Discontinuation Of Adalimumab Research Articles

#2475 Glomerulonephritis associated with anti -TNF-α therapy

Abstract Background and Aims Biologic agents like tumor necrosis factor α inhibitors/ anti-TNF-α/, IL6 and CD80/26 are widely used in many rheumatologic diseases but these may also elicit effects on renal function. These drugs, as well as rheumatic diseases themselves, can cause autoimmune renal disorders. Though effective on the main inflammatory process the incidence of kidney injury associated with their administration is increasing. Various forms of glomerulopathies have been described in connection with biological therapy - proliferative lupus nephritis, oligo immune necrotizing crescentic glomerulonephritis, membranous glomerulonephritis, IgA nephropathy and others. Method We report the clinical and pathologic findings in two patients with Rheumatoid arthritis and Ankylosing spondylitis on biologic therapy with an anti-TNF-α agent. During the treatment they presented with nephritic syndrome requiring kidney histology. Results Case 1: The first patient is a 52-year-old man diagnosed with ankylosing spondylitis, HLA-B27 positive, 15 years before admission. Four years before admission treatment with Golimumab /anti-TNF-α/ has been initiated. During the follow-up period urine tests revealed proteinuria and hematuria, which required more detailed tests. The patient presented with clinical features of nephritic syndrome, marked lower extremity edema, hematuria, nephrotic range proteinuria, impaired hypertension control. Kidney biopsy revealed membranoproliferative glomerulonephritis. It was assumed that kidney injury was most likely associated with Golimumab therapy. Its administration was discontinued, and therapy was started with pulses of Methylprednisolone 500 mg i.v. in three consecutive days, Cyclophosphamide 500 mg i.v., repeated the second and third month, followed by low steroid doses 0,5 mg/kg with gradual tapering. Mycophenolate Mofetil 1500 mg was started from the third month. General condition and laboratory results improved considerably. The occurrence of stiffness and pain in the sacroiliac joints several months after stopping biologic treatment necessitated the inclusion of Sulfasalazine to the therapy. Initiation of therapy with another class of biologic agent, Anti-IL-17 monoclonal antibody, was discussed with the follow-up rheumatologists. Case 2: The second patient is a 66-year-old woman, with a history of hypertension and essential thrombocythemia, who was diagnosed with seropositive rheumatoid arthritis 3 years before admission, treated with Adalimumab /anti-TNF-α/. Follow-up examinations revealed low-grade proteinuria, hematuria and impaired renal function. Kidney biopsy revealed IgA nephropathy. Following the discontinuation of Adalimumab, the patient was treated with pulses of Methylprednisolone 500 mg i.v. in three consecutive days, Cyclophosphamide 500 mg i.v., repeated the second and third month, followed by low steroid doses 0,5 mg/kg with gradual tapering. Kidney function significantly improved at the third month of treatment and proteinuria was gradually reduced. Initiation of Rituximab /antiCD20/ treatment was discussed with rheumatologists. Conclusion Treatment with biological drugs can cause immune-mediated glomerular disorder/IGD/. These events are rare, and the causative effects of a specific drug is hard to establish. When a patient is suspected of having an IGD, kidney biopsy should be performed for the exact diagnosis. The drug should be discontinued, and the treatment for the new-onset renal disorder should be promptly started. A rechallenge test of the same or a similar drug should be avoided, whereas switching to a different therapy is a reasonable option.

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.

P870 Effectiveness and safety of adalimumab as first line biological treatment in Ulcerative Colitis

