Adalimumab Monotherapy Research Articles

DOP75 Frequency and effectiveness of dose escalation of biologic therapy in Inflammatory Bowel Disease: The RAINBOW-IBD study of ENEIDA

Abstract Background Despite their effectiveness in inflammatory bowel disease (IBD), biologic drugs often require dose escalation. Primary aim: To describe the frequency and effectiveness of dose escalation of biologics: infliximab (IFX), adalimumab (ADA), golimumab (GOL), vedolizumab (VED), and ustekinumab (UST). Secondary: To study the reasons for and the durability of escalation, and to identify predictive factors for relapse and for therapy discontinuation after it. Methods Adult patients from ENEIDA registry who received biologics were included. Dose escalations were specifically analysed. Survival curves assessing the impact of several variables on the durability and on clinical relapse were compared using the log-rank test. Predictive factors associated with therapy discontinuation and the risk of relapse after dose escalation were assessed by Cox-regression. Results Out of the 19,720 patients with biologics included in ENEIDA, 5,096 (26%) had their dose escalated, which were analysed. The frequency of escalation per patient-year of follow-up was: 5% (95% confidence interval [CI]=4.3-5.6%), 7% (6.3-7.7%), 7% (6.9-7.1%), 10% (9.9-10.1%), and 12% (11.9-12.1%) in patients receiving IFX, ADA, GOL, VED and UST, respectively (Figure 1). The main reason for dose escalation was loss of response (60%). Remission and clinical response were recaptured after dose escalation, respectively, in: 49% and 89% (IFX), 41% and 86% (ADA), 46% and 85% (GOL), 32% and 87% (VED), and 47% and 92% (UST). The probability of maintaining the dose escalated at 12 and 24 months was: 88% and 78% (IFX); 82% and 71% (ADA); 82% and 66% (GOL); 84% and 75% (VED); and 93% and 88% (UST), respectively (Figure 2). Predictive factors of relapse after re-achieving remission with dose escalation were: 1) IFX: previous biologic exposure (Hazard ratio [HR]=1.2, 95%CI=1.1-1.4), and IBD duration (HR=0.97, 95%CI=0.96-0.99); 2) ADA: ADA monotherapy (HR=1.2, 95%CI=1.01-1.35); 3) VED: Crohn’s disease (HR=1.56, 95%CI=1.1-2.2), and IBD duration (HR=0.9, 95%CI=0.8-0.99); and 4) UST: ulcerative colitis (HR=2.4, 95%CI=1.5-3.9). Predictive factors of therapy discontinuation after dose escalation were: 1) IFX: previous biologic exposure (HR=1.2, 95%CI=1.1-1.4), and disease duration (HR=0.98, 95%CI=0.97-0.99); 2) ADA: ADA monotherapy (HR=1.2, 95%CI=1.1-1.25); and 3) UST: ulcerative colitis (HR=1.4, 95%CI=1.1-1.9). Conclusion A proportion of IBD patients dose escalate biologics in the long-term. Dose escalation is an effective strategy to recapture response and remission. The durability of escalation seems to be relatively high over time. Prior biologic experience, IBD type, and a short evolution of IBD were identified as predictive factors of relapse and therapy discontinuation after dose escalation.

P518 Dietary and non-dietary predictors of treatment response to adalimumab in anti-TNFα-naïve adults with Crohn’s disease

Abstract Background Biologics, such as anti-TNFα agents, are commonly used in the management of Crohn’s disease (CD). A significant proportion of patients do not respond to treatment, necessitating the exploration of pre-treatment predictors of treatment response. Methods Anti-TNFα-naïve adults with active CD (Crohn’s Disease Activity Index; CDAI≥150) participating in an RCT (NCT04859088) were randomised to receive adalimumab monotherapy or adalimumab combination therapy with 50% partial enteral nutrition (PEN). Treatment response (CDAI<150) was assessed after 6 weeks, baseline diet was assessed with EPIC-Norfolk FFQ, alternative Mediterranean diet scores (aMED), and principal component analysis (PCA) with orthogonal (varimax) rotation was used to identify data-derived dietary patterns. Baseline predictors evaluated included PEN use, steroid use, immunomodulator use, age, disease duration, CDAI, C-Reactive protein (CRP), albumin, haemoglobin, Scottish Index of Multiple Deprivation (SIMD) score, adherence to dietary patterns identified, aMED score, smoking status, alcohol consumption, physical activity level, body mass index (BMI), fat mass (kg/m2), fat-free mass (kg/m2), and handgrip strength. Differential analysis between responders and non-responders was carried out with general linear model or chi-square test when appropriate. Random forest model with recursive feature elimination (RF-RFE) was used to identify the most predictive factors of treatment response. Results Of 42 participants recruited to the study, 62% (26) responded to treatment. PCA revealed four dietary patterns (Figure 1A). Responders to adalimumab were younger (mean (SD): 36.0 (17.1) vs 50.8 (10.0), P=0.004), had lower baseline CDAI (mean (SD): 228 (62) vs 286 (78), P=0.018), higher CRP (14.5 (19.2) vs 4.6 (5.8) mg/L, P=0.036), were less likely to smoke (31% (5 of 16) vs 8% (2 of 26), and less likely to adhere to a dietary pattern characterised by high consumption of animal products (PC2) (P=0.030). Adherence to PC2 also correlated positively with age (r=0.327, P=0.035). The RF-RFE algorithm highlighted young age, low baseline CDAI and low PC2 adherence as key factors (Sensitivity: 77%, Specificity: 63%, PPV: 77%, NPV: 63%, OOB: 29%, P=0.012) (Figure 1B). Interestingly, exclusion of dietary factors improved diagnostic performance of the model (Sensitivity: 77%, Specificity: 75%, PPV: 83%, NPV: 67%, OOB: 24%, P=0.003) (Figure 1C), indicating potential interactions by other factors like age. Conclusion Young age, non-smoking, low baseline CDAI and elevated CRP predict adalimumab response in anti-TNFα-naïve adults. While dietary factors may also play a role, their impact seems confounded by other non-dietary factors. Further research is warranted in this area.

