therapy. From Week 22, the patients who received CT-P13 SC 120 mg every 2 weeks and who met LOR criteria were permitted to escalate the dose to CT-P13 SC 240 mg (double injection [2 shots] of CT-P13 SC 120 mg) every 2 weeks. RESULTS A total of 294 and 231 patients were randomized to CT-P13 SC 120mg in UC and CD study, each. Among them, dose escalation from CT-P13 SC 120 mg to CT-P13 SC 240 mg prior to Week 54was more common in UC than CD [27.6% (81/294) vs 16.9% (39/231)]. Of dose-escalated patients, 74.1% (60/81) and 51.3% (20/39) received their first dose of CT-P13 SC 240 mg at Week 22 in the UC and CD studies, respectively. In both UC and CD studies, patients showed improvement in terms of clinical remission [In UC, 24.7% (20/81), In CD, 53.8% (21/39)] or endoscopic response [In CD, 28.2% (11/39)] after dose escalation. Compared to the first dose escalation visits, patients who escalated the dose had almost a half, statistically significant, reduction in modified Mayo score in UC and CDAI score in CD at Week 54. (Table 1). The incidence rate of treatment-emergent adverse events (TEAEs) in the maintenance period of both studies was comparable between patients with and without dose escalation. [In UC, 72.8% (67/92) vs 65.2% (133/204), In CD, 71.1% (32/45) vs 72.5% (140/193)]. Among these, TEAEs of infection were as follows [In UC, 27.2% (25/92) vs 28.4% (58/204), In CD, 35.6% (16/45) vs 30.1% (58/193)]. In both studies, rates of anti-drug antibody (ADA) positive conversion up to Week 54 showed no difference in patients with and without dose escalation as follows [In UC, ADA 55.7% (49/88) and 67.3% (134/199), respectively. In CD, ADA 68.2% (30/44) and 64.4% (121/188), respectively]. CONCLUSION Dose escalation of CT-P13 SC from 120 mg to 240 mg every 2 weeks may be effective in restoring efficacy. Safety profiles including immunogenicity results were generally comparable between patients with or without dose escalation. No new safety concerns were found after dose escalation.

COMPARATIVE EFFICACY AND SAFETY OF SUBCUTANEOUS INFLIXIMAB AND VEDOLIZUMAB MAINTENANCE THERAPY IN PATIENTS WITH CROHN’S DISEASE AND ULCERATIVE COLITIS: AN INDIRECT COMPARISON FROM RANDOMIZED CONTROLLED TRIALS

