Tumor Necrosis Factor Inhibitor Therapy Research Articles

Characteristics associated with patient-reported treatment success in psoriatic arthritis.

To determine characteristics associated with patient-reported treatment success in psoriatic arthritis (PsA). Rheumatologist-diagnosed PsA patients fulfilling the CASPAR classification were recruited from a single center. PsA outcome measures included: 66/68 swollen/tender joint counts, Leeds/SPARCC dactylitis/enthesitis indices, psoriasis body surface area (BSA), and patient-reported outcomes (PROs) including PROMIS. The primary outcome was a patient-reported item: "Today, considering the level of control of your psoriatic arthritis and psoriasis, do you consider your treatment has been successful?" Descriptive and multivariate logistic regression analyses identified clinical predictors of patient-reported treatment success. Patient-reported reasons for lack of treatment success were explored. A total of 178 participants had a baseline visit. Mean (SD) CASPAR score was 3.7 (0.9), age 51.7 (13.5) years, and BMI 31.3 (7.2) kg/m2. Fifty-two percent were women, and 86.0% white. Treatment success was reported by 116/178(65%) patients in the analytic cohort. Among 76 patients who reported treatment failure, the most frequently selected reasons for lack of success were pain (n = 55, 72.4%), fatigue (n = 46, 60.5%), inflamed joints (n = 40, 52.6%), and stiffness (n = 40, 52.6%). Overall, 105 participants had complete data across variables in the logistic regression models. Patient-reported treatment success was independently associated with the 66-swollen/68-tender joint counts, psoriasis BSA, PROs (pain interference, physical function, fatigue), and TNF-inhibitor therapy, after controlling for BMI and demographics. Patient-reported treatment success in PsA may be achieved through improvement of inflammatory arthritis, psoriasis, pain, physical function, fatigue, and the use ofTNF-inhibitors. Patients reported treatment failure was most commonly due to symptoms of pain, fatigue and stiffness.

Comparison of Incidence or Recurrence of Anterior Uveitis in Patients with Ankylosing Spondylitis Treated with Tumor Necrosis Factor Inhibitors

Background: Anterior uveitis (AU) is a significant concern in patients with ankylosing spondylitis (AS), and the choice of tumor necrosis factor inhibitors (TNFi) as a treatment modality raises questions regarding its effects on AU. We compared the effects of TNFi on AU in patients with AS. Methods: Patients diagnosed with AS and treated with at least one TNFi, including anti-TNFα antibodies (adalimumab and infliximab) or a soluble TNF receptor molecule (etanercept), between January 2010 and December 2022, were retrospectively reviewed. We compared the recurrence rate of AU in patients with a history of uveitis and the incidence of new-onset AU in those without a history of uveitis among the three TNFi groups. We also compared the effects of two different TNFi agents in patients who underwent TNFi switching. Results: Within two years of treatment initiation, there was no significant difference in AU recurrence among the three TNFi groups. However, the incidence of new-onset AU was significantly higher in the etanercept group than in the adalimumab group (26.4% vs. 6.3%; p = 0.024). After two years, the AU recurrence rate was significantly lower in the adalimumab group than in the other groups (p < 0.001). Among patients who underwent anti-TNFi switching, adalimumab treatment was associated with a significantly lower incidence of uveitis than etanercept (p = 0.023). Conclusion: In the short-term period following TNFi therapy, etanercept induced new-onset AU more frequently than adalimumab in patients with AS. Adalimumab recipients experienced fewer AU recurrences during the subsequent long-term period compared to other TNFi recipients.