Abstract Background The increase in licensed therapies for ulcerative colitis (UC) is revolutionizing its treatment but making first line choice more challenging. Adalimumab (ADA) is inexpensive but, anecdotally, is sometimes regarded as less effective than other first line advanced therapies. We aimed to evaluate the results of first line ADA in UC. Methods We performed a single centre retrospective analysis of UC patients started on ADA between January 15 and March 2022 in an IBD referral hospital. Clinical remission was defined as SCCAI <2 points, endoscopic remission as a UCEIS <2 points and treatment failure as the need for colectomy or second biological line Results A total of 79 patients were included (Table 1). Median follow-up was 19 months (2-91); 78.5% were followed >6 months. At 6 months, 80.3% (61/76) and 37.3% (22/59) of the patients were in clinical and endoscopic remission, respectively. 54.3% received combination treatment with immunomodulators (50.6% thiopurines, 3.7% methotrexate). Dose intensification to weekly treatment occurred in 27.8% after median 9 months (4-48 months). During follow-up 51% received corticosteroids at some point (26% topically-acting oral corticosteroids, 10% oral corticosteroids, 15% both). Of patients who received steroids, 55% (22/40) were able to continue adalimumab therapy. 2.5% of patients were hospitalised for a disease flare. 5.1% had an infection recorded during follow up, none discontinued the treatment. No other major adverse events were recorded. In 22.8% (18/79) of patients, ADA was stopped due to treatment failure, mean 15 months after starting the drug (4-56 months), (Figure 1). None of these patients underwent colectomy at the time of stopping the drug; in 17/18 a second biological therapy was started (10 tofacitinib, 1 filgotinib, 1 upadacitinib, 2 ustekinumab, 2 vedolizumab, 1 golimumab). TDM was performed using a drug-sensitive ELISA, which is only able to detect antidrug antibodies when drug levels are low or absent. Drug levels at the time of stopping the drug were <5 µg/mL in 22% of patients (in 2 antibodies were detected), 5-8 µg/mL in 11% and >8 µg/mL in 67%. Conclusion In a real-world UC cohort, ADA appears to be an effective well tolerated first-line advanced therapy with the vast majority of patients reaching clinical remission and a significant proportion achieving mucosal healing. Table 1. Cohort characteristics (N 79, frequency and %). Figure 1: Kaplan-Meier survival analysis of time to ADA discontinuation.

Analysis of duration of remission of psoriasis after discontinuation of targeted therapy: Search for predictors of early relapse of disease

Purpose of the study. To establish patterns of changes in the duration of the remission period in patients suffering from severe psoriasis after discontinuation of targeted therapy.Materials and methods. The work was carried out in the design of an open randomized interventional prospective study and was carried out in two successive stages. To calculate indicators of the expected duration of the remission period, Kaplan – Meier ‘survival’ analysis was used with the construction of ‘survival’ tables and curves assessing the significance of differences using the Mantel – Cox log-rank test. Significant factors presumably influencing the increase in the cumulative risk of relapse were determined by multivariate Cox regression.Results. The longest period of remission was typical for patients who were prescribed systemic therapy with guselkumab – 33.5 weeks, the second longest period of remission was ustekinumab – 29.1 weeks, the third – secukinumab – 24.7 weeks. The average duration of remission after discontinuation of adalimumab used for a year was 17.4 weeks. The worst disease-free period was recorded for apremilast – 6.9 weeks (p < 0.001 for all comparisons). Significant predictors of early onset of psoriasis relapse were the following factors: the presence of a family history, failure to achieve the PASI 75 indicator by the 16th week of treatment, delayed prescription of targeted therapy (more than 3 years after the diagnosis of ‘severe psoriasis vulgaris’), high values of the PASI index at the time of initiation of systemic therapy and long duration of illness.Conclusions. Resumption of systemic treatment was required in 25.8 %, 35.3 %, and 12.1 % of patients within the first 6 months after discontinuation of ustekinumab, secukinumab, and guselkumab, respectively. When patients received adalimumab, re-prescription of targeted therapy was required in 33.3 % of cases 4 months after discontinuation, and when prescribed apremilast – in 64.5 % of cases already 2 months after discontinuation. Among all systemic drugs examined, the IL‑23 inhibitor (guselkumab) was associated with the longest period of psoriasis remission after discontinuation of targeted treatment. The identified predictors of early disease relapse indicate the importance of personalized targeted therapy and open up the possibility of prognostic assessment of the expected duration of the disease-free period after discontinuation of systemic treatment.

BI22 Successful treatment of antitumour necrosis factor-α-induced paradoxical palmoplantar pustulosis with tofacitinib

