Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: a multicentre and retrospective study.

OBJECTIVE: To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels. METHODS: Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off: <200 (

Summary of certolizumab pegol in psoriasis including structural features, pharmacokinetics and treatment.

Psoriasis pathogenesis involves TNF-α, IL-23 and IL17, against which biologics have been highly effective. Among the five TNF-α inhibitors available for psoriasis, namely infliximab, adalimumab, etanercept, golimumab and certolizumab pegol (CZP), CZP has a unique mechanism of action due to its structure. As CZP lacks the Fc region, it does not cross the placenta and can be safely used in pregnant women. Its PEGylated nature allows for longer distribution time in tissues, potentially leading to a longer-lasting effect compared with other TNF-α inhibitors. In clinical trials, the efficacy of CZP on psoriasis skin symptoms and joint symptoms was comparable to other TNF-α inhibitors, with no discernible differences in safety profiles.

Psoriasis is a skin condition that affects the skin and causes joint problems. There are some medicines called TNF-α inhibitors that work well, especially for the joint issues. There are currently five TNF-α inhibitors available for treating psoriasis. One of these, certolizumab pegol, is different from the others. It lacks a specific part, which makes it less likely to pass through the placenta. This means it's safer for pregnant and breastfeeding women. Clinical trials have shown that certolizumab pegol is just as effective as other TNF-α inhibitors for treating the skin and joint symptoms of psoriasis. It's also equally safe.

Prediction of ineffectiveness of biological drugs using machine learning and explainable AI methods: data from the Austrian Biological Registry BioReg.

OBJECTIVES: Machine learning models can support an individualized approach in the choice of bDMARDs. We developed prediction models for 5 different bDMARDs using machine learning methods based on patient data derived from the Austrian Biologics Registry (BioReg). METHODS: Data from 1397 patients and 19 variables with at least 100 treat-to-target (t2t) courses per drug were derived from the BioReg biologics registry. Different machine learning algorithms were trained to predict the risk of ineffectiveness for each bDMARD within the first 26 weeks. Cross-validation and hyperparameter optimization were applied to generate the best models. Model quality was assessed by area under the receiver operating characteristic (AUROC). Using explainable AI (XAI), risk-reducing and risk-increasing factors were extracted. RESULTS: The best models per drug achieved an AUROC score of the following: abatacept, 0.66 (95% CI, 0.54-0.78); adalimumab, 0.70 (95% CI, 0.68-0.74); certolizumab, 0.84 (95% CI, 0.79-0.89); etanercept, 0.68 (95% CI, 0.55-0.87); tocilizumab, 0.72 (95% CI, 0.69-0.77). The most risk-increasing variables were visual analytic scores (VAS) for abatacept and etanercept and co-therapy with glucocorticoids for adalimumab. Dosage was the most important variable for certolizumab and associated with a lower risk of non-response. Some variables, such as gender and rheumatoid factor (RF), showed opposite impacts depending on the bDMARD. CONCLUSION: Ineffectiveness of biological drugs could be predicted with promising accuracy. Interestingly, individual parameters were found to be associated with drug responses in different directions, indicating highly complex interactions. Machine learning can be of help in the decision-process by disentangling these relations.

Retention rate of subcutaneous TNF inhibitors in axial spondyloarthritis in a multicentre study from the RIC-FRANCE network.

The objectives of our study were to assess retention rate, safety, and predictive factors for retention of subcutaneous (SC) TNF inhibitors (TNFi) (adalimumab (ADA), etanercept (ETN), golimumab (GOL), and certolizumab pegol (CZP)) in axial spondyloarthritis (axSpA) depending on the line of treatment in real-life conditions. A multicentre retrospective observational study was conducted including 552 patients fulfilling the ASAS criteria for axSpA followed in the RIC-France register who began SC-TNFi between 01/01/13 and 08/31/2018 for a total of 824 prescriptions. Taking all lines of treatment into account, GOL had a significantly higher retention rate compared with ADA, ETN, and CZP with a mean retention length of 59 months. As first-line bDMARDs, GOL had a significantly higher retention rate compared with ADA and ETN. ETN had the best retention rate when prescribed as at least 3rd bDMARD. Taking all lines of treatment into account, female sex, peripheral disease, BASDAI at initiation, and line of treatment were predictive factors for treatment cessation. Primary inefficiency was the most frequent reason for treatment cessation. In conclusion, GOL showed the highest retention rate in axSpA. Male sex, absence of peripheral disease, and early line of prescription were associated with better SC-TNFi retention in axSpA.

