Efficacy Of Adalimumab Research Articles

Comparison of the efficacy and safety of tocilizumab, sarilumab, and sirukumab in comparison with adalimumab as monotherapy in patients with active rheumatoid arthritis: ABayesian network meta-analysis of randomized controlled trials.

The relative efficacy and tolerability of tocilizumab, sarilumab, and sirukumab as monotherapy were assessed and compared with those of adalimumab in patients with rheumatoid arthritis (RA) who were intolerant to or responded inadequately to methotrexate (MTX). We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tocilizumab, sarilumab, and sirukumab, and adalimumab in RA patients who are intolerant to or show an inadequate response to MTX. Three RCTs comprising 1,066 patients met the inclusion criteria. Tocilizumab 8 mg monotherapy was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the ACR20 response rate. Compared with adalimumab, tocilizumab, and sarilumab as monotherapy showed significantly higher ACR20 response rates. Ranking probability based on SUCRA indicated that tocilizumab 8 mg had the highest probability of being the best choice for achieving ACR20 response rate, followed by sarilumab 200 mg, adalimumab 40 mg, and sirukumab 50 mg. Moreover, the ACR50 response rate showed a similar distribution pattern to that of ACR20. Regarding adverse events, the ranking probability based on SUCRA indicated that sarilumab 200 mg was possibly the safest, followed by adalimumab 40 mg, tocilizumab 8 mg, and sirukumab 50 mg. However, the number of patients who experienced serious adverse events did not differ significantly between these biologics. Based on ACR20 and ACR50 response rates, monotherapy with tocilizumab 8 mg, followed by sarilumab and sirukumab monotherapy, was optimal for patients with RA responding inadequately to MTX or showing intolerance.

Adalimumab in patients with vision-threatening uveitis: real-world clinical experience

ObjectivesBiologics are rapidly emerging as an effective vision saving addition to systemic uveitis therapy. The aim of this multicentre retrospective study is to review the outcomes of a large group...

Skin advanced glycation end products as a diagnostic and monitoring tool among psoriatic patients: how the therapy helps reduce cardiovascular disease risk.

Psoriasis is a disturbing and burdensome inflammatory skin disorder, with a global prevalence of 2-3%. An increased risk of cardiometabolic disease between psoriatic patients has been recently demonstrated. This is probably due to the psoriasis systemic inflammation and the increased levels of inflammatory cytokines, such as IL-17, IL-23, and TNF-α. Advanced glycation end products (AGEs) are the products of nonenzymatic glycation and oxidation of proteins and lipids which modify their structure and function. They have a significant role in the pathogenesis of diabetic nephropathy, atherosclerosis, and cardiovascular diseases of diabetic adults and children. The accumulation of AGEs can be measured by skin autofluorescence (SAF). Adalimumab (Humira ®) is a fully human monoclonal antibody, administered via subcutaneous injection, which binds the tumor necrosis factor (TNF) and is used to treat moderate-to-severe chronic plaque psoriasis. We performed an observational prospective study of 24 weeks to assess the reduction of AGEs through SAF measurement during treatment with adalimumab. SAF measurements in patients were performed at T0 and after 24 weeks of therapy. Adalimumab efficacy was assessed using Psoriasis Area and Severity Index (PASI), Visual Analogue Scale (VAS) for pain, and erythrocyte sedimentation rate (ESR). ESR, AGEs, PASI, and VAS for pain decreased throughout the study period. Adalimumab reduced AGEs in psoriatic patients. Biologic therapies may also prevent cardiovascular disease, suggesting a new approach of combined therapy for psoriasis and cardiovascular diseases.

Efficacy and Safety of Adalimumab in Conjunction With Surgery in Moderate to Severe Hidradenitis Suppurativa

Surgery is a mainstay in the management of hidradenitis suppurativa (HS). Adalimumab is the first drug approved for HS. To investigate the efficacy and safety of adalimumab in combination with wide-excision surgery followed by secondary intention healing. The Safety and Efficacy of Adalimumab for Hidradenitis Suppurativa Peri-Surgically (SHARPS) trial was a phase 4, randomized, double-blind, placebo-controlled study of adalimumab in conjunction with surgery. Patients were enrolled in 45 sites across 20 countries from July 18, 2016, to February 2, 2019, with the last patient visit on October 16, 2019. Eligible patients (aged 18-65 years) had moderate to severe HS that required radical surgery in an axillary or inguinal region and had 2 other anatomical regions affected, with 1 or more regions at Hurley stage II or III. Analysis was conducted in November 2019. Patients were randomized 1:1 to receive continuous adalimumab, 40 mg, or placebo during presurgery (12 weeks), perioperative (2 weeks), and postoperative (10 weeks) periods. The primary end point was the proportion of patients achieving HS clinical response across all body regions at week 12. Overall, 103 patients were randomized to adalimumab and 103 to matching placebo. Among all patients, 51% (n = 106) were women, 94% (n = 193) were White, and the mean (SD) age was 37.6 (11.3) years. At week 12, significantly more patients receiving adalimumab (49 of 103 [48%]) vs placebo (35 of 103 [34%]; P = .049) achieved HS clinical response across all body regions (treatment difference, 14% [95% CI, 0%-27%]). Treatment-emergent adverse events were reported in 74 of 103 patients (72%) and 69 of 103 patients (67%) in the adalimumab and placebo groups, respectively. No increased risk of postoperative wound infection, complication, or hemorrhage was observed with adalimumab vs placebo. Two deaths occurred in the adalimumab group; neither was considered as having a reasonable possibility of relationship to study drug. Adalimumab was efficacious in conjunction with wide-excision surgery followed by secondary intention healing, with no need to interrupt treatment prior to surgery. These data support further investigation of adalimumab as an adjuvant therapy to surgery in patients with moderate to severe HS. ClinicalTrials.gov Identifier: NCT02808975.