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 <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 & 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 <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 & week 12, p<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.

Durability of Adalimumab and Infliximab in Children With Crohn's Disease: A Nationwide Comparison From the epi-IIRN Cohort.

In a nationwide cohort, we aimed to compare the durability of infliximab and adalimumab as first biologic treatment in children with Crohn's disease (CD), stratified as combotherapy or monotherapy. We used data from the epi-IIRN cohort that includes all patients with inflammatory bowel diseases in Israel. Durability was defined as consistent treatment without surgery or treatment escalation. All comparisons followed stringent propensity-score matching in Cox proportional hazard models. Of the 3487 children diagnosed with CD since 2005, 2157 (62%) received biologics (1127 [52%] infliximab, 964 [45%] adalimumab and 52 [2%] vedolizumab as first biologic), representing a higher proportion than that among adults diagnosed during the same time period (5295 of 15 776 [34%]; P < .001). Time from diagnosis to initiation of biologic was shorter in pediatric-onset compared with adult-onset disease (median time during the last 3 years was 2.7 months [interquartile range 1.2-5.4] vs 5.2 months [2.6-8.9]; P < .001). The durability of adalimumab monotherapy after 1 and 5 years from initiation of treatment was better than infliximab monotherapy (79%/54% vs 67%/37%, respectively; n = 452 matched children; hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.3-2.3; P < .001), while in those treated with combotherapy, durability was similar (94%/66% with infliximab vs 90%/54% with adalimumab; n = 100; HR, 1.7; 95% CI, 0.9-3.3; P = .1). Durability was higher in children treated with infliximab combotherapy vs infliximab monotherapy (87%/45% vs 75%/39%; n = 440; HR, 1.4; 95% CI, 1.1-1.8; P = .01). The durability of adalimumab monotherapy was similar to infliximab combotherapy (83%/53% vs 89%/56%, respectively; n = 238; HR, 0.9; 95% CI, 0.7-1.2; P = .4). Our results support using adalimumab monotherapy as a first-line biologic in children with CD. When infliximab is used, combotherapy may be advantageous over monotherapy.

Prospective study to characterize adalimumab exposure in pediatric patients with rheumatic diseases

BackgroundIn pediatric rheumatic diseases (PRD), adalimumab is dosed using fixed weight-based bands irrespective of methotrexate co-treatment, disease activity (DA) or other factors that might influence adalimumab pharmacokinetics (PK). In rheumatoid arthritis (RA) adalimumab exposure between 2–8 mg/L is associated with clinical response. PRD data on adalimumab is scarce. Therefore, this study aimed to analyze adalimumab PK and its variability in PRD treated with/without methotrexate.MethodsA two-center prospective study in PRD patients aged 2–18 years treated with adalimumab and methotrexate (GA-M) or adalimumab alone (GA) for ≥ 12 weeks was performed. Adalimumab concentrations were collected 1–9 (maximum concentration; Cmax), and 10–14 days (minimum concentration; Cmin) during ≥ 12 weeks following adalimumab start. Concentrations were analyzed with enzyme-linked immunosorbent assay (lower limit of quantification: 0.5 mg/L). Log-normalized Cmin were compared between GA-M and GA using a standard t-test.ResultsTwenty-eight patients (14 per group), diagnosed with juvenile idiopathic arthritis (71.4%), non-infectious uveitis (25%) or chronic recurrent multifocal osteomyelitis (3.6%) completed the study. GA-M included more females (71.4%; GA 35.7%, p = 0.13). At first study visit, children in GA-M had a slightly longer exposure to adalimumab (17.8 months [IQR 9.6, 21.6]) compared to GA (15.8 months [IQR 8.5, 30.8], p = 0.8). Adalimumab dosing was similar between both groups (median dose 40 mg every 14 days) and observed DA was low. Children in GA-M had a 27% higher median overall exposure compared to GA, although median Cmin adalimumab values were statistically not different (p = 0.3). Cmin values ≥ 8 mg/L (upper limit RA) were more frequently observed in GA-M versus GA (79% versus 64%). Overall, a wide range of Cmin values was observed in PRD (0.5 to 26 mg/L).ConclusionThis study revealed a high heterogeneity in adalimumab exposure in PRD. Adalimumab exposure tended to be higher with methotrexate co-treatment compared to adalimumab monotherapy although differences were not statistically significant. Most children showed adalimumab exposure exceeding those reported for RA with clinical response, particularly with methotrexate co-treatment. This highlights the need of further investigations to establish model-based personalized treatment strategies in PRD to avoid under- and overexposure.Trial registrationNCT04042792, registered 02.08.2019.