Abstract BACKGROUND In a previous meta-analysis on randomized controlled trials (RCT) in patients with moderate-to-severe Crohn’s disease (CD) and ulcerative colitis (UC), infliximab (IFX) showed better efficacy in the induction phase and comparable efficacy during the maintenance phase and an overall similar safety profile as compared to vedolizumab (VDZ).1 The objective of this study is to indirectly compare the 1-year efficacy and safety results between subcutaneous IFX (SC IFX) and VDZ as maintenance therapies in moderate-to-severe CD and UC patients. This analysis incorporates data from three recently published clinical trials: LIBERTY-CD2, LIBERTY-UC3, and VISIBLE24. METHODS Separate pooled analyses were conducted for patients with CD and UC, combining data for predefined efficacy and safety outcomes. These outcomes included the proportions of patients achieving clinical remission (CD: absolute CDAI score of &amp;lt;150; UC: Total Mayo score ≤2 with no individual sub-score &amp;gt;1; or partial Mayo score of ≤1 point), clinical responses (CD: decrease in CDAI score of ≥100 from baseline; UC: a decrease in total Mayo score from baseline of ≥3 points and ≥30%; or a decrease in partial Mayo score from baseline of ≥2 points), and the proportions of patients experiencing adverse events (AEs), serious AEs, serious infections, or discontinuation due to AEs during the 1-year maintenance phase. Data were pooled using a random-effect model. The heterogeneity between studies was examined. RESULTS A total of 2,028 patients (IFX SC, n=655; VDZ, n=1,373) were included in this pooled analysis. In CD patients, a higher proportion of patients treated with SC IFX achieved clinical remission and CDAI-100 response, with non-overlapping 95% CI during the maintenance phase compared to patients treated with VDZ (Fig.1A, B). In UC, the proportion of patients achieving clinical remission and clinical response during the maintenance phase was similar between the two treatment groups, with overlapping 95% CIs (Fig.1C, D). Safety profiles were generally similar for both indications (Fig.2). CONCLUSION In this indirect comparison, patients treated with SC IFX achieved better efficacy in terms of clinical remission and response compared to those treated with VDZ during 1-year maintenance therapy in CD, and similar rates in UC. Subcutaneous IFX showed a similar safety profile to VDZ, with limitations in duration of follow-up and number of patients. These findings align with the results of a network meta-analysis5 showing that SC IFX ranks highest among biologics for achieving clinical remission during maintenance therapy. REFERENCES 1. Peyrin-Biroulet et al., BMC Gastroenterol 2022;22(1):291 2. Colombel J F et al., JCC 2023;17(S1):i161-i162 3. Sands B E et al., JCC 2023;17(S1):i623-i624 4. Severine Vermeire et al., JCC 2022;16(1):27-38 5. Peyrin-Biroulet L et al., JCC 2023:17(S1):i574–i576

P681 Preliminary data from the Biologic and Partial Enteral Nutrition in Crohn’s Disease Study (BIOPIC)

Abstract Background Biologics such as adalimumab (ADA) are used to induce clinical remission (CR) in individuals with active Crohn’s disease (CD) but around 50% of patients actually achieve clinical remission. Exclusive enteral nutrition is also an effective induction treatment, but tolerability limits its use, especially in adults. This study aimed to assess the efficacy and tolerability of partial enteral nutrition (PEN) in combination with ADA compared to ADA monotherapy. Methods In this multi-centre (n=8) RCT (NCT04859088), adults with active CD (Crohn’s Disease Activity Index, CDAI ≥ 150) due to start ADA as their first-line biologic were randomised to either continue their habitual unrestricted diet (UD) or to replace half of it with PEN during their first 6 weeks of induction treatment Primary outcome clinical efficacy (i.e., clinical response, CDAI baseline decrease of ≥ 70 or CR, CDAI score &amp;lt;150) was assessed after 12 weeks of ADA initiation. Secondary outcomes included changes in inflammatory markers (faecal calprotectin, (FCAL), CRP) and quality of life (SIBDQ), at 3 (only FCAL), 6 and 12 weeks. To calculate adherence to PEN, used/unused tins were returned and compared to number provided. Analysis was performed using intention-to-treat analysis. Results 32 participants (13 UD, 19 PEN) have completed the study; 29 (13 UD, 16 PEN) of whom completed the full 12 weeks of the study. Adherence rate to PEN was high (~96%). Clinical efficacy (response &amp; remission) was UD: 92% vs PEN: 84%, p=0.490 at 6 weeks and UD: 85% vs PEN: 58%, p=0.11 at week 12. FCAL data was available for 22 participants (9 UD, 13 PEN). FCAL (g/g) significantly decreased after 12 weeks in patients receiving PEN (mean difference 189, p=0.009) but this effect did not quite reach statistical significance (p=0.052) in the UD group (Fig 1). Proportionally more patients from the PEN group had FCAL &amp;lt;100 mg/kg compared to the UD group (3, 6, 12 weeks, PEN: 62%, 69%, 69% vs UD: 33%, 33%, 56%) during the study course. CRP (mg/L) significantly decreased at week 6 and 12 in patients receiving PEN (week 6 &amp; week 12, p&amp;lt;0.0001) and in patients continuing their UD (week 6, p=0.001, week 12, p=0.007). SIBDQ score increased in both groups (PEN, p=0.023 vs UD, p=0.008). Conclusion Preliminary data from the BIOPIC study suggests equivalence in clinical efficacy between the two groups but better responses to blood and gut inflammatory markers when ADA is combined with PEN. High tolerability of PEN suggests it can be a viable option for adult patients with active luminal CD.