Abstract Palmoplantar pustulosis (PPP) is an inflammatory skin condition characterized by eruptions of sterile pustules on the palms and/or soles. These eruptions cause significant discomfort and have a major impact on a patient’s quality of life. The exact cause of PPP remains unknown; several theories have been hypothesized. These theories include genetic factors, including mutations in IL36RN, associations with autoimmune/autoinflammatory disorders and drug-induced aetiologies. Tumour necrosis factor (TNF)-α inhibitors are widely used in the treatment of autoimmune conditions such as psoriasis, psoriatic arthritis, rheumatoid arthritis and inflammatory bowel disease. An unusual side-effect of these treatments is their ability to induce paradoxical reactions. It is reported in the literature that this can occur in 2–5% of patients receiving TNF-α inhibition. We report a case of anti-TNF-α-induced paradoxical PPP in a 52-year-old woman with rheumatoid arthritis (RA). Three months after commencing adalimumab for her RA, the patient developed painful sterile pustules on her palms and soles. She was a smoker with no previous history of psoriasis. Her adalimumab treatment was discontinued, and her hands and feet were treated with clobetasol propionate. Despite 3 months of topical treatment and discontinuation of adalimumab, her PPP deteriorated. Interleukin (IL)-17 or IL-23 inhibition was considered but is not indicated for the treatment of RA. To gain control of both her RA and PPP, she was started on tofacitinib 5 mg twice daily, a partial and reversible JAK1 and JAK3 inhibitor. Within 4 days, the pustulosis on her hands and feet improved, and within 3 months, she had total disease clearance with a complete response. Her Dermatology Life Quality Index improved from 23/30 to 0/30. The patient developed a dental abscess on treatment. During this infection, her tofacitinib was withheld for 2 weeks and was treated with metronidazole. During this period, she had an acute flare of her PPP, which quickly resolved once recommencing tofacitinib. In a recent systematic review, a total of 155 patients with biologic-associated paradoxical PPP were identified, with the most common cause being TNF-α inhibition, with female sex, smoking and concomitant autoimmune disorders being major risk factors. To date, only five case reports have described the successful treatment of PPP with tofacitinib. We found that tofacitinib is an effective and rapid treatment for paradoxical PPP.

Vogt-Koyanagi-Harada-like Syndrome Induced by Checkpoint Inhibitor Cemiplimab.

Checkpoint inhibition targeting programmed cell-death protein 1 has demonstrated efficacy for a wide range of indications including cutaneous malignancy. However, immune-related adverse events (irAEs), including infrequent but visually impactful ocular irAEs, require careful consideration of treatment options, including medication withdrawal, local corticosteroids, or rarely immunomodulation. This case presents a 53-year-old woman who developed uveitis and mucous membrane ulcers after treatment for numerous cutaneous neoplasms, primarily squamous cell carcinoma, with the programmed cell-death protein 1 inhibitor cemiplimab. Ophthalmic examination revealed diffuse choroidal depigmentation consistent with a Vogt-Koyanagi-Harada-like syndrome. Topical and periocular steroids were used to treat the intraocular inflammation, and cemiplimab was discontinued. Because of ongoing severe uveitis, systemic corticosteroids and corticosteroid-sparing immunosuppression were initiated. Specifically, azathioprine and methotrexate were introduced, but each was stopped due to side effects, prompting the initiation of adalimumab (ADA) treatment. While ADA controlled intraocular inflammation, the squamous cell carcinomas were noted to progress, resulting in the discontinuation of ADA. However, a uveitis recurrence was observed. After a discussion of risks and benefits of biologic immunosuppressive therapy, including the risk of vision loss, ADA was restarted with successful disease quiescence at a 16-month follow-up. The cutaneous neoplasms were managed with topical and intralesional therapies, such as 5-fluorouracil. Recent dermatologic examinations suggested no new cutaneous lesions. This scenario presents the effective use of ADA in an ocular irAE that balances the management of sight-threatening ocular inflammation with the risk of promoting recurrent or de novo neoplastic disease.

Real-world outcomes of switching from adalimumab originator to adalimumab biosimilar in patients with inflammatory bowel disease: The ADA-SWITCH study.

Data on the outcomes after switching from adalimumab (ADA) originator to ADA biosimilar are limited. The aim was to compare the treatment persistence, clinical efficacy, and safety outcomes in inflammatory bowel disease patients who maintained ADA originator vs. those who switched to ADA biosimilar. Patients receiving ADA originator who were in clinical remission at standard dose of ADA originator were included. Patients who maintained ADA originator formed the non-switch cohort (NSC), and those who switched to different ADA biosimilars constituted the switch cohort (SC). Clinical remission was defined as a Harvey-Bradshaw index ≤4 in Crohn's disease and a partial Mayo score ≤2 in ulcerative colitis. To control possible confounding effects on treatment discontinuation, an inverse probability treatment weighted proportional hazard Cox regression was performed. Five hundred and twenty-four patients were included: 211 in the SC and 313 in the NSC. The median follow-up was 13 months in the SC and 24 months in the NSC (p < 0.001). The incidence rate of ADA discontinuation was 8% and 7% per patient-year in the SC and in the NSC, respectively (p > 0.05). In the multivariate analysis, switching from ADA originator to ADA biosimilar was not associated with therapy discontinuation. The incidence rate of relapse was 8% per patient-year in the SC and 6% per patient-year in the NSC (p > 0.05). Six percent of the patients had adverse events in the SC vs. 5% in the NSC (p > 0.05). Switching to ADA biosimilar did not impair patients' outcomes in comparison with maintaining on the originator.

