Start Of Adalimumab Research Articles

Real-world adalimumab survival and discontinuation factors in hidradenitis suppurativa.

Survival analyses can provide valuable insights into effectiveness and safety as perceived by prescribers. Here, we aimed to evaluate adalimumab (ADA) survival and the interruption risk factors in a multicentre cohort of patients with hidradenitis suppurativa (HS). Moreover, we performed a subanalysis considering the periods before and after the onset of the COVID-19 pandemic. We conducted a retrospective study including 539 adult patients with HS who received ADA from 1 May 2015 to 31 December 2022. Overall drug survival was analysed using Kaplan-Meier survival curves and compared between the subgroups via stratified log-rank test. Possible predictors for overall drug survival and reasons for discontinuation were assessed using univariate and multivariate Cox regression. Overall, 50.1% were females with a mean age of 43.5 ± 1 years and a mean BMI of 29.5 ± 6.7. At the start of ADA, 95.29% were biologic-naïve and 24.63% had undergone surgical treatment. During follow-up, 9.46% of patients required dose escalation, while 39.92% interrupted ADA. Concomitant therapy was used in 64.89% of cases. A subanalyses comparing pre- and post-pandemic periods revealed a tendency to initiate ADA treatment at a younger age, among patient with higher BMI and at a lower HS stage after COVID-19 pandemic. Interestingly, ADA demonstrated extended survival compared to previous studies, with a median overall drug survival of 56.2 months (95% CI 51.2 to 80.3). The primary causes for discontinuation were inefficacy (51.69%), followed by adverse effects (21.35%). Female sex, longer delay in HS diagnosis, higher baseline IHS4 score and concomitant spondyloarthritis were associated with poorer ADA survival or increased risk of discontinuation. ADA demonstrated prolonged survival (median 56.2 months). While addition of antibiotics did not have a positive effect on survival rate, basal IHS4 proved useful in predicting ADA survival.

Efficacy and Safety of Adalimumab in Pediatric Non-infectious Non-anterior Uveitis: Real-life Experience From the International AIDA Network Uveitis Registry.

Scientific evidence of the effectiveness of the tumor necrosis factor inhibitor adalimumab (ADA) in pediatric patients with non-infectious non-anterior uveitis is still limited. The aim of this study is to investigate the therapeutic role of ADA in a cohort of pediatric patients with non-anterior uveitis. This is an international multicenter study analyzing real-life data referred to pediatric patients treated with ADA for intermediate uveitis/pars planitis, posterior uveitis and panuveitis. Data were drawn from the AutoInflammatory Disease Alliance (AIDA) registry for patients with uveitis. Twenty-one patients (36 affected eyes) were enrolled, and all patients benefited from ADA administration. In detail, 11 patients (19 affected eyes) did not experience further ocular inflammation after ADA introduction; 10 cases (17 affected eyes) showed a significant clinical improvement consisting of a decrease in severity and/or frequency of ocular relapses. The number of ocular flares dropped from 3.91 to 1.1 events/patient/year after ADA introduction (p = 0.0009); macular edema and retinal vasculitis were respectively observed in 18 eyes and 20 eyes at the start of ADA and in 4 eyes and 2 eyes at the last assessment. The mean daily glucocorticoid dosage significantly decreased from 26.8 ± 16.8mg/day at the start of ADA to 6.25 ± 6.35mg/day at the last assessment (p = 0.002). Intermediate uveitis/pars planitis (p = 0.01) and posterior uveitis (p = 0.03) were more frequently observed in patients with full response to ADA; panuveitis (p = 0.001) was significantly more frequent among patients continuing to experience uveitic flares. This could be related to a higher use of systemic glucocorticoids (p = 0.002) and conventional immunosuppressants (p = 0.007) at the start of ADA when treating intermediate uveitis/pars planitis. Regarding the safety profile, only one adverse event was reported during ADA treatment, consisting of the development of generalized adenopathy. ADA proved to have an effective therapeutic role in all pediatric patients with non-anterior uveitis enrolled in the study. An overall glucocorticoid-sparing effect was observed despite the severity of cases enrolled. A more aggressive treatment of panuveitis and posterior uveitis at start of ADA could increase the likelihood of full response to therapy.