P1056 T cell responses to repeated SARS-CoV-2 vaccination and breakthrough infections in patients with inflammatory bowel disease on TNF inhibitor treatment, a prospective cohort study

Abstract Background Understanding T cell responses to SARS-CoV-2 immunisation in patients on immunosuppressive treatment is important for future vaccine recommendations. Our aim was to investigate the magnitude and quality of T cell responses following repeated SARS-CoV-2 vaccine doses and COVID-19 (breakthrough infections). Methods In this prospective, observational study of responses to SARS-CoV-2 vaccines (Nor-vaC)1, patients with inflammatory bowel disease (IBD) on TNF inhibitor (TNFi) therapy receiving up to four SARS-CoV-2 vaccine doses, and healthy controls receiving three vaccine doses were included. CD4 and CD8 T cell responses to SARS-CoV-2 peptides were measured by flow cytometry before and 2-4 weeks following vaccination and breakthrough infection. Antibodies to the receptor binding domain (RBD) of the Wuhan-Hu-1 and BA.1 (omicron) strains were measured. Results Between March 2, 2021, and December 20, 2022, 118 IBD patients, and 21 healthy controls were included in the study (Table). Following three vaccine doses, the humoral immune response was attenuated in IBD patients compared to healthy controls (median 3954 BAU/ml vs. 6280 BAU/ml, p=0.008). However, both the percentage of spike-specific T cells (CD4 median 0.11% vs. 0.10%, p=0.259, CD8 0.030% vs. 0.046%, p=0,333) and T cell polyfunctionality scores (a measure of quality of vaccine response) (CD4 median 0.403 vs. 0.371, p=0.386, CD8 0.105 vs. 0.101, p=0.871), showed comparable quality in IBD patients and controls following three doses. CD4 T cell responses increased rapidly and plateaued after two vaccine doses whereas CD8 T cell responses continued to improve up to four vaccine doses (Figure). Breakthrough infection in patients following the third or fourth vaccine dose increased CD8 polyfunctionality and generated broad CD4 and CD8 T cell responses against non-spike peptides. There was no difference in T cell responses between patients using TNFi mono- and combo therapy after primary vaccination (three vaccine doses) (p=0.648). Conclusion Despite attenuated antibody responses, IBD patients on TNFi treatment demonstrated T cell responses comparable to healthy controls following three SARS-CoV-2 vaccine doses. Repeated vaccination and breakthrough infection increased the quality and breadth of T cell responses, reaching a plateau. Distinguishing between CD4 and CD8 immune compartments and dynamics of activation after SARS-CoV-2 immunisation may provide nuanced understanding of protective cellular responses The study results indicate that IBD patients on TNFi treatment may in future follow the same recommendations for further SARS-CoV-2 vaccines as the general population. 1Clinialtrials.gov NCT04798625

P877 A comparison of vedolizumab and ustekinumab treatment in patients with Ulcerative Colitis after failure of treatment with tumor necrosis factor inhibitor

Abstract Background Data comparing vedolizumab (VDZ) and ustekinumab (UST) in patients with ulcerative colitis (UC) previously treated with tumor necrosis factor inhibitor (TNFi) and followed with regular serum-drug measurements are scarce. In the national pharmaceutical tender system of Norway, VDZ was listed as the first drug of choice after failed TNFi treatment from 2016 to 2019 and UST from 2020 to 2022. We aimed to compare drug persistence, effectiveness, drug dosing and disease activity in patients treated with VDZ or UST after failed TNFi therapy. Methods We included patients who had failed at least one TNFi and started either VDZ treatment (years 2016-2019) or UST (years 2020-2022). Patients were followed for one year after initiating the treatment or until discontinuation. Prospectively recorded data were obtained from the electronic patient journal (EPJ) and the local IBD-registry. Clinical remission was defined as 6-point Mayo Score ≤1, and biochemical remission was defined as CRP<5 mg/L and FC<250 µg/g. Patients were followed with regular serum-drug measurements and dose adjustments were made at the discretion of the treating physician based on serum-drug measurements and clinical activity at follow-up visits. Wilcoxon signed rank and Mann Whitney U test were used to assess differences in paired and unpaired data, respectively. Results A total of 116 patients were included, 59 treated with VDZ and 57 with UST. At 52 weeks, there was no difference in estimated drug persistence with 85% [73-92] for VDZ and 92% [80-96] for UST. Clinical remission increased significantly in both groups (Table 1), and no difference was found between UST and VDZ for clinical remission at week 0 and 52 (OR=2.1 [0.9-4.5] and OR=0.9 [0.3-2.3]). Contrary to the VDZ group, there was a significant decrease in CRP from week 0 to 52 in the UST group, while FC decreased significantly in both groups (Table 1). The proportion of patients in biochemical remission increased in the UST group while there was no significant change in the VDZ group. Significantly more patients treated with UST received an intensified treatment regime at 52 weeks (interval less than eight weeks) compared to VDZ treated patients (87% (95% CI [74-94]) vs 59% (95% CI [45-72])). Conclusion This study demonstrates that one-year drug persistence and clinical remission were high and comparable in both UST and VDZ treated UC patients with previous TNFi failure. Treatment with UST, but not VDZ, was associated with a significant increase in the proportion of patients in biochemical remission from induction to 52 weeks. However, a significantly larger proportion of patients treated with UST received intensified dosing at 52 weeks compared with VDZ treated patients.