P873 Ustekinumab Real World Evidence Study (UndieS): Assessing the suitability of patients treated in routine clinical care for participation in the pivotal phase 3 clinical trial

Abstract Background Phase 3 randomised controlled trials (RCTs) are recognised as the gold standard for measuring the efficacy of new medicines and are essential for licensing new products. To maximise internal validity, RCTs recruit a highly selected, carefully defined group of participants, whereas patients treated in routine practice are much more heterogeneous. We set out to describe the real-world use of ustekinumab and assess the proportion of treated patients who would have been eligible for the relevant registration studies. Methods UndieS is a UK-based, multicentre, prospective, observational study investigating the effectiveness of ustekinumab in 593 Crohn’s disease patients. Objective evidence of active Crohn’s disease (biochemical or endoscopic) and/or failure or intolerance to another therapy were the only entry criteria. Within the limits of the study, we compared participants’ characteristics with the eligibility requirements of the UNITI clinical trial programme. The pragmatic modified Harvey-Bradshaw Index (mHBI), shown to correlate to CDAI score, was used in UndieS. No endoscopic follow up information was collected. Results 82% of patients treated in this real-world study would not have been eligible for participation in the UNITI programme. Eight RCT eligibility criteria would each be expected to exclude at least 10% of the real-world patient population (figure 1). A low disease activity score was the eligibility criterion most frequently expected to render UndieS participants ineligible for the UNITI programme with 61% of predicted CDAI scores (i.e. estimated from mHBI) falling below the threshold for RCT eligibility, despite 80% of those treated having objective evidence of inflammation and 55% failed/ were intolerant to an alternative therapy. Only 13% of participants were using corticosteroids at baseline. 59% of UndieS participants had previously failed or been intolerant to at least one anti-TNFα medication. For those who would have been ineligible for the RCT based on laboratory tests, an elevated ALT was the commonest abnormality among UndieS participants. The requirements for multiple venepunctures and pregnancy avoidance were the most relevant impediments for UndieS patients, with 28% of females of childbearing potential not willing to agree to the specified conditions. Conclusion Within the limitations of this study, we have demonstrated a significant disparity between participants in phase 3 RCTs and patients treated in routine clinical care. This questions the applicability of efficacy studies to real world clinical practice. Data from high quality, observational studies should complement findings from RCTs to support decision makers. Future work will investigate whether outcomes differ according to RCT eligibility.

P960 Comparison of clinical outcomes by induction therapy response status in patients with Inflammatory Bowel Disease (IBD) treated with subcutaneous (SC) versus intravenous (IV) infliximab (IFX): Post hoc analysis of a pivotal, randomised controlled trial