Drug utilization of biologic therapy in Crohn’s disease and ulcerative colitis: a population-based Danish cohort study 2015–2020

Objective The aim of the study was to characterize the drug utilization and switch patterns of biological treatment of ulcerative colitis (UC) and Crohn’s disease (CD). Methods Using Danish national registries, this nationwide study included individuals diagnosed with UC or CD, bio-naïve at the initiation of treatment with infliximab, adalimumab, vedolizumab, golimumab, or ustekinumab in 2015–2020. Hazard ratios of discontinuing the first treatment or switching to another biological treatment were explored using Cox regression. Results Among 2995 UC patients and 3028 CD patients, infliximab was used as a first-line biologic treatment in 89% of UC patients and 85% of CD patients, followed by adalimumab with 6%, vedolizumab with 3%, and golimumab with 1% for UC, and adalimumab with 12%, vedolizumab with 2%, and ustekinumab with 0.4% for CD. When comparing adalimumab as the first treatment series to infliximab, there was a higher risk of treatment discontinuation (excluding switch) among UC patients (hazard ratio: 2.02 [95% confidence interval: 1.57; 2.60]) and CD patients (1.85 [1.52; 2.24]). When comparing vedolizumab to infliximab, there was a lower risk of discontinuation for UC patients (0.51 [0.29–0.89]), and for CD patients, although not significantly (0.58 [0.32–1.03]). We observed no significant difference in the risk of switching to another biologic treatment for any of the biologics. Conclusion More than 85% of UC and CD patients initiating biologic therapy had infliximab as their first-line biologic treatment, in accordance with official treatment guidelines. Future studies should explore the higher incidence of treatment discontinuation of adalimumab as the first treatment series. Key summary Several biologic therapies are available in the treatment of ulcerative colitis and Crohn’s disease. Clinical guidelines stipulate that infliximab should be the first-line biologic therapy. Drug utilization studies comparing biologic therapies head-to-head are sparse. In Denmark, during 2015–2020 infliximab remained the most widely used biologic treatment, with adalimumab being second. One in four patients experienced more than one biologic during the study period. The risk of discontinuation of biologic treatment (and not starting a new biologic) was higher for initiators of adalimumab. Clinical and social background factors available from the registers could not account for the observed risk difference in discontinuation.

POS1322 DISCONTINUATION OF LONG-TERM ADALIMUMAB TREATMENT IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS-ASSOCIATED UVEITIS

BackgroundUveitis is the most common extra-articular manifestation of JIA which may lead to sight-threatening ocular complications. Topical corticosteroids are still used in the initial treatment for JIA-associated uveitis. The goal of treatment in these patients should be topical corticosteroid-free remission and prevention of recurrences. The most commonly used corticosteroid-sparing immunomodulatory are TNF-α inhibitors (TNFi), especially adalimumab.Currently, limited data are available about when or how to stop adalimumab when remission of JIA-associated uveitis is presumed.ObjectivesTo evaluate rates of relapse after discontinuation adalimumab in patients with JIA-associated uveitis.MethodsMedical records of 33 patients with JIA-associated uveitis who were successfully treated with adalimumab to a state of topical corticosteroid-free remission and discontinued adalimumab due to a long-term remission were analyzed retrospectively.Remission of uveitis was defined as &lt;1+ cells in the anterior chamber and &lt;1 + vitreous haze grading; relapse was defined as ≥1 cell in the anterior chamber or ≥1 vitreous haze grading [1].ResultsCorticosteroid-sparing control of inflammation was achieved in all patients. Adalimumab was discontinued after 50 (range 12–120) months after initiation of adalimumab. Duration of remission prior to discontinuing adalimumab was 42 (range 6 – 114) months. The mean duration of remission after adalimumab discontinuation was 14 (range 1–59) months. 13 (40%) of patients had flares after less than 12 months after discontinuing adalimumab, 5 (15%) had flares after 12 – 24 months, 15 (45%) had not flared due to 24 months after discontinuation adalimumab and had had a long-term non-biological remission. Disease was successfully controlled in 11(33%) patients with non-biological DMARDs, 22 (66%) patients restarted biological therapy after flares, due to lack of improvement after non-biological DMARDs. All patients in whom biological therapy was reinitiated responded satisfactorily. None of the flared patients didn’t require restarting corticosteroids.ConclusionCorticosteroid-sparing control of inflammation was achieved in all patients. Data from our experience with adalimumab in patients with JIA-associated uveitis suggest that 45 % of patients can be successfully withdrawn from biologics for at least 24 months without disease recurrence.