Adalimumab Therapy in Pediatric Crohn Disease: A 2-Year Follow-Up Comparing "Top-Down" and "Step-Up" Strategies.

European Crohn's Colitis Organization (ECCO) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines recommend the early use of anti-tumor necrosis factor (TNF) biologicals in pediatric Crohn disease (CD) patients with positive predictors for poor outcome. The objective of the present study was to compare early "Top-Down" use of adalimumab (ADA) immunomodulator/biologics-naive patients to conventional "Step-Up" management. One hundred and twenty consecutive patients with a confirmed diagnosis of CD and treated with ADA between 2008 and 2019 were included and allocated to the ADA-Top Down (n = 59) or ADA-Step Up group (n = 61). The primary endpoint was prolonged steroid-/enteral nutrition-free clinical remission at 24 months, defined by a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) < 12.5. Clinical and biological data were collected at 12 and 24 months. At start of ADA, disease activity was comparable between the ADA-Top Down group and the ADA-Step Up group (wPCDAI = 31 ± 16 vs 31.3 ± 15.2, respectively, P = 0.84). At 24 months, the remission rate was significantly higher in the ADA-Top Down group (73% vs 51%, P < 0.01). After propensity score, the Top-Down strategy is still more effective than the Step-Up strategy in maintaining remission at 24 months [hazard ratio (HR) = 0.36, 95% CI (0.15-0.87), P = 0.02]. Patients in the ADA-Top Down group were mainly on monotherapy compared to patients in the ADA-Step Up group (53/55 vs 28/55 respectively, P < 0.001). Serum levels of ADA were higher in the ADA-Top Down group than in the ADA-Step Up group (12.8 ± 4.3 vs 10.4 ± 3.9 µg/mL, respectively, P < 0.01). There were no serious adverse events. Early use of ADA appears to be more effective in maintaining relapse-free remission at 2 years, while using it as monotherapy. These findings further favor the recommendation of early anti-TNF use in high-risk CD patients.

Analysis of Therapeutic Response to Adalimumab in Behçet’s Uveitis by Ultra-Widefield Fluorescein Angiography

Purpose: To investigate the role of ultra-widefield fluorescein angiography (UWFA) for monitoring the therapeutic response to adalimumab in patients with Behcet’s uveitis.Methods: Patients with Behcet’s uveitis treated with adalimumab for ≥ 30 weeks were included. The best-corrected visual acuity (BCVA), grading of anterior chamber cell, grading of vitreous haze, and UWFA findings were assessed at baseline, and at 6, 14, and 30 weeks from the start of adalimumab treatment.Results: A total of 32 eyes of 17 patients were included. There were significant decreases in BCVA and UWFA scores at 6, 14, and 30 weeks after adalimumab administration. UWFA scores for vascular and capillary leakage were decreased at 30 weeks (&lt;i&gt;p&lt;/i&gt; = 0.032, &lt;i&gt;p&lt;/i&gt; = 0.004), while the UWFA scores for disc hyperfluorescence persisted (&lt;i&gt;p&lt;/i&gt; = 0.083). Although vascular and capillary leakage at the posterior pole was significantly decreased at 6, 14, and 30 weeks, there was no significant change of the score for peripheral vascular and capillary leakage from baseline to 6 weeks, from 6 to 14 weeks, and from 14 to 30 weeks.Conclusions: UWFA can be used to evaluate the treatment response of adalimumab in Behcet’s uveitis. The vascular leakage pattern varies depending on the location of retinal vessels.

Adalimumab versus azathioprine to halt the progression of bowel damage in Crohn’s disease: application of Lémann Index

Background: The Lémann Index (LI) was recently developed to evaluate the cumulative bowel damage in patients with Crohn’s disease (CD).Aims: To search for a difference between adalimumab and azathioprine to halt the progression of bowel damage in active CD, using the LI.Methods: A single-centre, retrospective study was conducted. Patients with CD were included if they had colonoscopy and magnetic resonance enterography performed within 4 months from the start of adalimumab or azathioprine and repeated after 12 months of therapy. Primary outcome was reached if the increase of LI after 12 months of treatment was <0.3, the drug was not stopped, and the use of systemic steroids was continued for no more than 3 months.Results: Ninety-one patients were enrolled, 31 (34.1%) of them treated with adalimumab and 60 (65.9%) with azathioprine. Sixty-seven percent of patients treated with adalimumab reached the primary outcome compared to 28.3% of patients treated with azathioprine (p = .0006). The LI in the group on adalimumab therapy decreased after 12 months (from 9.9 to 8.8), while in the group on azathioprine therapy it increased (from 7.7 to 8.8).Conclusion: Treatment with adalimumab halts the progression of bowel damage in CD while that with azathioprine does not.

