Adalimumab In Combination Research Articles

Adopting adalimumab combined surgery in the management of moderate to severe hidradenitis suppurativa: Experience from a single medical center in southern Taiwan.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder primarily affecting the intertriginous and anogenital regions. Guidelines recommend various treatments for HS, including biologic agents like adalimumab for moderate to severe cases. Adalimumab is a type of human monoclonal IgG1 antibody designed to target tumor necrosis factor α. Recent studies have shown the effectiveness of adalimumab, either alone or combined with surgery, in managing HS. We retrospectively analyzed the medical chart of HS patients in a southern Taiwan medical center from 2019 to 2022 and investigated clinical features and treatment response. The institutional review board at Chang Gung Medical Foundation granted approval for the study. We primarily focused on moderate to severely affected patients. One hundred and two clinically diagnosed HS patients participated, with a male-to-female ratio of 2:1 and an average age of 31.8 at diagnosis. Among them, 41.2% were in Hurley stage III and 32.4% in stage II. Nineteen patients received excision with pre-surgical adalimumab; their average age at diagnosis was 31.1, with a gender ratio of 5.3:1. Surgery was most common on the buttocks (68%), axillae (21%), and groin (10%). Excision patients were primarily in advanced stages (Hurley III 94.7%, II 5.3%) with high body mass index. Adalimumab and surgery combined yielded a 68.4% improvement rate, while 15.8% remained stable and 15.8% did not respond as expected. In addition, smoking and obesity were prevalent among patients. Adalimumab showed promising results in moderate to severe HS, with significant improvement observed in our cases. The combination of adalimumab and surgery appeared effective in advanced HS patients with larger involved areas and more tunnels. No severe adverse events were reported. However, our study was limited by its retrospective nature and the lack of a control group. Despite these limitations, our study revealed the benefits of integrating adalimumab with suitable surgical procedures in managing patients experiencing moderate to severe HS in real-world scenarios.

A221 AZATHIOPRINE DOSING THRESHOLD IN ANTI-TNF COMBINATION THERAPY FOR MINIMIZING IMMUNOGENICITY AND OPTIMIZING TREATMENT EFFICACY FOR PATIENTS WITH INFLAMMATORY BOWEL DISEASE. A RETROSPECTIVE COHORT STUDY

Abstract Background Reported rates of anti-drug antibody (ADA) formation to tumor necrosis factor-a antagonists (anti-TNF) range from 20-75%. One way to reduce the risk of ADA formation is to combine a second immune-suppressing agent such as azathioprine (AZA) with the anti-TNF agent, known as combination therapy. However, it is unknown if the risk of combination therapy, including the additive risk of AZA and anti-TNF side effects, could be reduced by exposing individuals with inflammatory bowel disease (IBD) to the lowest dose of azathioprine while still maintaining the beneficial effect of ADA prevention. Aims To identify the minimum dose of AZA needed to prevent ADA formation to anti-TNF agents in individuals with IBD receiving combination therapy. We also assessed the occurrence of adverse drug events, treatment loss of response, treatment discontinuation and the need for treatment dose escalation. Methods A retrospective cohort study is ongoing in adult participants with IBDreceiving either infliximab or adalimumab in combination with AZA. Patients are divided based on their AZA dosage (low dose group, AZA ampersand:003C2mg/kg/day versus standard dose group, AZA 2mg/kg/day). All participants will be followed for 1 year and observed for the occurrence of ADA formation, adverse drug events, treatment loss of response, treatment discontinuation and the need for treatment dose escalation. Results To date, 48 participants are currently included (low dose, n=29; standard dose, n=19). 42 are on Infliximab and 6 are on Adalimumab. The occurrence of ADA was 17.4% in the low dose group and 20% in the standard dose group (pampersand:003E0.99). More participants lost response to treatment and discontinued anti-TNF therapy in the standard dose group (n=7/19, 36.8%) versus the low-dose group (n=8/29, 27.6%, p=0.54). More participants in the low-dose group received anti-TNF dose escalation (n= 20/29,68.9%) compared to the standard dose group (n=6/19, 31.6%, p=0.017). Adverse events, to Anti-TNF was seen in (n=3/19, 15.7%) in the standard dose group, in comparison to (n=4/29, 13.79%, pampersand:003E0.99) in the low dose group. Adverse events to AZA were surprisingly higher in the low dose group (n=14/29, 48.3%) while in the standard dose, it was (n=5/19, 26.3%, p=0.14). Conclusions The preliminary result of the study suggests that there is no significant difference in anti-drug antibody formation between standard and low doses of azathioprine in combination with anti-TNF therapy, in addition, data showed significant lower rates of Anti-TNF discontinuation and loss of response to treatment in low Azathioprine dose group. Completion of the study will help further define if low-dose AZA can be used for ADA prevention in anti-TNF combination therapy without compromising important clinical outcomes. Funding Agencies None