Abstract Background Clinical associations between initial response and long-term outcome are well established for IV IFX in IBD.1,2 In 2020, SC IFX was approved in Europe for treating moderate-to-severe Crohn’s disease (CD) or ulcerative colitis (UC), based on a pivotal randomised trial (NCT02883452) comparing SC and IV IFX.3 This post hoc analysis investigated clinical outcomes in patients (pts) treated with SC or IV IFX, by response to IV IFX induction. Methods In the pivotal trial, adults with active CD or UC received IV IFX induction (5 mg/kg; Week [W] 0 and W2), before randomisation to SC (n=66) or IV (n=65) arms. W6 clinical response (≥70-point decrease in Crohn’s Disease Activity Index [CDAI] score [CD]; ≥2-point decrease in partial Mayo score with ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1 [UC]) was a stratification factor. The SC arm received SC IFX (120/240 mg for pts weighing &amp;lt;80/≥80 kg) every 2 weeks from W6–54; the IV arm received IV IFX 5 mg/kg every 8 weeks (W6–22), then switched to SC IFX (W30–54). Rates of clinical remission (CDAI score &amp;lt;150 [CD]; partial Mayo score ≤1 [UC]) and trough IFX concentrations (Ctrough) were assessed at W6, W30 and W54. Analyses were descriptive. Results There were 101 induction responders (IRs) to IV IFX, who were randomised to the SC arm (n=49, 74.2%; SC-IR subset) or the IV arm (n=52, 80.0%; IV-IR subset). Correspondingly, there were 17 (25.8%) and 13 (20.0%) induction non-responders (INRs; SC-INR and IV-INR subsets, respectively). In both study arms, IRs had higher clinical remission rates than INRs at both W30 and W54 (Figure A). Comparing by formulation, the SC-INR subset had nearly twice the W30 clinical remission rate of the IV-INR subset (58.8% vs. 30.8%; p=0.159 [Fisher exact test]). In addition, IV-INR subset clinical remission rates numerically increased after pts switched to SC IFX (W30: 30.8% vs. W54: 46.2%; p=0.476 [McNemar test]). These observations were generally consistent with Ctrough findings (Figure B); median Ctrough in the IV-INR subset increased from 1.5 to 18.3 µg/mL (p=0.005 [Wilcoxon signe-drank test]) after switching to SC IFX. Conclusion Findings suggested associations between initial response to IFX induction therapy and positive long-term outcomes for both SC and IV IFX, and supported potential benefits with SC IFX maintenance therapy for INRs, compared with the option of IV IFX maintenance. Given the post hoc nature of the analysis and the small analysis population (thus statistical inconclusiveness), investigation in larger studies is warranted. 1Murthy SK et al. Inflamm Bowel Dis 2015;21:2090–6. 2Wong ECL et al. J Crohns Colitis 2021;15:1114–9. 3Schreiber S et al. Gastroenterology 2021;160:2340–53.

P1087 A retrospective study on the GLIM criteria for assessing malnutrition in patients with Crohn's Disease and its correlation with clinical outcomes

Abstract Background It is a common occurrence for patients with Crohn's disease (CD) to suffer from malnutrition. A novel approach to assessing malnutrition has been devised by the Global Leadership Initiative on Malnutrition (GLIM). Therefore, the objective of this study was to investigate the prevalence of malnutrition in CD patients using GLIM criteria and evaluate the clinical utility of GLIM in this population. Methods A retrospective cohort study was conducted with 386 patients with Crohn's disease. Data were extracted from the medical records, including demographic and clinical characteristics. All patients were evaluated using the nutritional screening and diagnosis criteria of the NRS 2002 and the GLM criteria. The prevalence of malnutrition was reported and the relationship between malnutrition and clinical outcome was analyzed. Results The prevalence of malnutrition among CD patients was 73.6% and 35.1% in mild malnutrition, 35.4% in moderate malnutrition, and 35.4% in severe malnutrition. The majority (143, 50.4%) of malnourished patients were categorized as B2 or B3 phenotype, with a significant difference (P= 0.001). The malnourished group had significantly higher CDAI scores than the non-malnourished group (122.9±70.5 vs. 77.3±61.3, P&amp;lt;0.001). In the primary cohort, patients at risk of malnutrition with inflammatory load exhibited a significantly worse clinical outcome compared to those without inflammatory load (OR 4.07, 1.56-10.7; P=0.004). Conclusion Malnutrition caused by Crohn's disease is a significant issue for numerous patients. Malnutrition identified using the GLIM criteria was found to be associated with CDAI, age, and behavior, providing prognostic value for clinical outcomes.

Azathioprine Plus Exclusive Enteral Nutrition Versus Azathioprine Monotherapy for the Prevention of Postoperative Recurrence in Patients with Crohn's Disease: An Open-Label, Single-Centre, Randomized Controlled Trial.