Characterization of anti-drug antibody dynamics using a bivariate mixed hidden-markov model by nonlinear-mixed effects approach.

Biological therapies may act as immunogenic triggers leading to the formation of anti-drug antibodies (ADAs). Population pharmacokinetic (PK) models can be used to characterize the relationship between ADA and drug disposition but often rely on the ADA bioassay results, which may not be sufficiently sensitive to inform on this characterization.In this work, a methodology that could help to further elucidate the underlying ADA production and impact on the drug disposition was explored. A mixed hidden-Markov model (MHMM) was developed to characterize the underlying (hidden) formation of ADA against the biologic, using certolizumab pegol (CZP), as a test drug. CZP is a PEGylated Fc free TNF-inhibitor used in the treatment of rheumatoid arthritis and other chronic inflammatory diseases.The bivariate MHMM used information from plasma drug concentrations and ADA measurements, from six clinical studies (n = 845), that were correlated through a bivariate Gaussian function to infer about two hidden states; production and no-production of ADA influencing PK. Estimation of inter-individual variability was not supported in this case. Parameters associated with the observed part of the model were reasonably well estimated while parameters associated with the hidden part were less precise. Individual state sequences obtained using a Viterbi algorithm suggested that the model was able to determine the start of ADA production for each individual, being a more assay-independent methodology than traditional population PK. The model serves as a basis for identification of covariates influencing the ADA formation, and thus has the potential to identify aspects that minimize its impact on PK and/or efficacy.

Methotrexate Safety and Efficacy in Combination Therapies in Patients With Early Rheumatoid Arthritis: A Post Hoc Analysis of a Randomized Controlled Trial.

OBJECTIVE: We investigated methotrexate safety and the influence of dose on efficacy outcomes in combination with three different biologic treatments and with active conventional treatment (ACT) in early rheumatoid arthritis (RA). METHODS: This post hoc analysis included 812 treatment-naïve patients with early RA who were randomized (1:1:1:1) in the NORD-STAR trial to receive methotrexate in combination with ACT, certolizumab-pegol, abatacept, or tocilizumab. Methotrexate safety, doses, and dose effects on Clinical Disease Activity Index (CDAI) remission were assessed after 24 weeks of treatment. RESULTS: Compared with ACT, the prevalence of methotrexate-associated side effects was higher when methotrexate was combined with tocilizumab (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.20-1.84) but not with certolizumab-pegol (HR 0.99, 95% CI 0.79-1.23) or with abatacept (HR 0.93, 95% CI 0.75-1.16). With ACT as the reference, the methotrexate dose was significantly lower when used in combination with tocilizumab (ß -4.65, 95% CI -5.83 to -3.46; P < 0.001) or abatacept (ß -1.15, 95% CI -2.27 to -0.03; P = 0.04), and it was numerically lower in combination with certolizumab-pegol (ß -1.07, 95% CI -2.21 to 0.07; P = 0.07). Methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the treatment combinations. CONCLUSION: Methotrexate was generally well tolerated in combination therapies, but adverse events were a limiting factor in receiving the target dose of 25 mg/wk, and these were more frequent in combination with tocilizumab versus ACT. On the other hand, methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the four treatment combinations at 24 weeks.

[Translated article] Risk-sharing agreement based on health outcomes for the treatment of moderate-severe psoriasis with certolizumab pegol.