IMPROVEMENT IN GROWTH AND NUTRITION STATUS AFTER ANTI-TNF THERAPY INITIATION AMONG PATIENTS WITH PEDIATRIC CROHN’S DISEASE: RESULTS FROM THE COMBINE TRIAL

Abstract BACKGROUND Growth failure impacts 15-40% of children with Crohn’s disease (CD). Potential causes of growth failure include chronic inflammation, malabsorption, and poor nutritional intake. Control of inflammation is key to improving growth outcomes. Anti-TNF therapy has been associated with improved growth and nutritional status in affected children. Large studies of serial outcomes of growth after anti-TNF therapy initiation are limited. OBJECTIVE We sought to 1) describe baseline weight, height, and BMI status at anti-TNF initiation in children with CD in a large, multicenter clinical trial, 2) compare the demographic and clinical characteristics of children with and without weight, height, and BMI disturbance, and 3) describe follow-up anthropometric parameters at approximately 12 and 24 months after anti-TNF initiation. METHODS We analyzed data from the COMBINE trial, a multicenter study comparing infliximab or adalimumab in combination with oral methotrexate to anti-TNF monotherapy for children with CD. We obtained demographic, clinical, and anthropometric data at time of enrollment and after 12 and 24 months. Weight, height, and BMI Z-scores were dichotomized as normal (≥ -1) versus disturbance (< -1) at each time point. We used standard descriptive statistics to summarize the distribution of Z-scores and bivariate statistics to compare demographic, clinical, and treatment characteristics among participants with versus without growth disturbance at baseline. RESULTS Our study population included 199 children (25% female, 83% white, mean age 12 years). Of these, 53 (26.6%) had a weight disturbance at baseline (Table 1). Of 188 children with height data available at baseline, 52 (27.7%) had a height disturbance and 37 (19.7%) had a BMI disturbance. The mean short pediatric CD activity index (sPCDAI) was higher in those defined with weight, height, and BMI disturbance at baseline compared to those with normal parameters (Table 2). Gender, race, ethnicity, and age at time of anti-TNF initiation were not different between groups with and without weight, height, or BMI disturbances. Approximately 12 months after enrollment, the proportion of patients with height disturbance was 6.1% with a continued decrease to 0.9% at 24 months. BMI disturbance was observed in 7.5% of participants at 12 months and 2.8% at 24 months. Weight disturbance was observed among 5.7% and 0.8% of participants at 12 and 24 months respectively. DISCUSSION A substantial proportion of children with CD had weight, height, and BMI disturbance at time of anti-TNF initiation. These proportions decreased at approximately 12 months and 24 months, demonstrating significant improvement in growth disturbances after anti-TNF therapy. Table 1 % of children with weight, height, and BMI disturbance (Z-score <-1) at time of enrollment in addition to 12 and 24 months after anti-TNF therapy initiation. Table 2 Mean short pediatric Crohn’s disease activity index (sPCDAI) for BMI, weight, and height at time of anti-TNF initiation.

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.