Subcorneal pustular dermatosis successfully treated with adalimumab monotherapy: A case report

Subcorneal pustular dermatosis successfully treated with adalimumab monotherapy: A case report

Improved clinical effectiveness of adalimumab when initiated with clindamycin and rifampicin in hidradenitis suppurativa.

Adalimumab monotherapy for hidradenitis suppurativa (HS) is often insufficient with a maximum clinical efficacy of 60% in Hidradenitis Suppurativa Clinical Response (HiSCR) and limited effect on draining tunnels. Data suggest that adalimumab therapy could be improved by concomitant antibiotics. To compare the clinical effectiveness of adalimumab with clindamycin and rifampicin versus adalimumab monotherapy after 12 weeks. This retrospective study included patients who started adalimumab with additional clindamycin and rifampicin and patients treated with adalimumab monotherapy, matched on sex and refined Hurley score. The primary outcome measure was the difference in change in the International Hidradenitis Suppurativa Severity Score System (IHS4) at 12 weeks. In total, 62 patients were included in the combination therapy group (n = 31) and adalimumab monotherapy group (n = 31), showing comparable IHS4 scores; 32.5 versus 29, p = 0.87 at baseline respectively. The combination therapy demonstrated greater clinical effectiveness expressed in median IHS4 improvement (-20 vs. -9, p < 0.001), IHS4-55 (74% vs. 36%, p = 0.002), median draining tunnel reduction (-4 vs. -2, p < 0.001) and pain response (47% vs. 27%, p = 0.02). Adalimumab initiated with clindamycin and rifampicin shows greater clinical effectiveness than adalimumab monotherapy. An important difference in effect was observed in the decrease of draining tunnels, addressing a serious limitation of adalimumab monotherapy.

Vedolizumab, Adalimumab, and Methotrexate Combination Therapy in Crohn’s Disease (EXPLORER)

Although biologics have revolutionized the treatment of Crohn's disease (CD), an efficacy ceiling has been reached. Combining biologic therapies may improve remission rates. EXPLORER, a phase 4, single-arm, open-label study, evaluated triple combination therapy with vedolizumab (300 mg on day 1, weeks 2 and 6, and then every 8 weeks), adalimumab (160 mg on day 2, 80 mg at week 2, then 40 mg every 2 weeks), and methotrexate (15 mg weekly) in biologic-naïve patients with newly diagnosed, moderate- to high-risk CD. Endoscopic remission at week 26 (primary end point; Simple Endoscopic Score for CD ≤2), clinical remission at weeks 10 and 26 (secondary end point; Crohn's Disease Activity Index <150), and incidences of adverse events and serious adverse events were evaluated. Among 55 enrolled patients, the mean CD duration was 0.4 years, the mean baseline Simple Endoscopic Score for CD was 12.6, and the mean baseline Crohn's Disease Activity Index was 265.5. At week 26, 19 patients (34.5%) were in endoscopic remission. At weeks 10 and 26, 34 (61.8%) and 30 patients (54.5%), respectively, were in clinical remission. Post hoc Bayesian analysis showed that the probabilities that triple combination therapy produced a higher endoscopic remission rate (33.5%; 95% credible interval, 22.4-45.7) than placebo (14%), vedolizumab monotherapy (27%), or adalimumab monotherapy (30%) were 99.9% or higher, 86.3%, and 71.4%, respectively. Six patients had serious adverse events. Combination therapy resulted in endoscopic and clinical remission at week 26 in 34.5% and 54.5% of patients, respectively, with no safety signal related to the treatment regimen. This supports further evaluation of combination therapy in CD. gov number: NCT02764762.

Mucosal Healing and Clinical Efficacy of Adalimumab in Small Intestinal Crohn's Disease (SIMCHA Study): Final Results From a Prospective, Open-Label, Single-Arm Study.

Endoscopic healing is a key treatment target in inflammatory bowel disease; few data are available on the clinical and endoscopic efficacy of biological therapy in upper gastrointestinal Crohn's disease. This study aimed to investigate small bowel mucosal healing and clinical efficacy of adalimumab therapy by video capsule endoscopy in patients with endoscopically active upper gastrointestinal Crohn's disease. This prospective, open-label, single-arm study included Crohn's disease patients with moderate-severe endoscopic proximal small bowel involvement, defined by a Lewis score >790. Patients were treated with adalimumab monotherapy for 24 weeks. Co-primary outcomes were endoscopic healing, defined as Lewis score <350, and endoscopic response, defined as >50% decrease in Lewis score. Secondary outcomes included clinical (Harvey-Bradshaw index <4) and biomarker remission (fecal calprotectin <250 μg/g, and C-reactive protein <5 mg/L). A total of 59 Crohn's disease patients were screened; 17 patients have met eligibility criteria and were enrolled. Endoscopic healing was observed in 8 patients (47.1%) and endoscopic response in additional 5 patients (29.4%) at 24 weeks. Median Lewis score was significantly decreased compared to baseline (1912 vs. 337, P = .0005). Eleven of 13 patients (84.6%) with clinical activity achieved clinical remission (baseline: 13/17 vs. week 24: 2/17, P < .0001). Nine of 10 patients with elevated C-reactive protein achieved normal C-reactive protein after treatment and the median C-reactive protein significantly decreased from 7.4 to 1.6 mg/L, P = .032. In contrast, no change was observed in fecal calprotectin pre- and posttreatment. Adalimumab induced endoscopic healing and clinical remission in patients with active small bowel Crohn's disease, with approximately half of the patients achieving endoscopic healing.