Proactive Therapeutic Drug Monitoring of Adalimumab Is Associated With Better Long-term Outcomes Compared With Standard of Care in Patients With Inflammatory Bowel Disease.

Therapeutic drug monitoring [TDM] has proven to be effective for optimising anti-tumour necrosis factor [TNF] therapy in inflammatory bowel disease [IBD]. Nevertheless, the majority of data refer to infliximab and reactive testing or association studies. We aimed to compare the long-term outcome of patients with IBD who received at least one proactive TDM of adalimumab, with standard of care, defined as empirical dose escalation and/or reactive TDM. This was a multicentre retrospective cohort study. Patients on maintenance adalimumab therapy from June 2006 to December 2015 were eligible. We analysed time to treatment failure from start of adalimumab until the end of follow-up [July 2016]. Treatment failure was defined as drug discontinuation for secondary loss of response or serious adverse event or need for IBD-related surgery. Serum adalimumab concentrations and antibodies to adalimumab were measured using the Prometheus homogeneous mobility shift assay. A total of 382 patients with IBD [Crohn's disease, n = 311, 81%] were included and received either at least one proactive TDM [n = 53] or standard of care [empirical dose escalation, n = 279; reactive TDM, n = 50]. Patients were followed for a median of 3.1 years [interquartile range, 1.4-4.8 years]. Multiple Cox regression analyses showed that at least one proactive TDM was independently associated with a reduced risk for treatment failure (hazard ratio [HR]: 0.4; 95% confidence interval [CI]: 0.2-0.9; p = 0.022). This multicentre, retrospective cohort study reflecting real-life clinical practice provides the first evidence that proactive TDM of adalimumab may be associated with a lower risk of treatment failure compared with standard of care in patients with IBD.

PTU-069 Effect of Adalimumab on Patients with Moderate to Severe Ulcerative Colitis in UK Clinical Practice Setting: Results from Inspirada