26248 Efficacy of secukinumab and adalimumab in psoriatic arthritis patients with moderate-to-severe plaque psoriasis: Results from the EXCEED study

Introduction: The EXCEED study investigated whether secukinumab is superior to adalimumab in biologic-naïve, active psoriatic arthritis (PsA) patients with active plaque psoriasis (PsO).

775d Ustekinumab Versus Adalimumab for Induction and Maintenance Therapy in Moderate-to-Severe Crohn’s Disease: The SEAVUE Study

Head-to-head trials are important to inform patient (pt) and physician choice. We studied the efficacy and safety of ustekinumab (UST) vs adalimumab (ADA) through 1 year in biologic-naïve pts with moderate-to-severe Crohn’s disease (CD).

Clinical outcomes and predictors of response for adalimumab in patients with moderately to severely active ulcerative colitis: a KASID prospective multicenter cohort study.

Background/AimsThis study assessed the efficacy and safety of adalimumab (ADA) and explored predictors of response in Korean patients with ulcerative colitis (UC).MethodsA prospective, observational, multicenter study was conducted over 56 weeks in adult patients with moderately to severely active UC who received ADA. Clinical response, remission, and mucosal healing were assessed using the Mayo score.ResultsA total of 146 patients were enrolled from 17 academic hospitals. Clinical response rates were 52.1% and 37.7% and clinical remission rates were 24.0% and 22.0% at weeks 8 and 56, respectively. Mucosal healing rates were 39.0% and 30.1% at weeks 8 and 56, respectively. Prior use of anti-tumor necrosis factor-α (anti-TNF-α) did not affect clinical and endoscopic responses. The ADA drug level was significantly higher in patients with better outcomes at week 8 (P<0.05). In patients with lower endoscopic activity, higher body mass index, and higher serum albumin levels at baseline, the clinical response rate was higher at week 8. In patients with lower Mayo scores and C-reactive protein levels, clinical responses, and mucosal healing at week 8, the clinical response rate was higher at week 56. Serious adverse drug reactions were identified in 2.8% of patients.ConclusionsADA is effective and safe for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF-α therapy. The ADA drug level is associated with the efficacy of induction therapy. Patients with better short-term outcomes were predictive of those with an improved long-term response.

Efficacy of secukinumab and adalimumab in patients with psoriatic arthritis and concomitant moderate-to-severe plaque psoriasis: results from EXCEED, a randomized, double-blind head-to-head monotherapy study.

SummaryBackgroundSecukinumab [an interleukin (IL)‐17A inhibitor] has demonstrated significantly higher efficacy vs. etanercept (a tumour necrosis factor inhibitor) and ustekinumab (an IL‐12/23 inhibitor) in patients with moderate‐to‐severe plaque psoriasis.ObjectivesTo report 52‐week results from a prespecified analysis of patients with active psoriatic arthritis (PsA) having concomitant moderate‐to‐severe plaque psoriasis from the head‐to‐head EXCEED monotherapy study comparing secukinumab with adalimumab.MethodsPatients were randomized to receive secukinumab 300 mg via subcutaneous injection at baseline, week 1–4, and then every 4 weeks until week 48 or adalimumab 40 mg via subcutaneous injection every 2 weeks from baseline until week 50. Assessments in patients with concomitant moderate‐to‐severe psoriasis, defined as having affected body surface area > 10% or Psoriasis Area and Severity Index (PASI) ≥ 10 at baseline, included musculoskeletal, skin and quality‐of‐life outcomes. Missing data were handled using multiple imputation.ResultsOf the 853 patients [secukinumab (N = 426), adalimumab (N = 427)], 211 (24·7%) had concomitant moderate‐to‐severe psoriasis [secukinumab (N = 110, 25·8%), adalimumab (N = 101, 23·7%)]. Up to week 50, 5·5% of patients discontinued secukinumab vs.17·8% in the adalimumab group. The proportion of patients who achieved American College of Rheumatology (ACR) 20 response was 76·4% with secukinumab vs. 68·3% with adalimumab (P = 0·175), PASI 100 response was 39·1% vs. 23·8% (P = 0·013), and simultaneous improvement in ACR 50 and PASI 100 response at week 52 was 28·2% vs. 17·7%, respectively (P = 0·06). Secukinumab demonstrated consistently higher responses vs. adalimumab across skin endpoints.ConclusionsThis prespecified analysis in PsA patients with concomitant moderate‐to‐severe plaque psoriasis in the EXCEED study provides further evidence that IL‐17 inhibitors offer a comprehensive biological treatment to manage the concomitant features of psoriasis and PsA.