DOP15 Results of a pragmatic multicentred randomised controlled trial investigating the use of personalised golimumab dosing in Ulcerative Colitis: the GOAL-ARC study (GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis)

Abstract Background Ulcerative Colitis (UC) is a chronic inflammatory bowel disease (IBD) often leading to impaired quality of life in affected patients. Current treatment modalities include anti-tumour necrosis factor (anti-TNF) monoclonal antibodies including infliximab, adalimumab and golimumab (GLM). RCT show higher trough drug levels (DL) following induction are associated with enhanced rates of remission in maintenance. GOAL-ARC is a pragmatic RCT to examine if dose optimisation of GLM following induction in response to suboptimal DL or persistently raised faecal calprotectin (FCP) improves rates of patient continuous clinical response (pCCR) and reduces maintenance disease activity in UC Methods A pragmatic randomised, multi-centre two-arm investigator initiated trial (NCT0268772) . Population – Patients with moderate to severe UC requiring TNF inhibitor therapy. Intervention - one arm receiving GLM treatment as per SMPC and one arm with dose optimisation of GLM based on FCP and DL from week 6 according to a dedicated algorithm. Eligible patients were randomised in a 1:1 ratio to 1 of 2 treatment groups. Study Duration - 46 weeks. Primary end-point pCCR = absence of flare defined as no increase in modified partial Mayo (MPM) score of 2 points from week 14-46 (requiring treatment intervention). Secondary endpoints included rate of clinical response to induction (week 14), defined as a drop of MPM of 2 points or decrease of ≥30% from baseline and level of FCP and rate of mucosal healing (Mayo endoscopic subscore of 0/1) at Wk 46 Results 107 patients were enrolled (target enrolment n=135, study enrolment terminated early due to recruitment problems during and following C19 pandemic). 97 patients (median age 42) were randomised, with one patient subsequently excluded due to ineligibility. Of 96 evaluable patients, 46 were randomised to SMPC treatment and 50 were randomised to the intervention. Baseline characteristic were comparable. 28/46 (61%) achieved wk 14 clinical response with SMPC and 19/46 (41%) met the primary endpoint (pCCR wk 14-46). In the intervention arm 28/50 (56%) achieved wk 14 clinical response and 24/50 (48%) met the primary endpoint (pCCR wk 14-46). The difference between groups in the rates of pCCR was 6.7% (95% CI:-0.15,0.29) in favour of the intervention and was not statistically significant. No safety signal associated with the intervention was observed. Conclusion In a pragmatic RCT no significant increase in the rate of pCCR was observed with personalised dosing of GLM for treatment of moderate to severe UC. A numerical trend towards reduced loss of response during maintenance (20% with SMPC versus 8% with intervention) is observed with personalised dosing of GLM suggesting this strategy may be beneficial in some patients

Real-World Treatment and Care Patterns in Patients With Rheumatoid Arthritis Initiating First-Line Tumor Necrosis Factor Inhibitor Therapy in the United States.