Introduction Limited real world data are available regarding the effects of adalimumab (ADA) on UK patients with moderate to severe ulcerative colitis (UC). Methods INSPIRADA was a single-arm, multi-country, open-label study that evaluated the effect of ADA on patients with UC treated according to usual clinical practice. Adults with active moderate to severe UC who failed immunosuppressive therapies and experienced rectal bleeding within 7 days of baseline (BL) were enrolled. Prior use of anti-TNF was allowed. Clinical outcomes included Simple Clinical Colitis Activity Index (SCCAI) response (a decrease ≥2 points compared to BL) and remission (SCCAI ≤2). HRQoL (EQ-5D-5L and SIBDQ), treatment satisfaction with medication (TSQM), and work productivity and activity impairment (WPAI) were measured from BL to week 26. Direct medical costs (excluding ADA costs) were estimated using 2014 UK National Health Service reference costs. Indirect costs were based on the WPAI using average weekly earnings from the 2014 UK Annual Salary Survey of Hours and Earnings. Change (defined as 6 mo after start of ADA vs 6 mo before) in resource use and costs were calculated. Data for the intent-to-treat population in UK were analysed. Missing data were imputed using last observation carried forward. Results Data from 90 UK patients (58% male, mean age 39 yrs) were analysed. Mean SCCAI at BL was 8.2. At week 2, 74% achieved SCCAI response and 21% achieved SCCAI remission. At week 8, 73% achieved SCCAI response, 40% in remission and 49% had no blood in stool. At week 26, 66% achieved SCCAI response, 42% in remission and 51% had no blood in stool. Significant improvements, as early as within 2 weeks, in SIBDQ (19.5 points, p Conclusion Real world rates of response, remission and improvements in HRQoL with ADA for UK patients with moderate to severe UC were clinically meaningful. ADA improved work productivity, increased patient satisfaction with therapy and reduced health care associated costs for these patients in the UK. Disclosure of Interest P. Irving Grant/research support from: AbbVie; Falk; Ferring; Genentech/Roche; Hospira; Merck; Pharmacosmos; Shire; Takeda; Tillotts; Topivert; Vifor and Warner Chilcott, Conflict with: Advisor/invited lecturer for: AbbVie; Falk; Ferring; Genentech/Roche; Hospira; Merck; Pharmacosmos; Shire; Takeda; Tillotts; Topivert; Vifor and Warner Chilcott, F. Cummings Conflict with: Advisor/lectures for: Takeda, Abbvie, MSD, Biogen, Napp, Hospira, Janssen, S. Bloom Conflict with: Advisor/lectures for: Takeda, Tillotts, Abbvie, MSD, Pharmacosmos, Vifor, Johnson and Johnson, A. Lazar Shareholder of: AbbVie, Employee of: AbbVie, A. Robinson Shareholder of: AbbVie, Employee of: AbbVie, B. Pappalardo Shareholder of: AbbVie, Employee of: AbbVie, M. Bereswill Shareholder of: AbbVie, Employee of: AbbVie, M. Skup Shareholder of: AbbVie, Employee of: AbbVie, N. Chen Shareholder of: AbbVie, Employee of: AbbVie, T. Finney-Hayward Shareholder of: AbbVie, Employee of: AbbVie, S. Wang Shareholder of: AbbVie, Employee of: AbbVie, R. Thakkar Shareholder of: AbbVie, Employee of: AbbVie, S. Travis Grant/research support from: AbbVie; Asahi; Boehringer Ingelheim; BMS; Cosmo; Elan; Ferring; FPRT Bio; Genentech/Roche; Genzyme; Glenmark; GW Pharmaceuticals; Lilly; Merck; Novartis; Novo Nordisk; Ocera; Pfizer; Shire; Santarus; SigmoidPharma; Synthon; Takeda; Tillotts; Topivert; Trino Therapeutics with Wellcome Trust; UCB Pharma; Vertex; VHsquared; Vifor; Warner Chilcott and Zeria, Conflict with: Advisor or paid instructor for: AbbVie; Asahi; Boehringer Ingelheim; BMS; Cosmo; Elan; Ferring; FPRT Bio; Genentech/Roche; Genzyme; Glenmark; GW Pharmaceuticals; Lilly; Merck; Novartis; Novo Nordisk; Ocera; Pfizer; Shire; Santarus; SigmoidPharma; Synthon; Takeda; Tillotts; Topivert; Trino Therapeutics with Wellcome Trust; UCB Pharma; Vertex; VHsquared; Vifor; Warner Chilcott and Zeria. All advisory boards were suspended Q1 2012–14 while President of ECCO

Growth and bone health in paediatric patients with Crohn's disease receiving subcutaneous tumor necrosis factor antibody.

To study whether adalimumab (ADA) was associated with improvement in growth, bone mineral density (BMD) and bone metabolism. In children with Crohn's disease (CD) there is a high prevalence of growth failure and reduced BMD. Treatment with infliximab is associated with an improvement in growth. Anthropometry, paediatric CD activity index (PCDAI), bone markers and BMD was measured in 18 patients (72% females) one year before and after start of ADA with a median age of 14.4 years (range: 5-19 years) at treatment start. Outcomes were indicators of growth with treatment as well as interval growth. Eleven (61%) children experienced catch-up growth after ADA. PCDAI significantly decreased from 52.1 ± 16 to 30.4 ± 23 (P ≤ 0.001). Post ADA, body mass index (BMI) standard deviation score (SDS) 0.1[range: 2.7-(-0.8)] vs -1 [range: 0.1-(-3.6)], P = 0.04 and ∆BMI SDS in children 0.3 [range: 0.7-(-0.2)] vs -1.1 [range: 1.2-(-2.3)], P = 0.01 in remission were significantly higher compared to those with moderate to severe inflammation. The main predictors for growth were 25-hydroxycholecalciferol and for bone mineralisation weight and height SDS. ADA had no significant influence on bone markers and BMD. Next to improvement of PCDAI, half of the children achieved a positive catch-up growth. A better nutritional status with improvement in BMI and weight is positive predictor for improved growth and bone mineralisation.