Comparison of biologic monotherapy versus biologic and disease-modifying anti-rheumatic drug combination in the treatment of non-systemic juvenile idiopathic arthritis

Purpose To explore the efficacy of biologics as mono- or combination therapy with conventional disease modifying anti-rheumatic drugs (cDMARDs) in the treatment of juvenile idiopathic arthritis (JIA). Material and Methods Medical records of patients with JIA followed-up from January 2020 to 2023 who were treated either with biologic drugs as monotherapy or with combination of cDMARD were reviewed retrospectively. Data of demographic features, clinical scores and treatments were assessed. Results Two hundred five cases received etanercept, adalimumab, or tocilizumab alone or in combination with a cDMARD for JIA were included. The male to female ratio of the cohort was almost equal. Oligoarticular was the most common subtype of JIA. Majority (n=128, 62.4%) of the group received biologic drugs as monotherapy, while the remaining third (n=77, 37.6%) used a combination of biologic and a cDMARD. Nearly half of the group (57.1%) were treated with etanercept and etanercept monotherapy was the most commonly used one among all JIA subtypes except juvenile psoriatic arthritis. Adalimumab combination therapy was prescribed in most of the children with juvenile psoriatic arthritis. Adalimumab, alone or in combination with methotrexate, was preferred for all 8 patients with uveitis at the onset of the disease. Adalimumab combined (n=9) and tocilizumab monotherapy (n=4) were the most common biologics in those who developed uveitis during follow-up. Conclusion Etanercept, adalimumab, or tocilizumab are effective and safe biologics in treatment of JIA. Considering their cost-effective properties, choosing biologic drugs timely as combined or monotherapy is effective in preventing early and late sequelae of JIA.

APOA4 as a novel predictor of prognosis in Stevens-Johnson syndrome/toxic epidermal necrolysis: A proteomics analysis from two prospective cohorts

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening adverse drug reactions. Conventional systemic therapies are of limited efficacy and often exhibit strong side effects. To assess the efficacy and safety of the combination treatment with a tumor necrosis factor-α antagonist adalimumab and delineate the underlying mechanisms. We evaluated the efficacy and safety of the combination therapy with adalimumab by comparing 2 treatment cohorts of SJS/TEN patients. Patient plasma samples were collected for proteomics analysis. The combination therapy with adalimumab significantly shortened the time to mucocutaneous re-epithelization and healing, with reduced side effects caused by corticosteroids. Plasma proteomic profiling showed that apolipoprotein A-IV (APOA4) was one of the most significant differentially expressed proteins. Multivariate regression analysis revealed that APOA4 level was significantly associated with prognosis parameter of SJS/TEN (P=.004), but not with disease severity score (severity-of-illness score for toxic epidermal necrolysis [SCORTEN]) (P=.118). Thus further research will be helpful to effectively incorporate APOA4 into current SCORTEN-driven protocols. The cohort size is relatively small. Both cohorts had low overall SCORTEN scores. Adalimumab in combination with corticosteroids demonstrates significant clinical benefits over corticosteroids alone in SJS/TEN patients. Moreover, APOA4 may serve as a novel prognostic marker of SJS/TEN.

Proof-of-Concept Double-Blind Placebo-Controlled Trial Measuring Cartilage Composition in Early Rheumatoid Arthritis under TNF-α-Inhibitor Therapy