Azathioprine [AZA] effectively prevents postoperative endoscopic recurrence [ER] in Crohn's disease [CD]. However, the efficacy of AZA emerges after 3 months. Exclusive enteral nutrition [EEN] can maintain remission in CD. The present trial investigates whether AZA plus postoperative 3-month EEN is superior to AZA alone in preventing ER of CD. In total, 84 high-risk CD patients undergoing intestinal resection received AZA alone or AZA plus 3 months of EEN [AZA + EEN] postoperatively. The primary endpoint was the rate of ER at 12 months. Secondary endpoints included the rate of ER at 3 months, clinical recurrence [CR], CD activity index [CDAI] scores, faecal calprotectin [FC], and C-reactive protein [CRP]. Quality of life was assessed using Short Form-36 [SF-36] and the Inflammatory Bowel Disease Questionnaire [IBDQ]. Patients in the AZA + EEN group exhibited significantly lower rates of ER compared to the AZA group at both 12 months (33.3% [13/39] vs 63.2% [24/38], P = 0.009) and 3 months (8.6% [3/35] vs 28.1% [9/32], P = 0.037) post-surgery. The rates of CR between the two groups at 3 and 12 months were similar. CDAI scores, FC, albumin level, and CRP were all comparable between the two groups. Quality of life was significantly higher in the AZA group than in the AZA + EEN group at 3 months but became comparable from 5 to 12 months postoperatively. In high-risk CD patients, combining AZA with postoperative 3-month EEN reduces 1-year ER but may temporarily impact quality of life. Further large-scale, long-term studies are warranted. NCT05214430.

Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive

BackgroundThe HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive.MethodsAbatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used.ResultsIn the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045).ConclusionIn this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort..

Prospective study of an adalimumab combined with partial enteral nutrition in the induction period of Crohn’s disease

BackgroundAdalimumab monotherapy can suppress gut inflammation and induce remission in active Crohn’s disease but has some limitations. Exclusive enteral nutrition (EEN) is recommended for patients with mild to moderate Crohn’s disease (CD), but implementation is challenging.AimTo evaluate the effectiveness of adalimumab combined with partial enteral nutrition (PEN) in the induction therapy for Crohn’s disease.MethodsA prospective cohort study was designed and a total of 56 patients with active CD who met the criteria for enteral nutrition (EN) treatment in our hospital were selected. The baseline data of all patients were collected including age, sex and other general information. The changes in fecal calprotectin, C-reactive protein (CRP), albumin(Alb), hemoglobin (Hb), platelets (Plt), erythrocyte sedimentation rate (ESR), Crohn’s disease activity index score (CDAI), simple endoscopic score (SES-CD) and body mass index (BMI) were compared between the adalimumab combined with enteral nutrition (ADA+EN) group (N = 37) the adalimumab group (ADA) (N = 19) at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated. Then the ADA+EN group was divided into an adalimumab combined with exclusive enteral nutrition subgroup (ADA+EEN) and an adalimumab combined with partial nutrition subgroup (ADA+PEN) according to enteral nutrition intake. The changes in fecal calprotectin, CRP, Alb, Hb, Plt, ESR and CDAI, SES-CD and BMI were compared between the ADA+EEN group and the ADA+PEN group at week 0 (W0) and treatment outcomes at week 12(W12). The differences between the two groups before and after treatment were evaluated. To evaluate the effectiveness of the two treatments on patients’ quality of life, nutritional recovery and body composition, patients in the ADA+EN group were needed to complete the Inflammatory Bowel Disease Questionnaire (IBDQ), EQ-5D-5L, the EuroQol visual analogue scale (EQ-VAS) and body composition analysis.A total of 28 patients completed all questionnaires and body composition analyses at week 0 and week 12, including 10 patients in the ADA+EEN group and 18 patients in the ADA+PEN group, respectively. The differences of in IBDQ, EQ-5D-5L and body composition analysis were compared between the two groups at week 0 (W0) and treatment outcomes at week 12(W12). Additionally, the differences between the two groups before and after treatment were evaluated.ResultsThese investigated indexes such as calprotectin, Hb, Plt, ESR, Alb, BMI, CRP, CDAI and SES-CD scores were significantly different before and after treatment in the ADA+EN group (p < 0.01). However, fecal calprotectin, Hb, SES-CD scores and Alb in the ADA group were not statistically significantly different from W0 to W12 (p > 0.05). The fecal calprotectin and CDAI scores in the ADA+EN group were significantly lower than those in the ADA group after treatment. The differences in all factors before and after treatment between the ADA+PEN group and the ADA+EEN group were statistically significant (p < 0.05). However, there was no significant difference between the two groups at week 12 (p > 0.05).ConclusionAdalimumab combined with EN are more effective than ADA monotherapy in terms of endoscopy and clinical remission. By comparing the investigated indicators such as calprotectin, Hb, Plt, ESR ,CRP and SES-CD scores, it was proven that adalimumab combined with partial enteral nutrition or exclusive enteral nutrition has the same remission effect in induced Crohn’s disease. The combination of biological agents and partial nutrition can improve medical order compliance, psychological burden and quality of life. Therefore, adalimumab combined with partial nutrition can be used as the first-line treatment for CD induced remission.