Adalimumab in conjunction with surgery compared with adalimumab monotherapy for hidradenitis suppurativa: A Randomized Controlled Trial in a real-world setting

Adalimumab, the only biologic registered for hidradenitis suppurativa, shows clinical response in up to 60% of patients, leaving many patients in need for other treatment options such as surgery. To compare the clinical effectiveness of adalimumab combined with surgery vs adalimumab monotherapy in patients with moderate to severe hidradenitis suppurativa. A pragmatic Randomized Controlled Trial was performed from August 2018 to July 2022. Primary outcome was the difference in mean International Hidradenitis Suppurativa Severity Score System reduction after 12months of treatment with the difference in mean Dermatology Life Quality Index reduction as a key secondary outcome. Thirty-one patients were included per arm. The mean International Hidradenitis Suppurativa Severity Score System at baseline was 23.9±10.7 in the surgery group and 20.9±16.4, in the monotherapy group. After 12months of treatment the surgery group had a significantly greater reduction in International Hidradenitis Suppurativa Severity Score System compared with the monotherapy group (-19.1±11.3 vs -7.8±11.8, P<.001). Moreover, the surgery group showed a greater reduction in Dermatology Life Quality Index after treatment compared with the monotherapy group (-8.2±6.2 vs -4 ± 7.7, P=.02). The study follow-up was too short to assess surgical recurrence rates. Combining adalimumab with surgery resulted in greater clinical effectiveness and improved quality of life after 12months in patients with moderate to severe hidradenitis suppurativa.

EFFECTIVENESS AND SIDE EFFECTS OF USING METHOTREXATE AND ADALIMUMAB IN THE TREATMENT OF RHEUMATOID ARTHRITIS PATIENTS

Rheumatoid arthritis (RA) is one of the diseases autoimmune systemic progressively characterized by inflammation of the membrane synovial that coating joints. Methotrexate (MTX) and Adalimumab are one of the drugs that are commonly used in Rheumatoid arthritis treatment. This study is aimed to look at the effectiveness and safety of both either in monotherapy and a combination of them. This study is a review of the article of experimental studies with data retrieval retrospectively on a database that has been set, namely PubMed, Google Scholar, and Portal Garuda were conducted for 6 mo. The use of adalimumab showed improvement based on the value DAS28-4(ESR) and HAQ-DI when compared with methotrexate. The side effects caused by MTX showed the risk was more than 2% than adalimumab. Several drug carriers are determinants of therapeutic efficacy, such as sRNA (small interfering-RNA), LPNP (hybrid lipid-polymers nanoparticles), FRβ (Folate-receptor β), NF-κB (nuclear factor kappa-light-chain-enhancer of activated B-cells), β-GP (β-Glycerophosphate). The use of adalimumab monotherapy has slightly better effectiveness than methotrexate but has more diverse side effects but less risk. The use of the combination does not have a significant difference, but the risk of side effects from both is lower than when used alone.

Outcome of adalimumab monotherapy in paediatric non-infectious uveitis

BackgroundAdalimumab in combination with other disease-modifying antirheumatic drugs (DMARD) such as methotrexate has a proven efficacy in the management of paediatric non-infectious uveitis. However, many children experience significant intolerance to methotrexate while on this combination, leaving a dilemma for clinicians for choosing the subsequent therapeutic roadmap. Continuation of adalimumab monotherapy might be an alternative feasible option under such settings. This study aims to investigate the efficacy of adalimumab monotherapy in paediatric non-infectious uveitis.MethodsChildren with non-infectious uveitis on adalimumab monotherapy (from August 2015 to June 2022) following intolerance to accompanying methotrexate or mycophenolate mofetil were included in this retrospective study. Data were collected at the initiation of adalimumab monotherapy and at three monthly intervals until the last visit. The primary outcome was to evaluate disease control on adalimumab monotherapy as determined by the proportion of patients who had less than a 2-step worsening in uveitis (as per SUN score) and no additional systemic immunosuppression during follow-up. Secondary outcome measures were visual outcome, complications and side-effect profile of adalimumab monotherapy.ResultsData was collected for 28 patients (56 eyes). The most common uveitis type and course were anterior and chronic uveitis respectively. Juvenile idiopathic arthritis-associated uveitis was the most common underlying diagnosis. During the study period, 23 (82.14%) of the study subjects met the primary outcome. On Kaplan–Meier survival analysis 81.25% (95% CI; 60.6–91.7%) children maintained remission at 12 months on adalimumab monotherapy.ConclusionContinuation of adalimumab monotherapy is an effective therapeutic option for the treatment of non-infectious uveitis in children who are intolerant to the combination of adalimumab and methotrexate or mycophenolate mofetil.

DOP85 Crohn's Disease Strictures Respond to Drug Treatment and Treat-to-Target Intense Combination Therapy is More Effective than Standard Anti-TNF Therapy. Two year results of the STRIDENT Randomised Controlled Trial.