O-30: Long-term efficacy of adalimumab in paediatric patients with Crohn’s disease

O-30: Long-term efficacy of adalimumab in paediatric patients with Crohn’s disease

Adalimumab therapy for psoriasis in real‐world practice: efficacy, safety and results in biologic‐naïve vs. non‐naïve patients

Patients and the course of treatment in daily practice are different from randomized controlled trials (RCTs). to analyse the percentage of patients achieving PASI 75. PASI 50, PASI 90, PASI 100 responses, the percentage of patients experiencing at least one serious adverse event (SAE) and the response in biologic-naïve vs. non-naïve patients. Prospectively collected efficacy and safety data of a cohort of psoriasis patients treated with adalimumab in daily practice between May 2007 and July 2011 were analyzed. Efficacy was determined using an intention-to-treat analysis and an as treated analysis, in comparison with the course baseline PASI before the start of adalimumab and the original baseline PASI before the start of any biologic therapy. Eighty-five patients received adalimumab therapy with a mean treatment duration of 1.4 (range 0.02-3.1) years. Compared with the original baseline PASI, PASI 75 response rates at week 12 and 24 were 34% and 38% (ITT). PASI 75 responses were well maintained until week 132. Only the PASI 75 response rate at week 12 differed significantly between biologic-naïve (56%) and non-naïve patients (29%). Sixteen patients (19%) experienced 28 SAEs. Seven patients (8%) experienced SAEs considered possibly or probably related to adalimumab. In this cohort, PASI75 responses were substantial but lower than in RCTs and other daily practice studies. Efficacy was well maintained during more than 2 years of follow-up and differed only between biologic-naïve and non-naïve patients at week 12. The incidence of SAEs was low but seems higher than observed in RCTs.

Commentary: BMI and the need for adalimumab dose escalation in Crohn's disease – authors’ reply

We would like to clarify some of the questions raised by Van Assche et al.1 in response to our recently published article.2 We believe indeed that a real pharmacokinetic analysis is valuable to exclude confounders and is warranted in further research on this topic. However, our study was directed towards predictive factors before the start of adalimumab, and therefore anti-TNF levels were not included. Furthermore, we would like to note that patients stopped due to adverse events (21, 29%), loss of response (37, 51%), patients’ preferences (13, 18%), or unknown reasons (2, 3%), and no primary nonresponders were included. Of the patients who had dose escalation and were previously exposed to infliximab, 12 regained response 3 months after dose escalation, follow-up data were not available for three patients and in 12 patients, dose escalation was not effective. We agree with Van Assche et al. that further research is warranted. Declaration of personal interests: None. Declaration of funding interests: C. Janneke van der Woude has served as a speaker, a consultant and an advisory board member for MSD, Falk, Abbott and Shire, and has received research funding from Falk and Ferring.

Switching from a first to a second tumour necrosis factor (TNF) alpha antagonist in patients with juvenile idiopathic arthritis

Results A total of 33 patients initially treated with Etanercept were switched to Adalimumab after a mean of 25.9 months (range 3–87 months). Reasons for discontinuation of Etanercept were inefficacy (n = 23, 65.8%), uveitis (n = 6, 17.1%), intolerance (n = 3, 8.6%) and patients' request (n = 6, 17.1%). Follow up data on Adalimumab were obtained from 12 patients for a range of 2 to 26 months (mean 10.9 months). The maximum response rate of the PedACR30/50/70 on Etanercept was 82.4%/73.5%/ 67.6%. The last documented response rate on Etanercept showed a decrease to 47.1%/35.3%/29.4% (PedACR30/ 50/70). After switching to Adalimumab a maximum PedACR30/50/70 of 75%/66.7%/50% compared to start of Etanercept and 33.3/33.3/25 compared to start of Adalimumab was reached. Treatment on both drugs was safe with no report of serious AE. Conclusion Although a number of patients have reached a good PedACR response rate on Etanercept, treatment was unsatisfied and therefore it was switched to Adalimumab. According to the PedACR only minor improvement was observed after switching to Adalimumab. from 15th Paediatric Rheumatology European Society (PreS) Congress London, UK. 14–17 September 2008