Treatment guidelines for rheumatoid arthritis (RA) recommend targeting low disease activity or remission and switching therapies for patients not reaching those targets. We evaluated real-world use of disease activity measures, treatment discontinuation, and switching patterns among patients with RA initiating a first-line tumor necrosis factor inhibitor (TNFi). Data from adult patients with RA initiating a first-line TNFi were collected from the American Rheumatology Network (January 2014-August 2021). The proportion of patients with recorded disease activity scores (Clinical Disease Activity Index [CDAI] or Routine Assessment of Patient Index Data 3 [RAPID3]) at TNFi initiation was assessed. Among patients with moderate or severe RA at TNFi initiation, reasons for discontinuation and subsequent advanced therapy were evaluated. Among TNFi initiators (n=15,182), 44.8% recorded a CDAI/RAPID3 score at treatment initiation; of those who did not, 47.0% had recorded a tender and/or swollen joint count or pain score. Among patients with moderate or severe RA (n=1,651), 52% discontinued their initial TNFi during follow-up, of which 15%, 46%, 28%, and 12% initiated the same TNFi, another TNFi, a non-TNFi biologic, or a Janus kinase inhibitor, respectively. The proportion of patients restarting the same TNFi or initiating another TNFi varied according to TNFi discontinuation reason. In clinical practice, over half of patients with RA initiating a first-line TNFi did not have baseline disease activity assessments. Many patients cycled through TNFi despite citing lack of efficacy as the most common reason for discontinuation. Consistent, objective monitoring of treatment response and timely switch to effective therapy is needed in patients with RA.

Lower body mass and lower adiposity are associated with differential responses to two treatment strategies for rheumatoid arthritis

PurposeTo determine if body mass index (BMI) and adipokine levels identify rheumatoid arthritis (RA) patients most likely to benefit from initiation of tumour necrosis factor inhibitors (TNFi) after methotrexate inadequate...

Screening practices, efficacy, safety and adherence to biologic therapies in a South African tertiary hospital

IntroductionThe high cost and concern of adverse events, particularly infections, limit the use of biologic therapies. We undertook this retrospective study to document their use for immune-mediated diseases, and explore the screening practices, efficacy, safety, and adherence to bDMARDs in a tertiary hospital.MethodsA folder review of all adult and paediatric patients treated for IMDs with bDMARDs. Changes in disease activity were measured by disease-specific tools at 6, 12, 24-months and at the last available visit, and patient adherence to bDMARDs was explored by folder and pharmacy record review.ResultsWe studied 120 folders; 145 bDMARDs were prescribed (23 patients switched bDMARD). BDMARDs prescribed included tumour necrosis factor inhibitors (TNFi) (76), rituximab (54), tocilizumab (9), anakinra (3), abatacept (1), ustekinumab (1) and tofacitinib (1). The vast majority of patients had an excellent response and achieved low disease activity or remission at their last available visit. Adverse events included severe infection (9) including two cases of tuberculosis (TB), mild skin reaction (6) and severe infusion reactions (4). Therapy was discontinued in 13 patients, most commonly due to infection (5), lack of response (4), or poor adherence (3). Poor adherence was noted in 8/120 (6.7%). Complete latent TB infection screening was performed in only 35 patients (29.2%). Screening for Hepatitis B, C and HIV was performed in 28 (23.3%), 62 (51.7%) and 61 (50.8%) patients, respectively. Only 20.8% and 20.0% received the influenza and pneumococcal vaccination.Discussion and conclusionBiologic therapy was effective, and the most important serious adverse effect was infection, which was significantly associated with TNFi therapy. Vaccination and screening for TB, viral hepatitis and HIV was suboptimal. Of concern, poor adherence to bDMARDs was frequently encountered.