Abstract Background The randomised STRIDENT (Stricture Definition and Treatment) trial showed that Crohn’s disease symptomatic strictures are responsive to anti-TNF therapy with most patients clinically improved after 12 months treatment with adalimumab +/- thiopurine. Treat to target intensification resulted in greater stricture morphology improvement. We present here 2 year (from study entry) follow up to assess response durability and risk of surgery. Methods Patients with symptomatic Crohn’s disease strictures and associated inflammation (elevated faecal calprotectin and CRP) were assessed with imaging (intestinal ultrasound and MRI) and ileo-colonoscopy. The Obstructive Symptom Score (OSS) was used for clinical assessment. Patients were randomised 2:1 to high dose adalimumab induction (160mg weekly for 4 weeks) followed by 40mg fortnightly plus thiopurine, with adalimumab dose increase at 4 and/or 8 months if evidence of ongoing inflammation, versus standard dose adalimumab monotherapy. The primary endpoint was improved OSS at 12 months. Patient interview was conducted at 24 months, assessing drug treatment, symptoms, need for endoscopic therapy, hospitalisation and surgery. Results In the initial 12 months study 52 patients were randomised to the intensive and 25 to the standard treatment arm. 64/77 (83%) patients recorded an outcome at 12 months (13/77 (17%) withdrawn: 8 surgery, 5 other) 74/77 (96.1%) patients were followed up at a mean of 25.3 (IQR 24.4-26.3) months. Of these, 59 (79.7%) remained on adalimumab, 10 (13.5%) had switched to another biologic and 5 (6.7%) had ceased biologic therapy. For patients who were on adalimumab at 12 months the risk of surgery by 24 months was 15%. Of patients on adalimumab 40mg fortnightly at 12 months, 12/48 (25%) had been dose escalated by 24 months. Endoscopic balloon dilatation, hospitalisation or surgery was required in 6 (8.1%), 14 (18.9%) and 13 (17.5%) respectively; rates were not different between the standard and intensive treatment groups (P = 0.982). Median time to intestinal resection was 12.2 (IQR 6.9-18.6) months. Clinical responders at 12 months, compared to non-responders, had a reduced likelihood of surgery at 24 months (9% vs 42%, P=0.003). Conclusion Clinical response to adalimumab for structuring Crohn’s disease is durable in a majority of patients, with most patients remaining on adalimumab and avoiding surgery at two years. Rates of surgery were not different between the standard and intensive therapy arms. Clinical response to adalimumab at 12 months is an important predictor of future surgical risk.

P749 Crohn’s disease stricture response and resolution with adalimumab therapy demonstrated with intestinal ultrasound. The STRIDENT randomised trial

Abstract Background Transmural healing is a treatment goal in the management of Crohn’s disease, and intestinal ultrasound (IUS) is potentially a sensitive, non-invasive and reproducible means to assess the response to treatment. Methods The STRIDENT (Stricture Definition and Treatment) study was a randomised controlled trial of standard dose monotherapy adalimumab versus intensive high-dose adalimumab combined with a thiopurine. Crohn’s disease patients with symptomatic intestinal strictures were randomised 2:1 to high dose adalimumab induction (160mg weekly for 4 weeks) with 40mg fortnightly maintenance plus thiopurine, with possible dose escalation at 4 and 8 months, versus standard dose adalimumab monotherapy. The primary endpoint was clinical response, defined as a reduction in the Obstructive Symptom Score (OSS) of ≥1, at 12 months. IUS was performed at baseline, 4, 8 and 12 months. IUS endpoints included stricture resolution (normalisation of pre-stenotic dilation (&amp;lt;2.5cm); reduced stricture bowel wall thickness (BWT ≥25% reduction); reduced colour doppler blood flow (inflammation, Limberg score ≤1) and normalisation of BWT (≤3mm). Patients with good quality baseline IUS and IUS-visible strictures were included for analysis. Results 77 patients underwent therapy randomisation. Of 63 patients with IUS-visible strictures 43 (68%) were in the intensive arm. Primary outcome was achieved by 32 (74%) patients in the intensive and 14 (70%) in the standard arms. Stricture resolution was seen in 1/5 non-responders and 18/45 responders. Median BWT reduced from 6.4mm (IQR 5.2-7.3mm) at baseline to 4.9mm (IQR 3-6mm) at 12 months (P&amp;lt;0.001). Clinical responders had significant reduction in median BWT from 6.0mm (IQR 4.5-7.1) at baseline to 4.3mm (IQR 3-5.7) at 12 months (P&amp;lt;0.001). There was no significant reduction in BWT at 4, 8 or 12 months in non-responders (P=0.26, P=0.29, P=0.26 respectively). BWT &amp;gt;3mm at 12 months occurred more often in non-responders than responders (P&amp;lt;0.05). Stricture resolution was seen in 13/36 in the intensive arm and 6/14 standard arm (P=0.75). The intensive arm had significant reduction in median BWT from 6.6mm (IQR 5.5-7.4mm) at baseline to 5.1mm (IQR 3-6.4mm) at 12 months (P&amp;lt;0.001). There was no significant reduction in BWT at 4, 8 or 12 months in the standard arm (P=0.75, P=0.42, P=0.09 respectively). There was no significant difference in BWT&amp;gt;3mm between trial arms at 12 months (P=1). Conclusion Stricture resolution and bowel wall thickness normalisation were demonstrated on intestinal ultrasound in stricturing Crohn’s disease patients treated with adalimumab therapy. Adalimumab therapy is associated with clinical improvement, and transmural improvement and healing, in patients with Crohn’s disease strictures.