Quantifying the rate of recurrence of postoperative Crohn's disease with biological therapy. A meta-analysis.

Preventing the postoperative recurrence (POR) of Crohn's disease (CD) poses a significant challenge to clinicians. With the advent of biologics, various studies have observed a reduction of recurrence after surgery. Hence, we performed a systematic review and meta-analysis to identify the rate of POR at different time points in the era of biologic use. We performed a literature search using Medline and Embase databases for studies investigating biologics in preventing the POR of CD. Data were extracted, and a single-arm meta-analysis with generalized linear mixed model and Clopper-Pearson method for confidence interval (CI) was performed to identify endoscopic, clinical and surgical recurrence rates at 6 months and 1, 2 and 5 years postoperatively. Altogether 24 studies were included in the meta-analysis. The endoscopic, clinical and surgical POR rate with the use of anti-tumor necrosis factor (TNF)-α agents at 1 year was 21.72% (95% CI 16.28%-28.37%), 13.06% (95% CI 8.18%-18.92%) and 3.76% (95% CI 1.37%-9.91%), respectively. The 5-year recurrence rate was 84.21% (95% CI 72.35%-91.57%) and 17.49% (95% CI 9.17%-30.80%) for endoscopic and surgical recurrence, respectively. Subgroup analyses at 1 year for the type of anti-TNF-α agent or the timing of initiation after surgery showed no significant difference in endoscopic, clinical and surgical recurrence rates. Anti-TNF-α agents are effective at preventing clinical, endoscopic and surgical POR of CD. The timing of initiating biological therapy after surgery has no significant effect on the rate of POR. The efficacy of infliximab and adalimumab for postoperative recurrence prevention is similar.

Comparative efficacy of tofacitinib and adalimumab in patients with psoriatic arthritis in real clinical practice. Data from the Russian nationwide register of patients with psoriatic arthritis

Objective: to compare the clinical efficacy in real clinical practice of the targeted synthetic disease-modifying antirheumatic drug (sDMARD) tofacitinib (TOFA) and the biologic DMARD (bDMARD), an inhibitor of tumor necrosis factor alpha (TNFα), adalimumab (ADA) in patients with psoriatic arthritis (PsA), included in the Russian nationwide register of patients with PsA.Patients and methods. The study included 77 patients with PsA (43 men and 34 women) who met the CASPAR criteria and were observed in the Russian nationwide register. Patients were divided into two groups depending on the treatment. Group 1, in which oral TOFA was prescribed, 5 mg 2 times a day, included 41 patients: 24 (58.5%) men and 17 (41.5%) women, the median age was 41 [34; 50] years, the median duration of PsA was 72 [35; 120] months. Group 2, in which subcutaneous ADA was used, 40 mg every 2 weeks, included 36 patients: 19 (52.8%) men and 17 (47.2%) women, the median age was 44 [34; 51] years, the median duration of PsA was 59 [22; 102] months. Combination therapy, including methotrexate (MT), received 80.5% of patients in the TOFA group and 52.8% of patients in the ADA group. At the beginning of the study and every 6 months further, the activity and efficacy of PsA therapy were assessed in all patients according to DAPSA and criteria for minimal disease activity – MDA (number of painful joints ≤1, number of swollen joints ≤1, PASI ≤1 or BSA ≤3 , pain score ≤15, patient's general assessment of disease activity ≤20 mm on a visual analogue scale, HAQ ≤0.5, enthesitis ≤1), dynamics of BASDAI and BSA were also assessed. The number of patients who achieved remission (DAPSA ≤4) or MDA (5 criteria out of 7) during therapy with TOFA and ADA was determined.Results and discussion. Before the start of the therapy in the 1st group, the median DAPSA was 44.2 [37.8; 55.3]: moderate PsA activity was in 5 (12.2%) patients, high in 36 (87.8%) patients. In group 2, the median DAPSA was 35.8 [21.1; 52]: low activity was detected in 3 (8.6%), moderate – in 11 (31.4%), high – in 21 (60%) patients (data from 35 patients was available). 6 months after the start of treatment in patients of the 1st and the 2nd group, there was a significant decrease in all indicators of PsA activity compared to the baseline. The median DAPSA was 11 [4.3; 17.3] and 9.1 [6; 19.6]; remissions according to DAPSA reached 11 (26.8%) and 6 (20.8%) patients, respectively, low activity – 15 (36.6%) and 13 (44.8%), MDA – 16 (40%) and 9 (30%). The number of patients with dactylitis in the 1st and in the 2nd group significantly decreased: from 22 (53.7%) to 5 (13.2%) and from 13 (36.1%) to 6 (20%), respectively. Median HAQ decreased from 1 [0.625; 1.5] to 0.5 [0; 0.875] and from 0.875 [0.5; 1.38] to 0.5 [0; 0.875]; median BASDAI – from 6 [4.2; 7] to 1.4 [0.6; 3.2] and from 4.4 [1.9; 5.8] to 3 [0.8; 4.5], respectively. In group 1, the number of patients with BSA&gt; 3% decreased from 16 (39%) to 8 (26.7%; p&lt;0.225), and in group 2, due to insufficient data (5 patients), we failed to evaluate BSA dynamics.Conclusion. In real clinical practice TOFA and ADA both had comparable efficacy on all clinical manifestations of PsA: after 6 months of therapy, most patients with PsA achieved MDA, low disease activity and remission according to DAPSA and BASDAI.