OBJECTIVE: To provide evidence of the effectiveness of certolizumab pegol (CZP) in real clinical practice in adult patients with moderate-to-severe plaque psoriasis (PsO) in the context of a risk-sharing agreement (RSA). METHODS: Retrospective observational study based on variables collected in the RSA for treatment with CZP of adult patients with moderate-severe plaque PsO. Ten Spanish hospitals where the RSA was implemented participated. The percentage of patients who achieved the target clinical response of the RSA at the follow-up visit (week 16) was evaluated: absolute Psoriasis Area and Severity Index (PASI) value ≤3 for biologic naïve population, and ≤5 in case of previous failure to a single biologic drug. In addition, the improvement in the scores of other scales included in the study was analysed: Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), Physician's Global Assessment (PGA), and Nail Psoriasis Severity Index (NAPSI). A descriptive analysis was performed for the total population and by patient subgroups (naive vs. non-naive to biologic, male vs. female, and with vs. without discontinuation). RESULTS: Sixty-six patients were included, 12 men and 54 women. 90.9% achieved the target clinical response, with a mean reduction of 8 (-78.4%) absolute PASI points. Improvement was observed in BSA, PGA, NAPSI, and DLQI, with a reduction of 11.3 (-80.6%), 1.9 (-65.5%), 3.3 (-30.7%), and 9.0 (-66.4%) absolute value points, respectively. Despite not achieving the therapeutic target set in the RSA in 6 patients (9%) (the cost of the drug was assumed by the laboratory), only 2 (3%) discontinued treatment. CONCLUSION: Our study shows that CZP is effective in real clinical practice in patients with moderate-severe plaque PsO, with an improvement in absolute PASI and DLQI, as well as other scales, both for the total population and in the subgroups analysed. Nearly 91% of patients reached the therapeutic target fixed in the RSA. Implementing this type of agreement can provide a direct or indirect benefit for all the agents involved in the process, providing valuable information for decision-making.

Certolizumab treatment of localized pyoderma gangrenosum in a pregnant patient.

THE PURPOSE OF THE ARTICLE: Pyoderma gangrenosum (PG) is an ulcerating neutrophilic dermatosis with an incidence of 3-10 patients per million. PG equally affects patients of both sexes and of any age. Of these patients, 50-75% are associated with auto-immune disease. The lower extremities are the most commonly affected body parts. Minor trauma to the skin may result in the development of new lesions. Patients complain of chronic, nonhealing ulcers with associated pain. Treatment starts with systemic or intralesional corticosteroids, however, no official treatment protocol currently exists. Recent success has been found with biologic agents such as TNF-a inhibitor, although the treatment efficacy in these reports is limited. As for the pregnant patient, the drug selection is difficult. In this report, we want to assess the efficiency of certolizumab in the pregnant patient. RESULTS: We report a case of a patient with PG, who responded well to certolizumab, 400 mg as a booster dose, followed by 200 mg biweekly for 8 weeks. The lesions gradually resolved and followed up for 5months without side effect. In addition, we reviewed the literature and compared the current treatment efficiency in the treatment of PG. CONCLUSION: Certolizumab may be a promising therapeutic option for patients with severe PG.

A quantitative systems pharmacology model for certolizumab pegol treatment in moderate-to-severe psoriasis.