P51 A service evaluation into the reduction of blood monitoring frequency during the COVID-19 pandemic

Introduction/BackgroundDue to the immense pressures placed on primary care services and the additional shielding advice for patients on immunosuppressive treatments at the beginning of the COVID-19 pandemic, the rheumatology team at this paediatric tertiary centre decided to decrease the blood monitoring frequency for paediatric rheumatology patients on adalimumab and etanercept monotherapy to 6 monthly from 3 monthly. This service evaluation aims to identify whether this change in monitoring frequency led to a negative impact on patient safety.Description/MethodA record of all relevant patients was obtained using WellSky® dispensing records. Filters were applied in order to be able to compare data in patients who were on the drugs for sufficient time (6 months) both pre and post change in monitoring frequency (defined as May 2020). Derangements in blood results (neutropenia, thrombocytopenia and liver function tests [LFTs]) were recorded, categorised (clinically significant = neutropenia <1 x 109/L, thrombocytopaenia <100 x 109/L, LFTs >3 fold upper limit of normal [ULN]) and compared. Adherence to suggested blood monitoring frequencies was evaluated pre and post change. It was deemed acceptable by the rheumatology team to be up to 1 month late for blood monitoringDiscussion/Results585 blood tests were performed across 96 patients between April 2019 and October 2021. There were 101 blood derangements in total (17%, 101/585). 54.5% (55/101) of derangements occurred pre change, with 14.5% (8/55) being classed as clinically significant. Of the derangements that occurred post change, only 6.5% (3/46) were clinically significant and were observed in one patient. All clinically significant derangements (pre and post change) were related to the LFTs. All clinically significant derangements were observed in adalimumab patients. More patients adhered to the monitoring frequency post change (71% post change vs 55% pre change). Patients who had experienced clinically significant derangements pre change, did not show any post change.Key learning points/ConclusionThis service evaluation has many limitations that impede drawing definite conclusions. For instance, other potential causes of LFT derangements were not recorded. Dose and frequency of administration of adalimumab and etanercept were also not recorded. Nonetheless, changing to 6 monthly monitoring does not appear to have had a negative impact on patient safety. It appears that an increased frequency of blood monitoring in these patients results in an increase detection of mild blood derangements. The incidence of clinically significant derangements in LFTs was reduced post change and clinically significant neutropaenia and thrombocytopaenia were not detected. Lower frequency of monitoring benefits both the NHS, patients and their families. We conclude that for the majority of patients on adalimumab or etanercept monotherapy, the benefits of 6 monthly monitoring outweigh any potential risks and we will continue to apply this approach to our patients in the future.

P276 Ixekizumab shows a pattern of pain improvement in patients with and without measurable inflammation in psoriatic arthritis

Abstract Background/Aims The efficacy of ixekizumab (IXE) and adalimumab (ADA) in patients with psoriatic arthritis (PsA) has been previously reported using ACR 50 and Psoriasis Area and Severity Index (PASI) 100 responses. To minimize confounding effects, in this analysis we assessed the efficacy of either IXE or ADA monotherapy on reduction of pain beyond measurable inflammation in patients with active PsA and low C-reactive protein (CRP) (&amp;lt;5mg/L) at baseline. Methods SPIRIT-H2H (NCT03151551) was a 52 week (W), multicenter, randomized, open-label, parallel-group, assessor-blinded study evaluating the efficacy and safety of IXE vs ADA. Participants were randomized (1:1) to approved-label dosing of IXE or ADA. This post-hoc analysis included only patients treated with IXE or ADA as monotherapy and with low CRP (&amp;lt;5mg/L) at baseline. Changes in joint pain were measured using PsA Patient’s Assessment of Pain Visual Analog Scale (VAS). We stratified patients into four categories by two measures of inflammation: 1. Sustained low inflammation either by a. CRP&amp;lt;5 mg/L during W4-24 or b. ≥50% improvement in swollen joint count (SJC) during W8-24. 2. Fluctuating inflammation either by a. CRP≥5 mg/L at least once between W4-24 or &amp;lt; 50% improvement in SJC at least once between W8-24. Results 95 monotherapy patients with a CRP &amp;lt;5mg/L at baseline were included in this analysis. Baseline characteristics were similar between both treatment arms. In patients with fluctuating inflammation as measured by CRP, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients at W16 (IXE: -31.64, ADA: -25.33) that was sustained up to W52 (IXE: -47.69, ADA: -20.67). There was significance in favor of IXE at W32 (p = 0.0045) and W52 (p = 0.0288). In patients with sustained low inflammation as measured by CRP, there was comparable improvement in joint pain between IXE and ADA-treated patients. In patients with sustained improvement in joint swelling as assessed by SJC, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients from W4 (IXE: -17.47, ADA: -10.42) that was sustained through W52 (IXE: -43.16, ADA: -32.62). In patients with fluctuating improvement in joint swelling as assessed by SJC, IXE-treated patients demonstrated a numerically greater mean improvement in joint pain VAS vs ADA-treated patients from W16 (IXE: -22.00, ADA: -19.31) that was sustained through W52 (IXE: -28.57, ADA: -13.27). Conclusion This analysis suggests a different pattern of pain improvement in patients with low baseline CRP treated with IXE or ADA monotherapy, with a favorable pain reduction outcome for IXE-treated patients, even when inflammation is fluctuating as measured by CRP or SJC improvement. This analysis supports the hypothesis that IXE improves joint pain in PsA patients with and without measurable inflammation. Disclosure N. Maney: None. K. de Vlam: Consultancies; Celgene, Eli Lilly and Company, Galapagos NV, Novartis, Pfizer, and UCB Pharma. Grants/research support; Celgene. G. Gallo: Shareholder/stock ownership; Eli Lilly and Company. P. Mease: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Galapagos NV, Gilead Sciences, GlaxoSmithKline. Member of speakers’ bureau; AbbVie, Amgen, Janssen, Novartis, Pfizer, and UCB Pharma. Grants/research support; Janssen, Merck Sharp &amp; Dohme, Neumentum, Novartis, Pfizer, Sun Pharma, and UCB Pharma. P. Rahman: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB Pharma. Grants/research support; AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, and UCB Pharma. V. Krishnan: Shareholder/stock ownership; Eli Lilly and Company. D. Sandoval Calderon: Shareholder/stock ownership; Eli Lilly and Company. C. Lin: Shareholder/stock ownership; Eli Lilly and Company. D. Zhu: Shareholder/stock ownership; Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; Eli Lilly and Company. P. Conaghan: Consultancies; Amgen, Bristol Myers Squibb, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Novartis, Pfizer, and UCB Pharma.