The Impact of Body Mass Index Upon the Efficacy of Adalimumab in Hidradenitis Suppurativa.

Elevated BMI in Hidradenitis Suppurativa is associated with decreased response to Adalimumab therapy. BMI is proposed to segregate distinct disease subtypes. It remains unresolved whether a threshold BMI exists above which increased dosages may provide clinical benefit. Individual patient data from 578 PIONEER Phase 3 participants were analyzed. Descriptive, multivariable regression analysis and receiver operating characteristic (ROC) curves were calculated to assess the relationship between BMI and clinical outcome measures using R v3.5.3. Participants in the overweight and obese BMI category had reduced odds (58 and 67%, respectively) of achieving HiSCR [OR = 0.42 (95%CI −0.19, 0.91) p = 0.03], [OR = 0.33 (95%CI 0.16, 0.67) p = 0.002] compared to participants with BMI < 25. Reduction in AN count and IHS4 score was not significantly associated. ROC analysis did not reveal any cut off value predictive of treatment outcome. No correlation between BMI and baseline disease activity or covariate interactions were identified. These findings suggest BMI is a significant covariate in the setting of lower baseline disease activity, supporting the concept of disease heterogeneity and differential therapeutic response to Adalimumab.

The Efficacy of Adalimumab as an Initial Treatment in Patients with Behçet’s Retinal Vasculitis

Background: No study has evaluated the effectiveness of Adalimumab (ADA) as first-line in treatment-naïve patients with retinal vasculitis due to Behçet’s Uveitis (BU). Objective: To compare the efficacy of ADA plus conventional therapy and conventional therapy alone as initial treatments in naïve BU patients characterized by retinal vasculitis. Methods: Medical records of BU patients characterized by retinal vasculitis treated with conventional therapy (CT, refers to glucocorticoid and immunosuppressive agents) alone or ADA plus conventional therapy with at least 6 months of follow-up between February 2015 and June 2020 were analyzed. Only patients who were first diagnosed with BU without previous systemic treatment were reviewed. The retinal vasculitis score based on fluorescein angiography (FA), best-corrected visual acuity, glucocorticoid-sparing effect, the number of relapses and ocular complications were evaluated. Results: A total of 45 patients (87 eyes) were included. Twenty-four patients (55.33%) in the CT group were treated with conventional therapy and 21 patients (46.67%) in the ADA group were treated with ADA plus conventional therapy. The inflammatory parameters improved in both groups. FA scores showed significantly greater improvement in ADA group than CT group (p < 0.001). The median number of relapses was significantly lower, and the duration of remission was longer in ADA group than CT group (p < 0.001). At the last visit, a significantly better BCVA improvement (p = 0.024), better inflammation control (anterior chamber inflammation p = 0.017 and vitritis p < 0.001) and lower daily glucocorticoid dosage (p = 0.005) were identified in patients received ADA therapy. In CT group, 1 patient suffered hepatitis B and tuberculosis, 1 had growth retardation, 1 patient had with osteoporosis, then followed by other mild AEs (mostly respiratory upper tract infections); while in ADA group, 1 patient experienced a mild pneumonia (n = 1) while milder AEs were represented mostly by respiratory upper tract infections followed by gastrointestinal discomfort. Conclusion: ADA plus conventional therapy achieved superiority over conventional therapy as initial treatment in naïve BU patients with retinal vasculitis.

Efficacy and safety of adalimumab in paediatric patients with moderate-to-severe ulcerative colitis (ENVISION I): a randomised, controlled, phase 3 study