Low levels of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) values are indicative of cartilage degeneration. Patients with early rheumatoid arthritis are known to have low dGEMRIC values due to inflammatory activity. The additional effect of biological disease-modifying antirheumatic drug (bDMARD) and conventional synthetic disease-modifying antirheumatic drug (csDMARD) treatment on cartilage status is still unclear. In this prospective, double-blinded, randomized proof-of-concept clinical trial, patients with early rheumatoid arthritis (disease duration less than 12 months from symptoms onset) were treated with methotrexate + adalimumab (10 patients: 6/4 (f/m)). A control group with methotrexate alone (four patients: 2/2 (f/m)) was used. Cartilage integrity in the metacarpophalangeal joints was compared using dGEMRIC at baseline, 12, and 24 weeks after treatment initiation. A statistically significant increase in dGEMRIC levels was found in the adalimumab group considering the results after 12 and 24 weeks of therapy (p < 0.05) but not in the control group (p: non-significant). After 24 weeks, a tendency towards increased dGEMRIC values under combination therapy was observed, whereas methotrexate alone showed a slight decrease without meeting the criteria of significance (dGEMRIC mean change: +85.8 ms [-156.2-+346.5 ms] vs. 30.75 ms [-273.0-+131.0 ms]; p: non-significant). After 24 weeks of treatment with a combination of methotrexate and adalimumab, a trend indicating improvement in cartilage composition is seen in patients with early rheumatoid arthritis. However, treatment with methotrexate alone showed no change in cartilage composition, as observed in dGEMRIC sequences of metacarpophalangeal joints.

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.

Successful treatment of a child's generalized pustular psoriasis with adalimumab in combination with low-dose acitretin.

Successful treatment of a child's generalized pustular psoriasis with adalimumab in combination with low-dose acitretin.

Dual Biologic Therapy in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Retrospective Study.

Inflammatory bowel diseases in children are characterized by a wide variety of symptoms and often a severe clinical course. In the treatment, we aimed to induce and maintain remission. We focused on assessing the efficacy and safety of the concomitant use of two biologic therapies including: anti-TNF (infliximab, adalimumab) vedolizumab and ustekinumab in a refractory pediatric IBD cohort. Fourteen children (nine ulcerative colitis, one ulcerative colitis/IBD-unspecified, four Crohn's disease) with a disease duration of 5.2 (8 months-14 years) years, initiated dual therapy at an age of 11.7 (3-17) years after failure of monotherapy with a biological drug. Five patients (36%) were treated with vedolizumab/adalimumab (VDZ + ADA), five (36%) with ustekinumab/adalimumab (UST + ADA), and three (21%) with infliximab/vedolizumab (IFX + VDZ). One patient (7%) was switched from a combination of vedolizumab and adalimumab to ustekinumab and adalimumab during follow-up. A clinical improvement was obtained in ten children (73%; 5 UC, 1 UC/IBD-unspecified, 4 CD) on the PCDAI/PUCAI scale after 4 months of a second biological drug being added. The median fecal calprotectin decreased from 1610 µg/g (140-10,100) to 586 µg/g (5-3410; p = 0.028) between baseline and 4 months. Our clinical experience suggests that dual therapy may be an option for pediatric patients with moderate and severe courses of IBD with limited therapeutic options.

S2789 A Rare Triad of Ulcerative Colitis, Large Vessel Vasculitis and Celiac Disease