Оценка эффективности тофацитиниба, упадацитиниба и олокизумаба у больных ревматоидным артритом в реальной клинической практике

Aim: to perform an indirect comparative analysis of changes over time in clinical and laboratory parameters of inflammatory activity of rheumatoid arthritis (RA) in patients who receive tofacitinib (TOFA), upadacitinib (UPA), and olokizumab (OKZ) in real clinical practice. Patients and Methods: the study included 30 patients with advanced RA and moderate or high activity (DAS28-ESR score) who had ineffective prior therapy with methotrexate, leflunomide, or genetically engineered biological drugs for at least 6 months. The patients were divided into three groups: 10 patients received TOFA 5 mg twice daily, 10 patients received UPA 15 mg daily, and 10 patients received OCZ 64 mg subcutaneously every 4 weeks. The patients underwent examination before treatment, as well as after 3 and 6 months. The serum level of interleukin 6 (IL-6) was measured using multiplex xMAP technology on the Bio-PlexTM 200 System analyzer (BIO-RAD, USA). Results: treatment with TOFA, UPA, and OCZ was associated with a decrease in DAS28-ESR, CDAI, SDAI, and HAQ-DI scores after 3 months. After 6 months, UPA was found to be superior to TOFA in terms of reducing CDAI and SDAI. Treatment with TOFA resulted in a decrease in IL-6 levels after 3 and 6 months. The study found that UPA did not have an effect on IL-6 levels. However, therapy with OCZ resulted in an increase in IL-6 levels after 3 months, followed by a decrease after 6 months. Despite this, IL-6 levels did not return to baseline values. Conclusion: the results of the study suggest that there are differences in the clinical effects of Janus kinase (JAK) inhibitors and OCZ in RA patients. Nevertheless, all drugs were found to be effective in suppressing RA activity, regardless of baseline IL-6 levels and changes during treatment. KEYWORDS: rheumatoid arthritis, interleukin 6, tofacitinib, upadacitinib, olokizumab, disease activity, therapy efficacy. FOR CITATION: Lapkina N.A., Baranov A.A., Leont'eva E.A., Amirdzhanova V.N., Kolin'ko A.A., Ashikhmin G.M. Efficacy of tofacitinib, upadacitinib and olokizumab in rheumatoid arthritis in real clinical practice. Russian Medical Inquiry. 2024;8(2):51–59 (in Russ.). DOI: 10.32364/2587-6821-2024-8-2-1.