S87 Use of Tofacitinib as an Alternative in Moderately Severe Ulcerative Colitis in Pediatric Patients Refractory to Tumor Necrosis Factor Inhibitor Therapy

S87 Use of Tofacitinib as an Alternative in Moderately Severe Ulcerative Colitis in Pediatric Patients Refractory to Tumor Necrosis Factor Inhibitor Therapy

[Translated article] Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases

BackgroundTumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. Material and methodsRetrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. ResultsWe collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. ConclusionsParadoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.

Effect of Secukinumab and Tumor Necrosis Factor Inhibitors on Humoral Response to BNT162b2 mRNA Vaccine in Patients With Spondyloarthritis Compared to Immunocompetent Controls.

To assess the humoral response to the BNT162b2 mRNA vaccine among patients with spondyloarthritis (SpA) receiving secukinumab (SEC) compared to those receiving tumor necrosis factor inhibitors (TNFi) and immunocompetent controls. Consecutive patients with psoriatic arthritis or axial SpA receiving SEC (n = 37) or TNFi (monotherapy, n = 109; + methotrexate [MTX], n = 16), immunocompetent controls (n = 122), and patients with rheumatoid arthritis (RA) receiving TNFi therapy (controls, n = 50) were vaccinated with 2 or 3 doses of the BNT162b2 vaccine. We evaluated humoral response, adverse events, and disease activity, and monitored for breakthrough coronavirus disease 2019 (COVID-19) postvaccination. The 2-dose vaccine regimen induced a comparable seropositive response in all study groups. S1/S2 antibody titers (in binding antibody units/mL; mean [SD]) were higher in the SEC group vs the TNFi + MTX-SpA and TNFi-RA groups (192.5 [68.4] vs 104.6 [46.9], P < 0.001, and 143.1 [81.9], P = 0.004). After 6 months, 96.3%, 96.6%, and 80.9% of the SEC, immunocompetent, and TNFi monotherapy-SpA groups (P = 0.10), respectively; 66.7% of the TNFi + MTX-SpA group (P = 0.03); and 63% of the TNFi-RA group (P = 0.004) remained seropositive. S1/S2 antibody titer decline was steeper in the TNFi groups than the SEC group. After the third dose, 100% of the SpA and immunocompetent and 88.9% of the TNFi-RA (P = 0.25) groups were seropositive. Rate of breakthrough COVID-19 infection was higher in the TNFi groups than in the SEC group (36-37.5% vs 10.8%). No significant between-group differences were observed for postvaccination disease activity and adverse events. SEC did not interfere with the immunogenic response to BNT162b2 vaccine in patients with SpA; however, TNFi therapy was associated with lower S1/S2-antibody titers, faster decline, and higher rate of breakthrough infections.

Occurrence and prediction of flare after tapering of TNF inhibitors in patients with axial spondyloarthritis.

Patients with axial spondyloarthritis (axSpA) in clinical remission tapered Tumor Necrosis Factor inhibitor (TNFi) therapy according to a clinical guideline. During 2-years' follow-up, we aimed to investigate flare frequency, dose at which flare occurred, type of flare and predictors thereof. Patients in clinical remission (Bath ankylosing spondylitis disease activity index (BASDAI)<40, physician global score<40 and without disease activity the previous year) tapered TNFi to 2/3 standard dose at baseline, 1/2 at week (w) 16, 1/3 at w32 and discontinuationed at w48. Flare was defined as: BASDAI flare (BASDAI≥40 and Δ≥20) and/or clinical flare (development of inflammatory back pain, musculoskeletal or extra-articular manifestations and/or ASDAS-CRP increase ≥0.9) and/or MRI flare (≥2 new/worsened inflammatory lesions). Of 108 patients, 106 (99%) flared before 2 years: 29 patients (27%) at 2/3 standard dose, 21 (20%) at 1/2 dose, 29 (27%) at 1/3 dose and 27 (25%) after discontinuation. One-hundred-and-five (99%) had clinical flare, 25 (24%) BASDAI flare and 23 (29% of patients with MRI) MRI flare. Forty-one patients (41%) fulfilled the ASAS-definition of clinically important worsening (≥0.9 increase since baseline). Higher baseline physician global score was an independent predictor of flare after tapering to 2/3 (Odds ratio=1.19 (95% Confidence Interval=1.05-1.41);p=0.011). Changes in clinical and/or imaging variables in the 16 weeks prior to tapering did not predict flare. Almost all (99%) axSpA patients in clinical remission flared during tapering to discontinuation, but above half not before receiving 1/3 dose or less. Higher physician global score was an independent predictor of flare.

Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial

ObjectivesMany patients with rheumatoid arthritis (RA) require treatment with tumour necrosis factor inhibitor (TNFi) to reach remission. It is debated whether tapering of TNFi to discontinuation should be considered in...

Retention rate of tumor necrosis factor inhibitors, anti-interleukin 17, and anti-interleukin 12/23 drugs in a single-center cohort of psoriatic arthritis patients.

The objective of this study was to evaluate biological disease-modifying anti-rheumatic drugs (bDMARDs) survival in several therapy courses of patients affected by psoriatic arthritis (PsA) and to compare tumor necrosis factor inhibitors (TNFi) and non-TNFi retention rates. A total of 241 bDMARD therapy courses (155 TNFi drugs, 65 anti-interleukin (IL)-17 drugs, and 21 anti-IL12/23) were analyzed. Bivariate analyses were performed to assess the presence of demographic and clinical features, as well as comorbidities, associated with bDMARD discontinuation in TNFi and non-TNFi groups. In the bivariate analyses of TNFi and non-TNFi groups, we found a lower age at the start of TNFi therapy in the former group [46 years, interquartile range (IQR) 45-54 vs 50.5 years, IQR 42-61; p=0.004] as well as a lower proportion of patients with skin psoriasis (65.8% vs 88.4%; p<0.001). Survival analysis showed no significant differences between TNFi and non-TNFi groups. Cox regression found fibromyalgia as a predictor of drug failure [hazard ratio (HR) 3.40, confidence interval (CI) 1.92-6.03; p<0.001] and first-line bDMARDs as a protective factor (HR 0.46, CI 0.25-0.88; p=0.019). Lastly, among TNFi courses, fibromyalgia was associated with drug suspension (HR 6.52, CI 3.16-13.46; p<0.001), while only a trend of significance for skin psoriasis as a risk factor for drug failure was shown (HR 2.38, CI 1.00-5.66, p=0.05). This study provides information about clinical and demographic factors associated with retention rates of bDMARDs from a real-life, single-center cohort of PsA patients.

Efectos adversos cutáneos inmunomediados por los anti-TNF: revisión de 30 casos

BackgroundTumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. Material and methodsRetrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. ResultsWe collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. ConclusionsParadoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.

Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: results from 13 European registries.

In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (<2 years as reference): 2-3 years: 1.20 (0.89-1.60), 4-9 years: 1.42 (1.09-1.84), ≥10 years: 1.66 (1.26-2.20); men vs women: 1.85 (1.54-2.23); CRP of >10 vs ≤10 mg/l: 1.52 (1.22-1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98-0.99). Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.

Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme

ObjectiveIncreased risk of serious adverse events (AEs) was reported for tofacitinib relative to tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis (RA) aged ≥50 years enriched for cardiovascular...

Incident psoriasis under treatment with tumor necrosis factor-α inhibitors in juvenile idiopathic arthritis patients-analysis of the BiKeR registry.