Introduction: Inflammatory bowel disease (IBD) has been associated with large-vessel vasculitis (LVV), with the diagnosis of IBD preceding that of LVV by years. We present for the first time in known literature a triad of concurrent ulcerative colitis (UC), aortitis and celiac disease. Case Description/Methods: A 58 year old Hispanic man with a history of hypertension and gout presented with two weeks of intractable temporomandibular headaches, and two months of non-bloody diarrhea and weight loss. Physical exam was unremarkable. Labs showed hemoglobin 6.9 g/dL, erythrocyte sedimentation rate 120 mm/hr, C-reactive protein 281 mg/dL and IgA tissue transglutaminase antibody 23 U/mL. ANA, C3, C4, proteinase-3 and myeloperoxidase antibodies were within normal limits. Colonoscopy showed pancolitis from rectum to ascending colon. The terminal ileum was normal. Abdominal MRI found aortic wall hyperintensity from the renal arteries to common iliac bifurcation. CT angiogram showed wall thickening of the left carotid artery, aortic arch, descending thoracic and abdominal aorta, consistent with vasculitis. Patient was given stress dose steroids with improvement in headache and normalization of ESR and CRP. Temporal artery biopsy was unremarkable. Four months after hospitalization, repeat colonoscopy with duodenal biopsies for celiac disease revealed mild increase in intraepithelial lymphocytes with preserved villous architecture. He was started on a gluten free diet and adalimumab in combination with methotrexate for UC and LVV. Discussion: About 10 case reports of patients with both UC and either Takayasu (TAK) or giant cell arteritis (GCA) have been described, with UC typically diagnosed 15-45 years before the vasculitis. Vasculitis in the GI tract can mimic IBD, making colonoscopy and biopsy crucial for diagnosis. HLA haplotypes A24, B52, and DR2 are associated with both UC and aortitis and Interleukin-9, observed in temporal arteritis lesions, may be implicated in the pathogenesis of UC. Shared chromosomal variants between patients with UC and celiac disease may explain why IBD risk is up to 9-fold higher in patients with celiac disease. Our patient may have presented with isolated aortitis or an early form of GCA. Methotrexate is used to treat LVV and is combined with an anti-TNF agent to treat UC, as in our case. This is the first known report of co-occurring UC, celiac disease and aortitis; however, whether the three inflammatory conditions are mechanistically related warrants further research.

Evidence for Anti-inflammatory Effects of Adalimumab in Treatment of Patients With Major Depressive Disorder: A Pilot, Randomized, Controlled Trial.

Literature has suggested that major depressive disorder (MDD) is accompanied by higher concentrations of inflammatory biomarkers, which could sabotage response to conventional treatments. This study aimed to evaluate the efficacy and safety of adalimumab adjunct to sertraline in adults with MDD and increased levels of systemic inflammation. In a 6-week, randomized, double-blind, placebo-controlled trial, 36 patients with MDD and high-sensitivity C-reactive protein ≥3 mg/L were equally assigned to receive sertraline plus either adalimumab or placebo. Participants were assessed using the Hamilton Depression Rating Scale (HAM-D) at baseline, week 3, and week 6. Moreover, serum concentrations of inflammatory biomarkers were measured at baseline and trial end point. Finally, patients were assessed for any adverse event during the trial. Fifteen patients in each group completed the trial course. All baseline characteristics of participants were similar between the groups. Adalimumab adjunct to sertraline resulted in a greater improvement in HAM-D score compared with placebo over the trial period ( P < 0.001). Participants receiving adalimumab significantly experienced greater response to treatment (≥50% reduction in the HAM-D score) than those receiving placebo ( P = 0.042). Furthermore, after 6 weeks of adalimumab combination therapy with sertraline, inflammatory biomarkers significantly decreased ( P ≤ 0.001), whereas no significant alteration was found in the placebo group. No serious adverse event was documented in the treatment arms. Adalimumab adjunctive therapy remarkably improves depressive symptoms of patients with MDD. Further investigations with larger sample sizes and longer follow-up periods are required to confirm the findings.

Efficacy and safety of biologic therapy in microscopic colitis: systematic review and meta-analysis.

This systematic review and meta-analysis sought to evaluate the effectiveness and safety of biologic therapy in the treatment of steroid-refractory microscopic colitis (MC). We searched MEDLINE, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on biologic use (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) for induction and maintenance of remission in MC. We assessed clinical remission and response rates and all reported adverse events (AEs). A total of 376 studies were screened yielding 13 articles (including four abstracts) with a combined information on 78 patients for efficacy and safety outcomes. Most studies were case series. Vedolizumab was used in five studies, adalimumab in three, and a combination of infliximab and adalimumab in five studies. The rates of remission were 66.08% (95% CI, 36.79-95.37%; I2 , 71%) at weeks 3-6 and 54.20% (95% CI, 39.39-69.01%; I2 , 0%) at weeks 12-16. Clinical response rates were 100% (95% CI, 88.04-100%; I2 , 0%) at weeks 3-6 and 67.20% (95% CI, 47.72-86.69%; I2 , 52%) at weeks 12-16. Most frequent AE was medication discontinuation with a pooled incidence of 16.1% (95% CI, 5.9-37.5%). No deaths attributable to biologic use were reported. The overall quality of evidence was very low due to the high risk of biases. Low-quality evidence supports the short-term efficacy of biologics in budesonide refractory MC. While our findings represent the most comprehensive evaluation of biologic therapy in severe MC, further research including randomized clinical trials is needed to better define the role of specific agents and long-term therapy.