Background: Psoriasis is a chronic immune-mediated inflammatory systemic disease with skin manifestations characterized by erythematous, scaly, itchy and/or painful plaques resulting from hyperproliferation of keratinocytes. Certolizumab pegol [CZP], a PEGylated antigen binding fragment of a humanized monoclonal antibody against TNF-alpha, is approved for the treatment of moderate-to-severe plaque psoriasis. Patients with psoriasis present clinical and molecular variability, affecting response to treatment. Herein, we utilized an in silico approach to model the effects of CZP in a virtual population (vPop) with moderate-to-severe psoriasis. Our proof-of-concept study aims to assess the performance of our model in generating a vPop and defining CZP response variability based on patient profiles. Methods: We built a quantitative systems pharmacology (QSP) model of a clinical trial-like vPop with moderate-to-severe psoriasis treated with two dosing schemes of CZP (200 mg and 400 mg, both every two weeks for 16 weeks, starting with a loading dose of CZP 400 mg at weeks 0, 2, and 4). We applied different modelling approaches: (i) an algorithm to generate vPop according to reference population values and comorbidity frequencies in real-world populations; (ii) physiologically based pharmacokinetic (PBPK) models of CZP dosing schemes in each virtual patient; and (iii) systems biology-based models of the mechanism of action (MoA) of the drug. Results: The combination of our different modelling approaches yielded a vPop distribution and a PBPK model that aligned with existing literature. Our systems biology and QSP models reproduced known biological and clinical activity, presenting outcomes correlating with clinical efficacy measures. We identified distinct clusters of virtual patients based on their psoriasis-related protein predicted activity when treated with CZP, which could help unravel differences in drug efficacy in diverse subpopulations. Moreover, our models revealed clusters of MoA solutions irrespective of the dosing regimen employed. Conclusion: Our study provided patient specific QSP models that reproduced clinical and molecular efficacy features, supporting the use of computational methods as modelling strategy to explore drug response variability. This might shed light on the differences in drug efficacy in diverse subpopulations, especially useful in complex diseases such as psoriasis, through the generation of mechanistically based hypotheses.

Real-World Data of Adherence and Drug Survival of Biologics in Treatment-Naïve and Treatment-experienced Adult Patients with Rheumatoid Arthritis.

INTRODUCTION: Biologic disease-modifying anti-rheumatics drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are important treatments for rheumatoid arthritis (RA). As more of these drugs become available, there is a greater need to assess their real-world adherence and drug survival. METHODS: Treatment-naïve and treatment-experienced patients with RA who initiated treatment with bDMARDs and tofactinib during 2015-2018 in a large Israeli health maintenance organization were included. Adherence and time to treatment suspension were recorded. Odds for adherence were estimated using a multivariable logistic regression model. Risk for treatment suspension was estimated using a mixed-effect Cox proportional hazard model. RESULTS: The analysis included 753 eligible patients (61.8% treatment-naïve) treated with 1287 treatment episodes (tofacitinib 24.2%, tocilizumab 17.5%, etanercept 16.0%, adalimumab 10.4%, abatacept 9.9%, rituximab 9.0%, golimumab 6.9%, certolizumab pegol 3.6%, infliximab 1.9%, and sarilumab 0.5%). Good adherence was measured for almost all drugs, yet over 50% of all treatment episodes were suspended. Older age was associated with reduced risk for treatment suspension while higher number of primary care visits and higher Charlson's comorbidity score were associated with increased risk. Compared to etanercept, treatment with adalimumab, certolizumab, or rituximab was associated with increased risk for treatment suspension (HR 1.68 95% CI 1.27-2.22, HR 1.62 95% CI 1.00-2.60, and HR 2.72 95% CI 2.02-3.67, respectively). CONCLUSION: Treatment choice primarily depends on disease activity and prognosis. Real-world data, showing differences in drug survival of bDMARDs and tsDMARD, can also be used in the variety of considerations when choosing treatment. Future studies could separate patients with RA into subgroups, which would also account for potential drug survival differences and enable personalized therapy.

Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial.

BACKGROUND: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action. METHODS: Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025). RESULTS: Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%. CONCLUSIONS: Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments. TRIAL REGISTRATION NUMBER: NCT01491815.

Persistence Among Patients with Crohn Disease Previously Treated with an Anti-tumor Necrosis Factor Inhibitor and Switching or Cycling to Another Biologic Agent.