Biologic treatment options are limited for children with ulcerative colitis. The aim of this study was to assess the safety and efficacy of adalimumab in children with moderate-to-severe ulcerative colitis. The double-blind ENVISION I study was done at 24 hospitals in ten countries. Children (4-17 years) with moderate-to-severe ulcerative colitis despite stable doses of concurrent treatment with oral corticosteroids or immunosuppressants were enrolled. Per the original study design, patients were randomly assigned with an Interactive Voice Response System (IVRS) to receive either high-dose induction adalimumab (2·4 mg/kg [maximum 160 mg] at weeks 0 and 1) or standard-dose induction adalimumab (2·4 mg/kg at week 0 and placebo at week 1); both groups received 1·2 mg/kg (maximum 80 mg) at week 2 and 0·6 mg/kg (maximum 40 mg) at weeks 4 and 6. Patients with partial Mayo score (PMS) response at week 8 (defined as a decrease of two or more points and a decrease of ≥30% from baseline in PMS) were randomly assigned (2:2:1)-using IVRS-to receive either high-dose maintenance adalimumab (0·6 mg/kg weekly), standard-dose maintenance adalimumab (0·6 mg/kg every other week), or placebo up to week 52 (random assignment to the placebo group was ceased mid-trial, as was randomisation in the induction phase with all subsequent patients receiving open-label high-dose induction adalimumab). Coprimary endpoints were the proportion of patients with PMS remission at week 8 (intent-to-treat [ITT]-E population, not including those patients who were not randomised in the induction phase) and full Mayo score (FMS) remission at week 52 in week 8 PMS responders (maintenance ITT-E [mITT-E] population), for which the pooled adalimumab group (patients who received high-dose or standard-dose adalimumab) and the individual dose groups were compared against external adult placebo rates. We report results of the final confirmatory analysis. This trial is registered with ClinicalTrials.gov, NCT02065557. 93 children were recruited between Oct 13, 2014, and Sept 5, 2018, to the main study (77 [83%] were randomly assigned [double-blind] to receive high-dose or standard-dose induction adalimumab; 16 [17%] received open-label high-dose induction adalimumab after study design change). At week 8, 74 (80%) children who were PMS responders continued to the maintenance period. 62 (84%) patients were randomly assigned to receive high-dose or standard-dose maintenance adalimumab treatment; 12 (16%) patients received placebo. In patients in the ITT-E population who were randomly assigned to receive high-dose induction adalimumab, a significantly higher proportion of patients were in PMS remission at week 8 (28 [60%] of 47) compared with external placebo (19·8%; p=0·0001). 13 (43%) of 30 patients in the standard-dose induction adalimumab group were in PMS remission at week 8 versus an external placebo rate of 19·8%, but this difference was not significant (p=0·38). Similarly, FMS remission at week 52 in children who were week 8 PMS responders was reported in a significantly higher proportion of patients in mITT-E population who received high-dose maintenance adalimumab (14 [45%] of 31 patients) versus external placebo at week 52 (18·4%; p=0·0001). Nine (29%) of 31 patients in the standard-dose maintenance adalimumab group were in FMS remission at week 52 versus an external placebo rate of 18·4%, but this difference was not significant (p=0·38). Remission rates in the pooled adalimumab groups were significantly better compared with external placebo (PMS remission at week 8: 41 [53%] of 77 patients; p<0·0001; FMS remission at week 52: 23 [37%] of 62 patients; p=0·0001). 21 (23%) of 93 patients in the main study had one or more treatment-emergent serious adverse events during any adalimumab exposure. The most common adverse events were headache, anaemia, and ulcerative colitis flare during the induction period and ulcerative colitis flare, headache, and nasopharyngitis during the maintenance period. Clinically meaningful rates of remission and response were reported in children who received adalimumab in this study. No new safety signals were observed, suggesting that adalimumab is an efficacious and safe treatment option for children with moderate-to-severe ulcerative colitis. AbbVie.

Complexity of paediatric trials restricts effect on clinical practice

Inflammatory bowel disease (IBD) has become a major burden of health care, with the number of adult and paediatric patients with this chronic disease increasing globally. It has been estimated that there are close to 10 million patients with IBD worldwide. 1 GBD 2017 Inflammatory Bowel Disease CollaboratorsThe global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020; 5: 17-30 Summary Full Text Full Text PDF PubMed Scopus (343) Google Scholar , 2 Ng SC Shi HY Hamidi N et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017; 390: 2769-2778 Summary Full Text Full Text PDF PubMed Scopus (1672) Google Scholar Paediatric IBD is often more severe and extensive compared with adult IBD, and it might restrict growth. Patients with paediatric IBD need glucocorticoids more often than adult patients, and the need of surgery was more frequent in children, in the era before biologics. 3 Turner D Levine A Escher JC et al. Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nut. 2012; 55: 340-361 Crossref PubMed Scopus (279) Google Scholar , 4 Turner D Ruemmele FM Orlanski-Meyer E et al. Management of paediatric ulcerative colitis, part 1: ambulatory care-an evidence-based guideline from European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018; 67: 257-291 Crossref PubMed Scopus (103) Google Scholar , 5 Larsen MD Qvist N Nielsen J et al. Use of anti-TNFalpha agents and time to first-time surgery in paediatric patients with ulcerative colitis and Crohn's disease. J Crohns Colitis. 2016; 10: 650-656 Crossref PubMed Scopus (19) Google Scholar Management of paediatric IBD has shifted towards a more active approach, 3 Turner D Levine A Escher JC et al. Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nut. 2012; 55: 340-361 Crossref PubMed Scopus (279) Google Scholar , 4 Turner D Ruemmele FM Orlanski-Meyer E et al. Management of paediatric ulcerative colitis, part 1: ambulatory care-an evidence-based guideline from European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2018; 67: 257-291 Crossref PubMed Scopus (103) Google Scholar , 6 Ruemmele F Veres G Kolho KL et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease. J Crohns Colitis. 2014; 8: 1179-1207 Summary Full Text Full Text PDF PubMed Scopus (622) Google Scholar , 7 van Rheenen PF Aloi M Assa A et al. The medical management of paediatric crohn's disease: an ECCO-ESPGHAN guideline update. J Crohns Colitis. 2020; (published online Oct 7.)https://doi.org/10.1093/ecco-jcc/jjaa161 PubMed Google Scholar and the use of anti-TNF drugs has increased. Infliximab has been available for paediatric use since 2003, first for Crohn's disease and, since 2011, for ulcerative colitis. The second anti-TNF agent, adalimumab, was only approved by the US Food and Drug Administration in 2021 and European Medicines Agency in 2020 for use in paediatric ulcerative colitis; however, approval for use in Crohn's disease was given in 2014. Why such a delay? The hurdle to getting available drugs licensed for paediatric use is the extreme complexity of drug trials in children. As a result, there are too few paediatric trials, and many children are treated with off-label use of drugs approved for adults. Therefore, the randomised phase 3 trial investigating the use of adalimumab in paediatric ulcerative colitis, by Nicholas Croft and colleagues and published in The Lancet Gastroenterology & Hepatology, 8 Croft NM Faubion Jr, WA Kugathasan S et al. Efficacy and safety of adalimumab in paediatric patients with moderate-to-severe ulcerative colitis (ENVISION I): a randomised, controlled, phase 3 study. Lancet Gastroenterol Hepatol. 2021; (published online June 18.)https://doi.org/10.1016/S2468-1253(21)00142-4 Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar is more than welcome. Efficacy and safety of adalimumab in paediatric patients with moderate-to-severe ulcerative colitis (ENVISION I): a randomised, controlled, phase 3 studyClinically meaningful rates of remission and response were reported in children who received adalimumab in this study. No new safety signals were observed, suggesting that adalimumab is an efficacious and safe treatment option for children with moderate-to-severe ulcerative colitis. Full-Text PDF