Real-Life Effectiveness of Adalimumab Biosimilars in Patients with Chronic Plaque Psoriasis

IntroductionThe real-life effectiveness of adalimumab biosimilars in patients with psoriasis has rarely been investigated.ObjectiveTo investigate drug survival of adalimumab biosimilars in patients with chronic plaque psoriasis and factors associated with its discontinuation.MethodsWe carried out a retrospective observational study including all consecutive patients with chronic plaque psoriasis who initiated adalimumab biosimilar MSB11022 (Idacio), ABP501 (Amgevita), or SB5 (Imraldi) between 1 January 2018 and 1 January 2021. The 1-year drug survival of adalimumab biosimilar and independent factors associated with its discontinuation were investigated. Cox regression models were fit to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the risk of adalimumab discontinuation. A propensity score matching (PSM) model was adopted as sensitivity analysis.ResultsThe study involved a total of 410 patients with follow-up of 549.84 person-years, 271 (66.1%) men, a mean (SD) age of 51.8 (14.5) years, and a baseline PASI of 14.54 (5.02). Among adalimumab biosimilars, 250 (61%) patients received MSB11022, 98 (24%) received ABP501, and 62 (15%) received SB5. Drug survival of adalimumab biosimilars at 1 year was 81.5% in the overall study population. Obesity was associated with increased risk of adalimumab discontinuation (HR = 2.01; 95% CI 1.33–3.03), whereas psoriatic arthritis (aHR = 0.32; 95% CI 0.16–0.64) and receiving adalimumab as first systemic treatment (aHR = 0.44; 95% CI 0.27–0.70) were associated with lower risk.ConclusionThe real-life effectiveness of adalimumab biosimilars in patients with psoriasis is consistent with that previously reported for the originator.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00732-y.

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

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

Effectiveness of adalimumab for ulcerative colitis: A multicentre, retrospective study of clinical practice in Italy.

Adalimumab is used to treat ulcerative colitis, but additional effectiveness and safety data are needed. This retrospective study considered adults with ulcerative colitis treated with adalimumab at 19 hospitals. Clinical data were collected from the start of treatment, after 2, 6 and 12 months, and at the last visit. Outcome measures of effectiveness were treatment duration, reasons for discontinuation and colectomy. We studied 381 patients treated with adalimumab for a median of 12.1 months. Disease activity at the start of treatment was moderate to severe in 262 cases (68.8%) and endoscopic activity was moderate to severe in 339 cases (89.0%). At week 8, clinical responses were observed in 177 cases (46.5%) and clinical remission in 136 cases (35.7%). At 12 months, remission was observed in 128 cases (33.6%). Overall, 44 patients required colectomy, and 170 patients (44.6%) were still taking adalimumab when data were collected. Variables associated with adalimumab discontinuation were concomitant steroid treatment, severe clinical-endoscopic activity at baseline, need for adalimumab intensification and drug-related adverse events. Variables associated with colectomy were concomitant steroid treatment and high baseline C-reactive protein. Adalimumab is safe and effective for the treatment of ulcerative colitis.

P343 Changing the coUrse of cRohn’s disease with an Early use of adalimumab: The CURE study from the GETAID

Abstract Background Crohn’s disease (CD) is a disabling and destructive disease. Early intervention associated with tight monitoring appear to the best way to achieve deep remission and to prevent disease progression. Whether anti-TNF therapy can be interrupted in patients with early CD who have undergone a period of prolonged deep remission is unknown. The primary objective was to evaluate the sustained deep remission rate one year after discontinuation of a, 12-month course of adalimumab in adult patients with early CD who achieved deep remission at, 12 months and who were already in clinical remission and biomarker remission at, 6 months. Methods We carried out a multicentre prospective GETAID cohort study. All patients were naïve to biologics. The primary study endpoint was the percentage of patients with sustained deep remission at, 2 years after a, 12-month course of adalimumab in patients who achieved deep remission without therapeutic intervention (i.e. no surgery, no clinical flare-up, no introduction of CD-related treatment, no need for adalimumab optimization) AND who were already in clinical remission (CDAI &amp;lt;, 150) and biomarker remission (CRP &amp;lt;, 5 mg/L and fecal calprotectin &amp;lt;, 250) at, 6 months. The time to first relapse in patients who achieved deep remission after, 12-month therapy was also evaluated. Results A total of, 201 subjects were included between March, 2015 and March, 2019. The median disease duration was, 4 months. Overall, 56/183 (30.6%) of patients achieved deep remission at one year. From those who achieved deep remission, not lost to follow-up (n=8) and without protocol violation (n=2), 20/46 (43.48%) maintained their deep remission for one year after their treatment discontinuation (month, 24 of the study). Probabibility of relapse-free survival following adalimumab discontinuation in patients achieving deep remission at, 12 months was, 44.8% (Figure). Conclusion Three out of, 10 patients with early CD and naïve to biologics achieved deep remission at one year with adalimumab. Among these patients, about half of them maintained deep remission at, 2 years. The identification of factors associated with treatment success will allow identifying CD patients who can stop anti-TNF therapy after achieving deep remission.