PURPOSE: Nonresponse to an anti-tumor necrosis factor (TNF) agent in patients with Crohn disease (CD) is often managed by either a switch to a different class of biologic (ie, ustekinumab, vedolizumab) or by cycling to another anti-TNF agent (ie, adalimumab, infliximab, certolizumab pegol). Persistence after a switch to a different biologic class or after cycling within the anti-TNF class was assessed in patients with nonresponse to an anti-TNF agent. METHODS: Adults with CD who discontinued from an anti-TNF agent and either switched to a different class of biologic (ie, anti-interleukin/integrin; the switching cohort) or cycled within the anti-TNF class (the cycling cohort) between September 23, 2016, and August 1, 2019, were selected from a commercial database. The index date was defined as the date of the first claim of the subsequent-line biologic (index biologic) after an anti-TNF. The switching and cycling cohorts were balanced with regard to baseline characteristics, using inverse probability of treatment weights-average treatment effect (IPTW-ATE). Persistence with the index biologic was defined as consistent use with no gaps of >120 days (ustekinumab, vedolizumab, infliximab) or of >60 days (adalimumab, certolizumab pegol) in biologic supply. Composite end points were persistence while being corticosteroid-free (defined as no use of corticosteroids with ≥14 days of supply after day 90 post-index) and persistence while on monotherapy (no immunomodulators/nonindex biologics). Weighted Kaplan-Meier and Cox models were used to assess outcomes at 12 months post-index. FINDINGS: There were 444 patients in the weighted switching cohort (mean age, 40.4 years; 56.3% female) and 441 in the weighted cycling cohort (mean age, 39.5 years; 58.4% female). At 12 months post-index, the rate of persistence with the index biologic was 75.7% in the switching cohort compared to 67.5% in the cycling cohort (log-rank P = 0.023); the rate of persistence while on monotherapy was 58.2% compared to 44.2%, respectively (log-rank P < 0.001). The rate of persistence was 44% greater in the switching compared to that in the cycling cohort (hazard ratio [HR] = 1.44; 95% CI, 1.11-1.88; P = 0.007); the rate of persistence while on monotherapy was 56% greater in the switching cohort (HR = 1.56; 95% CI, 1.28-1.90; P < 0.001). The between-cohort difference in persistence while being corticosteroid-free was not statistically significant (HR = 1.08; 95% CI, 0.89-1.32; P = 0.426). IMPLICATIONS: Patients with CD who switched to a different biologic class were more persistent than were patients who cycled to another anti-TNF agent. These findings may be useful for physicians when considering the treatment of patients who have experienced nonresponse or loss of response to the first-line anti-TNF agent.

Focus on Anti-Tumour Necrosis Factor (TNF)-α-Related Autoimmune Diseases.

Anti-tumour necrosis factor (TNF)-α agents have been increasingly used to treat patients affected by inflammatory bowel disease and dermatological and rheumatologic inflammatory disorders. However, the widening use of biologics is related to a new class of adverse events called paradoxical reactions. Its pathogenesis remains unclear, but it is suggested that cytokine remodulation in predisposed individuals can lead to the inflammatory process. Here, we dissect the clinical aspects and overall outcomes of autoimmune diseases caused by anti-TNF-α therapies.

Change in Serum KL-6 Level during Biologic Treatment for Psoriasis.

BACKGROUND: We previously analyzed data from blood examination screenings, including serum Krebs von den Lungen (KL) -6 level, before starting biologic treatment for psoriasis in a real-world setting. However, we did not follow change in KL-6 level after the initiation of biologics. Furthermore, there has been no follow-up study of certolizumab pegol, risankizumab, or tildrakizumab. This study evaluated change in serum KL-6 levels in patients during treatment with biologics, including certolizumab pegol, risankizumab, and tildrakizumab. METHODS: We analyzed data from 111 patients. Change in KL-6 level was regarded as significant if it increased to greater than 500 U/mL at least once and if the maximum level after treatment with biologics was at least 1.5 times that of the baseline level. RESULTS: KL-6 level significantly changed during treatment with TNF inhibitors, IL-17 inhibitors, and IL-23 inhibitors in 9 (20.9%), 2 (6.3%), and 2 (5.6%) patients, respectively. Mean age, mean baseline KL-6 level, and frequency of TNF inhibitor use were higher in patients with a significant change in KL-6 level than those in patients without a significant change. Ten patients had minor interstitial changes on chest CT scans but no clinical signs suggesting interstitial pneumonia. CONCLUSIONS: Older patients with psoriasis and high baseline KL-6 levels must be carefully monitored during treatment with biologics, especially TNF inhibitors. Monitoring of KL-6 level and chest CT scans is necessary to exclude the possibility of drug-induced interstitial pneumonia.