Efficacy and safety of adalimumab in hidradenitis suppurativa: A systematic review and meta-analysis of randomized controlled trials.

Background:Adalimumab is used as a first-line biologic agent in the management of moderate-to-severe hidradenitis suppurativa (HS). The objective of the present study was to evaluate the efficacy and safety of adalimumab in patients with moderate-to-severe HS.Methods:We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. Pooled estimates, namely standardized mean difference (SMD) and relative risk (RR), were calculated using random-effect model with trial sequential analysis. Small study effects were examined using the Doi plot. Certainty of evidence (CoE) was assessed using “The Grading of Recommendations Assessment, Development, and Evaluation” approach, and number-needed-to-treat (NNT) was calculated.Results:Five randomized controlled trials, involving 1014 patients, were included. We performed subgroup analysis of adalimumab administered subcutaneously both weekly and every other week. Adalimumab administered weekly was associated with better clinical response achievement (RR 1.76, 95% confidence interval [95% CI] 1.35–2.29; trial sequential analysis TSA-adjusted CI 1.01–3.08; CoE: low; NNT = 5) and a significant improvement in modified Sartorius score (SMD = −0.45, 95% CI = −0.76 to −0.13; CoE: very low; NNT = 10) and dermatology life quality index (DLQI) (SMD −0.47, 95% CI −0.61 to −0.32; CoE: low; NNT = 10). Nevertheless, adalimumab administered every other week showed an improvement only in modified Sartorius score. The pooled RRs of adverse events in both groups revealed no statistical significance when compared with the placebo.Conclusions:Adalimumab administered weekly resulted in not only better clinical responses than placebo but also significantly improved disease severity and quality of life of patients with moderate-to-severe HS. Our study provides supporting evidence to the current guidelines and aids decision-making in the application of adalimumab in HS management.

Update on biologic therapies for juvenile idiopathic arthritis-associated uveitis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, and juvenile idiopathic associated uveitis (JIA-U) is the most frequently noted extra-articular manifestation. JIA-U can present asymptomatically and lead to ocular complications, so regular screening and monitoring are needed to prevent potentially sight-threatening sequelae. Topical glucocorticoids such as prednisolone acetate are usually the first line of treatment for anterior uveitis associated with JIA-U, but long-term use may be associated with cataract, ocular hypertension and glaucoma. Disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate allow tapering of the corticosteroids to prevent long-term complications. Biologic therapies have been increasingly used as targeted therapies for JIA-U, particularly monoclonal antibodies targeting the proinflammatory cytokine TNF-α such as adalimumab and infliximab. One recent, multicenter, prospective, randomized clinical trial provided evidence of the efficacy of adalimumab with methotrexate for JIA-U compared to methotrexate alone. Another clinical trial studying the interleukin-6 inhibitor tocilizumab for JIA-U showed promise in tapering topical corticosteroids. Additionally, JAK inhibitors are emerging biologic therapies for JIA-U in patients refractory to TNF-α inhibitors, with a clinical trial assessing the efficacy of baricitinib for JIA-U underway. While clinical trials on these novel biologics are limited, further investigation of these agents may provide additional therapeutic options for JIA-U.