Research priority setting for paediatric rheumatology in the UK.

The evidence base that underlies the management of children and young people with paediatric rheumatic diseases is deficient. In this field, there are many crucial unanswered questions. The UK Paediatric Rheumatology Clinical Studies Group, supported by UK National Institute for Health Research Clinical Research Network: children and Versus Arthritis, elicited ideas for research priorities from paediatric rheumatologists, trainees, allied health-care professionals, nurse specialists, patients, parents of patients, carers, and charities. These ideas were collected through online surveys and face-to-face meetings. A modified Delphi process was used, which included online research priority ranking surveys and a consensus workshop. A longlist of 55 disease-specific research priorities and 37 general research priorities were voted on in the first survey. A list of 11 top general research priorities was produced. The top ten disease-specific research priorities were discussed in depth at a Delphi workshop to determine their final ranking. This Health Policy paper will help to guide clinicians, academics, and funding bodies to prioritise research in paediatric rheumatic diseases, specifically in areas of unmet patient needs.

Combined moxibustion/adalimumabin treatment of ankylosing spondylitis, and its influence on related functional indicators

Purpose: To study the clinical efficacy of the combination of du-moxibustion and adalimumab in the treatment of ankylosing spondylitis, as well as its influence on related functional indicators.Methods: From 2019 to 2020, 90 ankylosing spondylitis patients treated in Shandong Traditional Chinese Medicine University Hospital were assessed for eligibility and recruited. They were assigned, based on the order of admission, to receive either conventional treatment (control group) or dumoxibustion plus adalimumab (study group). Clinical treatment efficacy, levels of inflammatory indices, and spinal mobility in the two groups were determined and compared. Numerical Rating Scale (NRS) was employed for pain assessment, while Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used for disease status evaluation. Bath Ankylosing Spondylitis Functional Index (BASFI) was used for assessing functional limitation.Results: Du-moxibustion plus adalimumab was associated with significantly higher treatment efficacy and lower levels of inflammatory factors when compared to conventional treatment (p &lt; 0.05). Comparable NRS scores before treatment and 2 weeks after treatment were observed in the two groups (p &gt; 0.05). The eligible patients given du-moxibustion plus adalimumab showed lower NRS scores, higher BASDAI scores, and lower BASFI scores versus those receiving conventional treatment (p &lt; 0.001).Conclusion: Treatment of ankylosing spondylitis patients with the combination of du-moxibustion and adalimumab mitigates symptoms and clinical indicators of the disease and relieves pain in the patients. Therefore, the combined treatment should be subjected to further clinical trials prior to its use in clinical practice.

Adalimumab for the Treatment of Pediatric Populations With Non-Infectious Uveitis