Long-Term Follow-up of Patients With Uveitis Treated With Adalimumab: Response Rates and Reasons for Discontinuation of Therapy

To evaluate the effectiveness and reasons for discontinuation including the side effect profiles of adalimumab in a real-world setting. Retrospective clinical cohort study. A medical chart review of clinical practice in 2 tertiary eye care services in Rotterdam, the Netherlands, was performed Data were collected from May 1, 2004, through September 1, 2020. Patients with noninfectious uveitis treated with adalimumab (n=341; 633 affected eyes) were included. The primary outcome was the effectiveness of adalimumab, measured by the number of patients achieving inactive disease, remission, and relapse-free survival. The secondary outcomes were the reasons for discontinuation, including side effects, and the number of patients who developed antibodies. In total, 341 patients were treated with adalimumab between May 2004 and September 2020. The uveitis recurrence-free survival interval was 3.4 years (range, 0-13 years). Adalimumab had an acceptable side effect profile. A total of 178 patients achieved inactive disease while continuing adalimumab, and 51 patients maintained remission after discontinuing adalimumab. Reasons for discontinuation of adalimumab were no response, relapse, or reasons unrelated to the effectiveness of treatment. Adalimumab antibodies were present in 40 of 115 patients (35%). Antibodies were associated with lower adalimumab levels, and antibodies were observed more often in patients on adalimumab monotherapy (P < .01). Adalimumab is effective for patients with noninfectious uveitis, with an acceptable side effect profile. Although relapses can occur, the majority of the patients achieved inactive disease or remission after cessation of adalimumab, without other systemic immunosuppressive medication.

Adalimumab with Methotrexate vs. Adalimumab Monotherapy in Psoriasis: First-Year Results of a Single-Blind Randomized Controlled Trial

Adalimumab is normally prescribed with methotrexate (MTX) in rheumatoid arthritis given the enhanced treatment effect and reduced antidrug antibody formation compared with adalimumab monotherapy (ADL). In psoriasis, the long-term treatment effects and pharmacokinetic profile have not been investigated extensively. We conducted a randomized controlled trial to assess the efficacy, safety, pharmacokinetics, and immunogenicity of adalimumab combined with MTX 10 mg per week (ADL-MTX group) compared with that of ADL (ADL group) in chronic plaque psoriasis. A total of 31 patients in the ADL-MTX group and 30 in the ADL group were analyzed. After 1 year, a (nonsignificant) better drug survival was found in the ADL-MTX group (74.2 vs. 58.6%, P= 0.15). The PASI 75 response in week 49 was 58.1 versus 36.7% (P= 0.13), and the median (interquartile range) serum-trough concentrations were 6.8 (5.5‒9.2) versus 5.9 (3.5‒8.8) mg/l (P= 0.26) in the ADL-MTX group and ADL group, respectively. Fewer patients showed antidrug antibodies in the ADL-MTX group (22.6 vs. 60.0%, P < 0.01). No serious adverse events occurred. Combination therapy of adalimumab and MTX results in fewer patients showing antidrug antibodies, with a trend toward a better PASI 75 response, drug survival, and higher serum-trough concentrations than ADL. Patient-reported outcomes and adverse events were comparable between the groups.