OP02 Ustekinumab versus adalimumab for induction and maintenance therapy in Moderate-to-Severe Crohn’s Disease: The SEAVUE study

Abstract Background We studied the efficacy and safety of ustekinumab (UST) vs adalimumab (ADA) through 1 year in biologic-naïve patients (pts) with moderate-to-severe Crohn’s disease. Methods SEAVUE was a multicenter, randomized, blinded, parallel-group, active-controlled study in adults with CD Activity Index (CDAI) scores ≥220/≤450. Biologic-naïve pts failing/intolerant to conventional therapy with any size ulcer on baseline (BL) ileocolonoscopy were eligible. Pts were randomized 1:1 to UST (⁓6mg/kg IV at BL then 90mg SC every 8 weeks [Ws]) or ADA (160/80mg SC at BL/W2, then 40mg SC every 2 Ws) per US-approved regimens (no dose modifications). Primary endpoint was clinical remission at W52 (CDAI &amp;lt;150). Major secondary endpoints were corticosteroid-free remission, clinical response (≥100-point CDAI decrease from BL), remission in pt-reported CDAI components (PRO-2 symptom remission: abdominal pain mean daily score ≤1 and stool frequency mean daily score ≤3), and endoscopic remission (SES-CD score ≤3/0 for pts with BL score=3) at W52 and clinical remission at W16. Results 386 pts were randomized to UST or ADA. BL demographics and disease characteristics were balanced between groups and indicative of pts with early, moderate-to-severe CD (median CD duration, 2.58 years; CDAI, 289.5; SES-CD, 8.0). At W52, 65% of UST-treated and 61% of ADA-treated pts achieved clinical remission (Δ=4.0%; 95% CI, -5.5%, 13.5%; p=0.417). Major secondary endpoints, including endoscopic remission, were similar between groups (Table 1), as were remission rates at assessment points through W52. Some other secondary endpoints showed numerical (not statistical) differences between UST and ADA (Table 1). Key safety events are summarized in Table 2. Among UST-treated and ADA-treated pts, 34.0% and 40.5% had infections, 2.6% and 7.2% had serious adverse events (AEs) of worsening CD, and 6.3% and 11.3% had AEs that led to discontinuation (DC) of study drug, respectively. One ADA-treated pt had active pulmonary TB. Injection-site reactions associated with active treatment occurred in 1.0% of UST-treated and 10.3% of ADA-treated pts. Overall, 15.2% of UST-treated and 23.6% of ADA-treated pts DC before W52. Reasons for DC were primarily lack of efficacy (UST, 2.1% vs ADA, 5.1%), AEs (UST, 5.7% vs ADA, 10.7%), and withdrawal of consent (UST, 5.8% vs ADA, 5.1%). Time to treatment DC was longer with UST vs ADA (post hoc analysis). Conclusion Both UST and ADA were highly effective in this population of biologic-naïve pts. Rates of clinical remission at W52 were not statistically significantly different between treatment groups. DC rates were numerically lower for UST. Safety results were consistent with prior experience for both treatments.

P427 Efficacy and safety of vedolizumab and adalimumab in Asian adults with moderately to severely active ulcerative colitis: Post-hoc analysis of the VARSITY trial

Abstract Background The VARSITY trial, the first head-to-head study comparing the efficacy and safety of biologics in patients with moderately to severely active ulcerative colitis (UC), demonstrated superior clinical remission with vedolizumab (VDZ) versus adalimumab (ADA) at week 52. This post-hoc analysis describes outcomes in patients from Asia included in the VARSITY trial. Methods Adult patients with moderately to severely active UC (Mayo score 6–12; endoscopic sub-score ≥2), refractory to conventional therapies and anti–tumour necrosis factor-naïve or -experienced (exposure capped at 25%) were included. This analysis focussed on patients from Hong Kong, Taiwan and South Korea. Patients were randomised (1:1) to receive intravenous (IV) VDZ (300mg) and subcutaneous (SC) placebo on day 1 of weeks 2, 6, 14, 22, 30, 38 and 46 or SC ADA, at weeks 1 (total dose:160mg) and 2 (80mg) and every 2 weeks (40mg) plus IV placebo thereafter until week 50. The primary endpoint was clinical remission at week 52. Secondary endpoints included rates of endoscopic improvement, corticosteroid (CS)-free remission and histological remission at week 52. Patients with missing endpoint assessment at week 52 were considered non-responders. Data were analysed descriptively. Results A total of 45 patients (VDZ: n=21; ADA: n=24) were included. At baseline (VDZ and ADA, respectively), the mostly male population (71.4% and 58.3%) had a mean (SD) age of 46.4 (14.7) and 40.4 (15.1) years; severe disease: 33.3% and 54.2%; mean (SD) disease duration: 6.8 (5.5) and 5.4 (3.5) years; and were biologic-naïve: 85.7% and 79.2%. At week 52, a higher rate of clinical remission was achieved in VDZ- vs. ADA-treated patients (28.6% vs. 16.7%; Table). Adverse events (AEs) occurred in 71.4% (VDZ) and 87.5% (ADA) of patients; serious AEs occurred in 4.8% (VDZ) and 16.7% (ADA) of patients. AEs led to study drug discontinuation in 4.8% (VDZ) and 8.3% (ADA) of patients; no deaths occurred. Conclusion Patients from Asian countries with moderately to severely active UC achieved higher rates of clinical, CS-free, and histological remission as well as endoscopic improvement with VDZ vs. ADA. VDZ and ADA were both generally safe and well tolerated. Descriptive trends were consistent with findings in the larger VARSITY cohort.