P519 Analysis of the effectiveness and safety of switching from originator to biosimilar adalimumab in patients with Inflammatory Bowel Disease

Abstract Background Aims: 1) to compare persistence on adalimumab treatment over time in inflammatory bowel disease (IBD) patients who maintained adalimumab reference [non-switch cohort (NC)] vs. those who switched from adalimumab reference to adalimumab biosimilar [switch cohort (SC)]; 2) to compare loss of effectiveness of adalimumab treatment in the NC vs. SC; 3) to identify factors associated with discontinuation of adalimumab therapy; 4) to identify the factors associated with relapse in both cohorts; and 5) to evaluate the safety of both strategies. Methods Retrospective, observational, multicentre study. Patients under adalimumab reference who were in clinical remission at standard dose of adalimumab reference, and in whom adalimumab was the first anti-TNF administered, were included. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn’s disease, a partial Mayo score ≤2 in ulcerative colitis, and the absence of fistula drainage despite gentle finger compression in perianal disease. The follow-up time was at least 6 months since start of study observation period. The Kaplan-Meier method with log-rank test was used to evaluate the cumulative incidence of treatment discontinuation. Cox regression model was used to investigate factors potentially associated with therapy discontinuation. Results A total of 505 patients were included (45% women, 87% Crohn’s disease): 229 in the SC and 276 in the NC. The median follow-up was 12 months in the SC and 23 months in the NC (p&amp;lt;0.01). The incidence rate of adalimumab discontinuation was 10% [95% confidence interval (95%CI)=6–14%], and 7% (95%CI=5–10%) per patient-year in the SC and in the NC, respectively (p=0.035). The probability of maintaining adalimumab was 92% at 12 months and 77% at 24 months in the SC, and 97% at 12 months and 86% at 24 months in the NC. In the multivariable analysis, the switch to adalimumab biosimilar, adjusted for the level of C-reactive protein at baseline, was not associated with therapy discontinuation. 18% of the patients relapsed in the SC vs. 21% in the NC. The incidence of relapse was 17% (95%CI=13–23%) in the SC, and 12% (95%CI=10–16%) per patient-year in the NC (p=0.04). The cumulative incidence of relapse was 11% at 12 months and 38% at 24 months in the SC, and 11% at 12 months and 22% at 24 months in the NC. In the multivariable analysis, the switch to adalimumab biosimilar (adjusted by type of IBD) was associated with a higher risk of relapse (HR=1.5, 95%CI=1.008–2.36). 4% of the patients had adverse events in the SC vs. 8% in the NC (p&amp;gt;0.05). Conclusion The incidence rate of relapse was slightly higher in the SC; however, this fact had no impact on persistence on the drug. Switching from adalimumab reference to adalimumab biosimilar was safe.

Available Alternative Biologics and Disease Groups Influence Biologic Drug Survival in Patients with Psoriasis and Psoriatic Arthritis.

BackgroundFactors other than efficacy and safety could influence the survival of biologics in patients with psoriasis. Little is known about whether different disease groups affect drug survival of biologics or not.ObjectiveThis study aimed to investigate whether the availability of alternative biologics and disease groups could influence drug survival of biologics approved for psoriasis and psoriasis arthritis (PsA).MethodsA nationwide population-based retrospective cohort study was conducted using the Health Insurance and Review Assessment data in Korea between January 2009 and August 2019.ResultsThe drug survival analysis included 5,634 biologic episodes. Ustekinumab was the most frequently prescribed drug (n=2,488, 44.2%). Multivariable time-dependent Cox regression analysis showed that higher age, female sex, no comorbidity, concomitant cyclosporine or acitretin use, biologic-experienced and use of tumor necrosis factor (TNF)-α inhibitors were predictors of drug discontinuation. PsA was a predictor of drug persistence, particularly for TNF-α inhibitors. Ustekinumab and adalimumab discontinuation significantly increased after introducing secukinumab and ustekinumab, respectively.ConclusionThe availability of alternative biologics and disease groups affect biologic drug survival in patients with psoriasis and PsA.