P622 Comparison of long-term outcomes of infliximab and adalimumab in biologic-naïve patients with ulcerative colitis

Abstract Background The comparative efficacy and safety of infliximab (IFX) and adalimumab (ADA) have revealed variable results in biologic-naïve patients with ulcerative colitis (UC), and long-term comparison studies between IFX and ADA with or without immunomodulator therapy are still needed in patients with UC. Methods The aim of this study was to evaluate the long-term effectiveness and safety of IFX compared to ADA in biologic-naïve adult patients with UC. All data of patients between June 2007 and March 2021 were collected retrospectively. We compared UC-related hospitalisation, colectomy, steroid use, and serious infections leading to treatment cessation. Results Out of 86 UC patients, 41 started IFX first (mean age at onset: 34.4 years, 61.0% male) and 45 started ADA first (mean age at onset: 31.4 years, 60.0% male). Disease duration was 7.2 years for IFX and 8.1 years for ADA. There were no significant differences between the two groups with respect to age, gender, smoking, extraintestinal manifestations, immunomodulator usage, or disease extent at the onset of anti-TNF therapy (p &amp;gt; 0.05). Concomitant rates of medication including mesalazine, sulphapyridine, thiopurine, and steroids were the same in both groups (p &amp;gt; 0.05). In the IFX group, baseline haemoglobin (11.7 vs 13.2, p = 0.05) and albumin (3.8 vs 4.2, p = 0.02) levels were lower than those of the ADA group, while C-reactive protein was higher (14.0 vs 6.0, p = 0.04) than in the ADA group. Total MAYO score at baseline was similar in both groups (p = 0.10). During anti-TNF therapy, steroid use was significantly higher in the ADA group (44.4%) compared to IFX (14.6%, p = 0.003). The rates of UC-related hospitalisation (IFX 9.8% vs ADA 13.3%, p=0.74) and colectomy (IFX 4.9% vs ADA 2.2%, p = 0.60) were similar in IFX and ADA groups. Serious infection leading to treatment cessation was not different between the two groups (IFX 2.4% vs ADA 4.4%, p=0.54). These outcomes were similar in UC patients treated with IFX or ADA monotherapy or in combination with an immunomodulator within each group, and there was no significant difference between IFX and ADA in combination with an immunomodulator regarding those outcomes (p &amp;gt; 0.05). Conclusion In this study, steroid use in the ADA group was significantly higher than in the IFX group, although UC-related hospitalisation, colectomy, and serious infections were not different in biologic-naïve adult patients with UC. We also observed that outcomes were similar in patients treated with IFX and ADA monotherapy or in combination with an immunomodulator. In the present study, IFX revealed better long-term outcomes for first-time treatment of UC patients.

P321 Mucosal Healing and Clinical remission after Treatment with Adalimumab in Small Intestinal Crohn’s Disease (SIMCHA study): final results from a prospective, open-label, single-arm study

Abstract Background Endoscopic mucosal healing is a key treatment target in inflammatory bowel disease (IBD). The aim of this study was to investigate small bowel (SB) mucosal healing using video capsule endoscopy (VCE) in patients with Crohn’s disease (CD) following, 24 weeks of adalimumab therapy. Methods In this prospective study, moderate to severe SB involvement CD patients were enrolled, defined by a Lewis score on VCE at diagnosis &amp;gt;, 790 in at least one tertile. All patients were treated with adalimumab monotherapy at the standard dosing for CD for, 24 weeks prior to undertaking the follow-up second VCE. The primary outcome was the endoscopic healing defined as a Lewis score (LS) &amp;lt;, 350, whereas partial response was defined as a &amp;gt;, 50% decrease from baseline in LS. Secondary outcomes included the remission in the clinical symptoms (Harvey Bradshaw Index, HBI &amp;lt;, 4) and biomarkers (fecal calprotectin, FC &amp;lt;, 200 ug/g, and c-reactive protein, CRP &amp;lt;, 5 mg/l). Results A total of, 59 CD patients were screened at McGill University Health Centre between November, 2011 and October, 2021;, 15 patients were met the eligibility criteria and were enrolled. The median age at inclusion was, 46 years (IQR, 28–51), 8 patients (53.3%) had ankylosing spondylitis. The most frequent locations of CD on VCE findings were the proximal-mid ileum (93.3%) and jejunum (73.3%). Primary outcome; complete endoscopic healing was observed in, 8 patients (53.3%, p=0.002, OR for remission = 2.14, 95%CI:, 1.25–3.68), and partial response in an additional, 5 patients (33.3%) after, 24 weeks. The median total Lewis score was decreased significantly compared to the baseline (1,912 vs., 337, p=0.0005). Secondary outcomes; the HBI at baseline was elevated (&amp;gt;, 4) in, 11 patients. Post-treatment HBI was consistent with clinical remission in all cases (11/15 vs., 0/15, p &amp;lt;0.0001 OR clinical remission = 0.27,95%CI:0.12–0.62). Nine patients who had baseline CRP elevation had achieved normal CRP after treatment, and the median CRP was significantly decreased from, 7.3 mg/L (1.8 -18.0) to, 1.6 mg/L (IQR, 1.0 –, 3.2), p=0.025. However, there were no significant changes in FC pre-and post-treatment. In addition, baseline VCE demonstrated ulcerated SB strictures in, 3 patients, 2 had non-ulcerated strictures on the second VCE. No capsule retention or other adverse events were observed. Conclusion Adalimumab led to significant improvement of small intestinal endoscopic healing in Crohn’s disease, with, 53% achieving complete healing.