&#x0D; Two systematic reviews, 1 economic evaluation, and 2 evidence-based guidelines were identified regarding the clinical effectiveness (including safety), cost-effectiveness, and use of adalimumab in pediatric populations with non-infectious uveitis.&#x0D; Pooled data of the SYCAMORE and ADJUVITE randomized controlled trials comparing adalimumab to placebo demonstrated that adalimumab significantly increased the likelihood of reducing or interrupting corticosteroid use (which is beneficial as long-term corticosteroid use can result in cataracts and glaucoma). Adalimumab significantly increased the event of a satisfactory response rate, but there was no difference in safety assessed as systemic adverse events and local adverse effects.&#x0D; Specific to the ADJUVITE trial, visual acuity slightly worsened before and after treatment with adalimumab and it was unclear if adalimumab increased control of intraocular inflammation.&#x0D; Specific to the SYCAMORE trial, adalimumab significantly lowered the risk of treatment failure and the rate and number of adverse events and serious adverse events were higher in the adalimumab group compared to the placebo group. For the adalimumab group, the most common adverse event type was infections and infestations and the most common serious adverse events were glaucoma, cataracts, injection site reactions, arthritis, and arthralgia.&#x0D; In the perspective of the health care system in the UK, adalimumab plus methotrexate was not found to be cost-effective compared to methotrexate alone (modelled by placebo data) in uveitis associated with juvenile idiopathic arthritis.&#x0D; Cost-effectiveness analyses of adalimumab at a discounted price lowered the incremental cost-effectiveness ratio, which supports the potential use of biosimilars in the future due to cost savings.&#x0D; Both guidelines recommended the use of treatment that blocks proteins that cause inflammation (tumour necrosis factor-alpha inhibitors) such as adalimumab in combination with an immunosuppressive agent such as methotrexate (i.e., adalimumab plus methotrexate) in patients with uveitis associated with juvenile idiopathic arthritis who are not responsive to initial treatment (e.g., topical corticosteroids) and are at risk for severe uveitis or vision threatening complications.&#x0D; The American College of Rheumatology/ Arthritis Foundation recommended the use of adalimumab and infliximab over etanercept with no preference between adalimumab and infliximab. Conversely, the guideline from multiple interdisciplinary German groups recommended that adalimumab and infliximab are the first- and second-choice tumour necrosis factor-alpha inhibiting drugs, respectively. They recommended a treatment switch to infliximab then golimumab when adalimumab is not effective or there is treatment failure with adalimumab.&#x0D;

Combining biological therapies in patients with inflammatory bowel disease: a Finnish multi-centre study

Background and aims Therapy with two concomitant biologicals targeting different inflammatory pathways has emerged as a new therapy option for treatment refractory inflammatory bowel disease (IBD). Data on the efficacy and safety of dual biological therapy (DBT) are scarce and are investigated in this study. Materials and methods Data on all patients treated with a combination of two biologicals in four Finnish tertiary centres were collected and analysed. Remission was assessed by a physician on the basis of biomarkers, endoscopic evaluation and alleviation of symptoms. Results A total of 16 patients with 22 trials of DBT were included. Fifteen patients had Crohn’s disease. The most common combination of DBT was adalimumab (ADA) and ustekinumab (USTE; 36%) with median follow-up of nine months (range 2–31). Altogether seven (32%) patients were in remission at the end of follow-up and in two trials response to DBT was assessed to be partial with the relief of patient symptoms. In a total of four trials DBT reduced the need for corticosteroids. The majority of patients achieving a response to DBT were treated with the combination of ADA and USTE (56%). At the end of follow-up all nine (41%) patients responding to DBT continued treatment. Infection complications occurred in three patients (19%). Conclusion DBT is a promising alternative treatment for refractory IBD, and half of our patients benefitted from it. More data on the efficacy and safety of DBT are needed especially in long-term follow up.

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.

Clinical Characteristics and Efficacy of Adalimumab and Low-Dose Methotrexate Combination Therapy in Patients With Vogt-Koyanagi-Harada Disease.