The efficacy of tumor necrosis factor inhibitors (TNFi) for the treatment of psoriasis is well established, but patients may develop psoriasis for the first time while on TNFi as a paradoxical effect. Limited data on this association in patients with juvenile idiopathic arthritis (JIA) are available. Safety data from patients registered to the German Biologics registry (BiKeR) were analyzed. Patients were grouped by treatment regime: single TNFi, multiple TNFi, non-TNFi biologics or bDMARD-naïve control group receiving methotrexate. TNFi-associated psoriasis was defined as incident diagnosis of psoriasis after starting TNFi treatment. Patients with a history of psoriasis or psoriasis arthritis prior to TNFi therapy were excluded. Event rates using AEs reported after first dose were compared by Wald's test. A total of 4149 patients were treated with a TNFi (etanercept, adalimumab, golimumab, infliximab), 676 with a non-TNFi biologic (tocilizumab, abatacept, anakinra, canakinumab) and 1692 with methotrexate only. A total of 31 patients were diagnosed with incident psoriasis while on one of the above treatments. Compared with methotrexate, psoriasis was more frequent in the TNFi cohorts (RR 10.8, p = 0.019), specifically in the subgroup of TNF antibodies (RR 29.8, p = 0.0009), whereas no significant signal was observed with etanercept. Also, non-TNFi-treated patients presented high incident psoriasis rates (RR 25.0, p = 0.003). Our findings indicate a higher rate of incident psoriasis in JIA patients treated with TNFi monoclonal antibodies or non-TNFi biologic treatment. JIA patients receiving monoclonal antibody TNFi or non-TNFi bDMARD should be monitored for incident psoriasis. Medication change, if topical skin treatment remains insufficient, may be considered.

Acute heart failure as an adverse event of tumor necrosis factor inhibitor therapy in inflammatory bowel disease: A review of the literature.

Tumor necrosis factor inhibitors (anti-TNFs) are widely used therapies for the treatment of inflammatory bowel diseases (IBD); however, their administration is not risk-free. Heart failure (HF), although rare, is a potential adverse event related to administration of these medications. However, the exact mechanism of development of HF remains obscure. TNFα is found in both healthy and damaged hearts. Its effects are concentration- and receptor-dependent, promoting either cardio-protection or cardiomyocyte apoptosis. Experimental rat models with TNFα receptor knockout showed increased survival rates, less reactive oxygen species formation, and improved diastolic left ventricle pressure. However, clinical trials employing anti-TNF therapy to treat HF had disappointing results, suggesting abolishment of the cardioprotective properties of TNFα, making cardiomyocytes susceptible to apoptosis and oxidation. Thus, patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy. This review aims to discuss adverse events associated with the administration of anti-TNF therapy, with a focus on HF, and propose some approaches to avoid cardiac adverse events in patients with IBD.

Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study

Objectives To assess the efficacy and safety of olokizumab (OKZ), a monoclonal antibody against the interleukin-6 (IL-6) cytokine, versus placebo (PBO) in patients with prior inadequate response to tumour necrosis factor inhibitors (TNFi-IRs).Methods In this 24-week multicentre, placebo-controlled, double-blind study, the patients were randomised in a 2:2:1 ratio to receive subcutaneously administered OKZ 64 mg once every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or PBO plus methotrexate. At week 16, the patients on PBO were randomised to receive either OKZ regime. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. Disease Activity Score 28-joint count C-reactive protein (DAS28 (CRP)) &lt;3.2 at week 12 was the major secondary efficacy endpoint. Safety and immunogenicity were assessed.Results In 368 patients randomised, ACR20 response rates were 60.9% in OKZ q2w, 59.6% in OKZ q4w and 40.6% in PBO (p&lt;0.01 for both comparisons). Achievement of DAS28 (CRP) &lt;3.2 was significantly different, favouring the OKZ arms. Improvements in efficacy and patientreported outcomes were maintained throughout 24 weeks and were noted after week 16 in patients who switched from PBO.Dose-related treatment-emergent serious adverse events were 7% in OKZ q2w, 3.2% in OKZ q4w and none in the PBO group.Conclusions Direct inhibition of IL-6 with OKZ resulted in significant improvements in the signs and symptoms of rheumatoid arthritis compared with PBO in TNFi-IR patients with a similar safety profile as observed for monoclonal antibodies to the IL-6 receptor.