P563 Comparison of long-term outcomes of infliximab with adalimumab in biologic naïve patients with Crohn’s disease: a tertiary referral center 13-year experience

Abstract Background The comparative efficacy and safety of infliximab (IFX) and adalimumab (ADA) have shown variable results in biologic-naïve patients with Crohn’s disease (CD). Thus, long-term comparisons between IFX and ADA with or without immunomodulator therapies are still needed. The purpose of this study was to evaluate the long-term clinical effectiveness and safety profile of IFX compared to ADA in biologic-naïve patients with CD. Methods Data of all adult CD patients treated with IFX or ADA as their first biologic agent was collected retrospectively between December 2007 and February 2021. We compared CD-related hospitalization, CD-related major abdominal surgery, steroid use and serious infections leading to treatment cessation. Results Out of 224 biologic-naïve patients with CD, 101 started IFX first (median age at onset: 38.12 years, 61.4% male) and 123 started ADA first (median age at onset: 30.2 years, 64.2% male). Median disease duration was 6.94 years (IQR: 3.82–12.17) and 6.91 years (IQR: 3.94–10.95) for IFX and ADA, respectively, of whom 33% and 37.4% had active smokers, 10.9% and 13.4% had family history of inflammatory bowel disease (IBD) 22.8% and 19.5% had perianal disease, 43.6% and 43.9 had prior major abdominal surgery and 52.6% and 49.6% had extraintestinal manifestations. There were no significant differences between the two groups with respect to the age at onset of tumor necrosis factor antagonist, gender, smoking status, family history of IBD, perianal disease, prior major abdominal surgery, extraintestinal manifestations, prior immunomodulator (Thiopurine or Methotrexate) or steroid usage, all laboratory test results and Crohn’s Disease Activity Index (CDAI) score at baseline (p&amp;gt;0.05). Overall, the median follow-up time was 2.81 and 3.55 years after starting the first IFX and ADA group, respectively. There were no significant differences in the rate of steroid use (4% IFX vs. 10.6% ADA p=0.109), CD-related hospitalization (13.9% IFX vs. 22.8% ADA p=0.127), CD-related major abdominal surgery (9.9% IFX vs. 13% ADA p=0.608) and serious infections leading to treatment cessation (1% IFX vs 0.8% ADA p&amp;gt;0.999) between IFX and ADA. These outcomes were similar in patients treated with IFX or ADA monotherapy or in combination with an immunomodulator. Conclusion In this retrospective observational tertiary referral center study, we observed that there was no significant difference in long-term effectiveness and safety of infliximab and adalimumab in biologic-naïve patients with CD.

POS1044 EFFECT OF SECUKINUMAB VERSUS ADALIMUMAB ON ACR CORE COMPONENTS AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM THE EXCEED STUDY

Background:EXCEED (NCT02745080) was the first fully blinded head-to-head trial to evaluate the efficacy and safety of secukinumab (SEC) versus (vs) adalimumab (ADA) monotherapy in patients with active psoriatic arthritis (PsA) with a primary endpoint of American College of Rheumatology (ACR) 20 at Week 52. Although SEC narrowly missed statistical significance for superiority vs ADA, numerically higher response for other musculoskeletal endpoints and composite indices were observed with SEC.1Objectives:To explore the effect of SEC and ADA on ACR core components, function and Health-related Quality of Life (HRQoL) outcomes.Methods:Patients were randomised 1:1 to receive SEC 300 mg (N=426) subcutaneous (s.c.) at baseline, Week 1-4, followed by every 4 weeks until Week 48 or ADA 40 mg (N=427) s.c. at baseline followed by same dosing every 2 weeks until Week 50. The primary, key secondary and some exploratory endpoints at Week 52 were previously reported.1 A supportive analysis for ACR50 response using logistic regression model and trimmed means model for Health Assessment Questionnaire-Disability Index (HAQ-DI) with gender and smoking status as factors was performed to adjust for imbalances in baseline characteristics. An exploratory analysis of ACR core components with SEC vs ADA at Week 52 was conducted using a mixed-effects repeated measures model that included tender and swollen joint counts, patient and physician global assessment, PsA pain (VAS) and erythrocyte sedimentation rate. HRQoL variables were also exploratory and assessed based on Short Form Health Survey Physical/Mental Component Summary (SF-36 PCS/MCS) scores and Dermatology Life Quality Index (DLQI).Results:The demographic and baseline disease characteristics were comparable across treatment groups, except for an imbalance in sex (females: 51.2% vs 46.4%) and smoking status (yes: 21.8% vs 17.8%) in SEC and ADA group, respectively. At Week 52, ACR50 responses were 49.0% and 44.8% (P=0.0929) and HAQ-DI mean change from baseline were −0.69 and −0.58 (P=0.0314) in SEC and ADA treatment groups, respectively after adjusting for gender and smoking status. No major difference across ACR core components was observed in both treatment groups at Week 52 (Table 1). At Week 52, SEC presented similar improvement in SF-36 PCS/MCS score and numerically higher improvement in DLQI compared to ADA (Figure 1).Conclusion:Secukinumab provided similar improvements in ACR core components and SF-36 based quality of life at Week 52 with adalimumab. Greater improvement in HAQ-DI response and DLQI was demonstrated with secukinumab compared to adalimumab.