P417 Long-term deep remission after adalimumab discontinuation in Crohn’s disease patients

Abstract Background Adalimumab is a safe and effective drug in treatment of Crohn’s Disease (CD). Current literature is not definitive regarding an exact timing for treatment withdrawal and disease relapses after drug discontinuation. Methods We conducted a single-centre, retrospective, observational cohort study involving patients affected by Crohn’s Disease (CD) treated with adalimumab. Of 575 patients treated with adalimumab for CD, 149 patients suspended treatment for stable deep remission (clinical steroid-free, biochemical, endoscopic remission defined as mucosal healing). Of these, 126 have a minimum follow up of 4 years, the other 23 where lost or finished the follow-up. Patients were assessed clinically, laboratoristically and endoscopically for 4 years. Relapse was defined as clinical (HBI &amp;gt; 4) and biochemical (PCR &amp;gt; 0.5 mg/dL). Results Of the 126 patients with 4 years follow-up, 64 (51%) maintained deep remission during the 4 year follow-up period. Of these, 38 (59%) were on exit-therapy with thiopurines. Twenty-seven patients (18%) had relapsed by year 1, 24 (18%) by year 2, 8 (6%) by year 3, and 1 (0.8%) by year 4. Relapses needed surgical therapy in 9 (15%) cases, whereas 36 (60%) were retreated with adalimumab and 4 (7%) with another biologic agent. The remaining 11 patients (18%) were treated only with a course of steroids. Conclusion Patients who suspend treatment with adalimumab for stable deep remission maintain remission in the long term in approximately half of cases. The majority of relapses occur in the first 24 months after discontinuation.

Possibility of treatment modification in patients with ankylosing spondylitis achieved of partial remission on treatment with adalimumab: Real practice data

Objective . To assess the duration of remission or inactive disease status in patients with achieved partial remission due to treatment with adalimumab (ADA) after it discontinuation. Materials and methods . A dynamic observation was conducted of 26 patients with ankylosing spondylitis with partial remission achieved due to prolonged use (for 24 months or more) of subcutaneous injections of 40 mg ADA once every two weeks. The discontinuation of ADA was carried out after a 3-4 month period of its use in de-escalation mode in the form of 1 injection (40 mg) once every 4 weeks. After discontinuation of ADA, patients continued to take non-steroidal anti-inflammatory drugs, sulfasalazine at a dose of 1.5-2 g per day (11 patients) and methotrexate 10 mg per week (3 patients). Assessment of the clinical, laboratory and ultrasonographic parameters of ankylosing spondylitis was carried out in 3, 6 and 12 months after the abolition of the ADA. Results and discussion . Among the observed patients, partial clinical remission of ankylosing spondylitis maintained after 6 months in 12 (46.2%) patients, and after 12 months - in 10 (38.5%). A low degree of ankylosing spondylitis activity (BASDAI &lt;4) was maintained for 6 months after the abolition of ADA in 14 (53.8%) patients, and after 12 months - in 12 (46.2%). Conclusion . Within 12 months after cancellation of ADA, ankylosing spondylitis exacerbation was observed in 53.8% of patients with initially achieved partial clinical remission.

P007 Anti-TNF-Therapy-Induced Leukocytoclastic Vasculitis: A Rare Complication in IBD patients.