This retrospective study investigated the clinical characteristics and efficacy of adalimumab and low-dose methotrexate combination therapy in patients with Vogt–Koyanagi–Harada disease who were treated at Hiroshima University from February 2012 to May 2021. The patients' demographics, clinical features at administration of immunosuppressive therapy, steroid-sparing immunosuppressive therapy, side effects, and relapses were recorded. The efficacies of steroid-sparing immunosuppressive therapy (methotrexate, cyclosporine A, adalimumab, and adalimumab and methotrexate combination therapy) were analyzed. Among 62 patients, the median age at diagnosis was 47 years and the median duration of uveitis was 51 months. Systemic corticosteroid therapy was administered to 93.5% of patients (n = 58). Thirty-four patients (54.8%) were treated with steroid-sparing immunosuppressive therapy. Methotrexate and cyclosporine A were administered to 12 and 22 patients, respectively; relapse occurred in 50.0% and 22.7% of the patients, respectively. Discontinuation of cyclosporine A was required in 63.6% of patients because of side effects. Adalimumab was administered to 14 patients. Recurrence occurred in 11 patients, requiring methotrexate concomitantly. The mean dose of methotrexate at inflammatory quiescence after side effect-related dose decrease was 8.0 mg/week (0.13 mg/kg). The median duration of combination therapy without recurrence was 20 months. There were no serious adverse events during adalimumab therapy. A high relapse rate was observed in patients receiving methotrexate; a high rate of side effects requiring discontinuation was observed in patients receiving Cyclosporine A. Patients with late-stage Vogt–Koyanagi–Harada disease may achieve better control with adalimumab and methotrexate combination therapy.

P012 Efficacy of Exclusive Enteral Nutrition and Weekly Adalimumab Combination in Crohn's Patients With Fibroinflammatory Stenosis.

Clinical remission can be achieved with exclusive enteral nutrition (EEN) in patients with Crohn's Disease with different sites of involvement, varying severity, and complications such as abscess and fistula. In the CHARM study, weekly or every other week administration of adalimumab (ADA) did not provide a significant difference in remission rates. Nevertheless, the subgroup analysis showed that in patients with anti-TNF experience, moderate-to-severely active disease, and high CRP values, rates of remission were significantly higher with weekly doses. Our aim was to determine the efficacy of EEN and weekly adalimumab combination in Crohn's patients with fibroinflammatory stenosis. Seven consecutive patients with newly diagnosed severe disease and fibro-inflammatory stenosis were included in this retrospective study. The PRO-2 score was used to assess clinical remission, the SES-CD score to determine the severity of endoscopic activity, the Nancy score to determine the severity of inflammation in tissue samples, and the MaRIA score to determine changes in magnetic resonance enterography (MRE). Nestle Modulen® (35kcal/kg) was used for twelve weeks as the EEN solution. In addition to the formulation, patients were only allowed to consume water. At the end of the 12th week, the patients gradually switched to a standard diet. Concomitantly initiated ADA was continued at 40 mg weekly after standard loading doses of 160 mg-80 mg-40 mg. The patients were evaluated with clinical and laboratory findings at the 1st, 4th and 8th weeks of the treatment, and also with colonoscopy and MRE at the 12th week. The difference between mean PRO-2 score (24.7 ± 1.97, 20.1 ± 1.63, 15.3 ± 1.81,11.4 ± 2.15, 5 ± 1.1, p = 0.031), CRP (14.3 ± 4.54, 11.2 ± 3.31, 6.92 ± 2.88, 2.16 ± 1.14, 0.25 ± 0.13, p = 0.022), albumin (2.9 ± 0.21, 3.05 ± 0.33, 3.4 ± 0.29, 4.1 ± 0.45, 4.6 ± 0.27, p = 0.044), hemoglobin (11.38 ± 0.97, 12.65 ± 0.87, 13.41 ± 0.91, 13.89 ± 0.76, 14.44 ± 0.65, p = 0.063), SES-CD score (17.14 ± 4.87, 7.66 ± 5.98, p = 0.014), MaRIA score (21.13 ± 7.42, 9.91 ± 4.55, p = 0.003) and Nancy score (3.71±0.48, 1.71±0.36, p=0.028) were all statistically significant. The stenotic segment endoscopically passed at week 12 in every patient but one, which had minimally invasive surgery (ileoascendostomy) because of ileus that developed at the eighth week of therapy. Of note, the patient who underwent surgery had perianal involvement. Despite the extremely limited number of patients and short-term follow-up results, 12-week EEN and concurrent weekly ADA therapy may be effective in inducing remission in this group of patients. There is a need for large-scale, prospective studies on this subject.