BACKGROUND: Anti-tumor necrosis factor (TNF) therapies have been used successfully for more than two decades in the treatment of inflammatory bowel disease (IBD), such as Crohn disease (CD) and ulcerative colitis (UC). However, these drugs may be associated with several side effects, many of which are immune-mediated reactions such as paradoxical psoriasis, vasculitis and lupus-like syndromes. Vasculitis is an unusual complication paradoxically induced by TNF antagonists. Here, we report the clinical features, histologic findings, and outcomes of a series of patients with IBD identified with anti-TNF-therapy-induced vasculitis. METHODS: We present 5 cases of anti-TNF-therapy-induced vasculitis in IBD patients [ulcerative colitis (UC), n = 2; Crohn disease (CD), n = 3]. The patients who presented any other evident cause of vasculitis, such as infections, use of other non-anti-TNF drugs possibly associated with vasculitis, concomitant rheumatologic and autoimmune diseases or malignancies (except skin cancer) were excluded from this analysis. RESULTS: The total population of IBD patients evaluated in five tertiary referral centers was 2,442 cases. Of these 862 (35.3%) were using anti-TNF drugs, and therefore the prevalence of vasculitis in this IBD population was 0.58%. All patients were female, white and non-smokers. The mean age at vasculitis diagnosis was 32.2 years (range 20-38 years) and the mean age at IBD diagnosis was 25 years (18-36). The mean IBD duration was 7.2 years (1-19 years). The mean time between the start of biological therapy and the development of vasculitis was 30.8 months (12-60 months). Majority of patients were using adalimumab (80%, n = 4) and one patient was using infliximab (20%, n = 1). All patients were in deep remission at the time of diagnosis of vasculitis. Vasculitis involved the skin in all five patients: 4 presented with palpable purpura, 3 had ulcerated lesions, and 1 had erythematous macules. No patient exhibited extracutaneous manifestations. Of note, all 5 skin biopsy specimens showed leukocytoclastic vasculitis (LV) on histologic examination. Anti-TNF therapy was interrupted in all patients, and there was a remarkable response of LV with oral steroids. All patients had complete remission of skin lesions between 4 to 12 weeks after starting prednisone therapy. The average duration of steroid therapy was 3 months (range, 2.5 to 5.0 months). In order to keep the IBD treatment, three patients changed the biological mechanism of action (two patients with CD started ustekinumab and one patient with UC started vedolizumab). Two of the 5 patients were rechallenged with another anti-TNF-agent (i.e., infliximab) after discontinuation of adalimumab. None of patients presented vasculitis recurrence after switching the biological therapy during a mean follow up after LV diagnosis of 21.4 months (range, 12-28 months). CONCLUSION: LV is an uncommon complication of anti-TNF therapy in IBD patients. In this setting, clinicians should have a high index of suspicion for LV in patients developing unexplained cutaneous rash.

Mucosal microbiota and gene expression are associated with long-term remission after discontinuation of adalimumab in ulcerative colitis

Given that sustained remission is the ultimate treatment goal in the management of patients with ulcerative colitis (UC), the decision to stop anti-tumor necrosis factor (anti-TNF) treatment in UC patients is difficult. The aim of this study was to evaluate mucosal microbiota and gene expression profiles associated with long-term remission after discontinuation of anti-TNF therapy. In nine UC patients who received anti-TNF therapy for 6 months, microbiota isolated from uninflamed mucosae and gene expression in inflamed and uninflamed mucosae were investigated at week 0 and at week 24. At treatment initiation, Fusobacterium sp. and Veillonella dispar were over-represented in the relapse group compared with the non-relapse group. After treatment, Dorea sp. and Lachnospira sp. were over-represented in the non-relapse group. In the relapse group only, a significant shift in gut bacterial community composition was found between week 0 and week 24. Gene expression of ALIX (PDCD6IP) and SLC9A3 was significantly higher in the non-relapse group than in the relapse group. Lastly, we used machine learning methods to identify relevant gene signatures associated with sustained remission. Statistical analyses of microbiota and expression profiles revealed differences between UC patients who did or did not keep remission after the discontinuation of TNF inhibitors.Trial registration: UMIN000020785: Evaluation of adalimumab therapy in mesalazine-resistant or -intolerant ulcerative colitis; an observational study (EARLY study).

Chronic Recurrent Multifocal Osteomyelitis in Pediatric Crohn Disease, A Paradoxical Effect to Antitumor Necrosis Factor Alpha

Tumor necrosis factor-α (TNF-α) inhibitors have resulted in significant progress in the treatment of chronic inflammatory diseases. However, these therapies can lead to paradoxical immune-mediated inflammatory diseases with unknown physiopathology. For the first time, we report 3 cases of paradoxical chronic recurrent multifocal osteomyelitis after infliximab or adalimumab therapy during the course of Crohn disease. The patients complained of bone pain without joint involvement. At the time of diagnosis of paradoxical reaction, all patients were in remission due to anti-TNFα efficiency. Trough levels of anti-TNFα were in the expected range, and there were no anti–anti-TNFα antibodies. The duration of treatment was between 2 and 26 months. Other causes of CRMO were excluded. All patients recovered after discontinuation of infliximab (n = 2) or adalimumab (n = 1). The increasing use of these therapies leads to new descriptions of paradoxical effects, which clinicians should be aware of.