Efficacy and safety of biological DMARDs: a systematic literature review informing the 2022 update of the ASAS-EULAR recommendations for the management of axial spondyloarthritis.

OBJECTIVE: To update the evidence on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2022 update of the Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA. METHODS: Systematic literature review (2016-2021) on efficacy and safety of bDMARDs in axSpA (radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)). Eligible study designs included randomised controlled trials (RCTs), strategy trials and observational studies (the latter only for safety and extra-musculoskeletal manifestations). All relevant efficacy/safety outcomes were included. RESULTS: In total, 148 publications were included. Efficacy of golimumab and certolizumab was confirmed. Tumour necrosis factor inhibitor (TNFi) biosimilar-originator equivalence was demonstrated. RCT (n=15) data on efficacy of interleukin-17 inhibitors (IL-17i) demonstrated clinically relevant effects (risk ratio vs placebo to achieve ASAS40 response 1.3-15.3 (r-axSpA, n=9), 1.4-2.1 (nr-axSpA, n=2)). Efficacy of secukinumab/ixekizumab was demonstrated in TNFi-naïve and TNFi-inadequate responders. IL-23 and IL-12/23 inhibitors (risankizumab/ustekinumab) failed to show relevant benefits. Tapering of TNFi by spacing was non-inferior to standard-dose treatment. The first axSpA treat-to-target trial did not meet its primary endpoint, but showed improvements in secondary outcomes. No new risks were identified with TNFi use in observational studies (data lacking for IL-17i). Secukinumab (n=1) and etanercept (n=2) were associated with increased risk of uveitis in observational studies compared to monoclonal TNFi. CONCLUSIONS: New evidence supports the efficacy and safety of TNFi (originators/biosimilars) and IL-17i in r-axSpA and nr-axSpA, while IL-23i failed to show relevant effects. Observational studies are needed to confirm long-term IL-17i safety. PROSPERO REGISTRATION NUMBER: CRD42021257588.

Non-trough adalimumab and certolizumab drug levels associated with a therapeutic EULAR response in adherent patients with rheumatoid arthritis.

OBJECTIVES: Interventions aimed at increasing TNF-α inhibitor serum drug levels (SDLs) may improve treatment response; however, previous studies suggesting SDL cut-offs have not accounted for treatment adherence. The aim of this study was to establish the relationship between adalimumab/certolizumab SDLs and EULAR good vs non-/moderate response and to define SDL cut-offs associated with good response in fully adherent patients. METHODS: In a prospective observational study, 475 patients with RA were treated with certolizumab (n = 192) or adalimumab (n = 283). At baseline and 3, 6 and 12 months, patients had 28-joint DAS, self-reported treatment adherence and SDLs measured. Fully adherent patients were analysed as a subgroup. Follow-up data at 3, 6 and 12 months were analysed separately. Median SDLs were compared in good vs non-/moderate response patients and receiver operating characteristics (ROC) curves were used to establish cut-off SDLs. RESULTS: Fully adherent good responders had significantly higher median adalimumab/certolizumab SDLs compared with non-/moderate responders (P = 0.04 and P = 0.0005, respectively). ROC analysis reported 3 month non-trough adalimumab SDLs discriminated good vs non-/moderate response with an area under the curve (AUC) of 0.63 (95% CI 0.52, 0.75), with a cut-off of 7.5 mg/l being 39.1% specific and 80.9% sensitive. Similarly, 3 month non-trough certolizumab SDLs discriminated good vs non-/moderate response with an AUC of 0.65 (95% CI 0.51, 0.78), with a cut-off of 26.0 mg/l being 43.9% specific and 77.8% sensitive. CONCLUSION: In fully adherent patients, higher SDLs are detected in good responders, suggesting that interventions to improve SDLs, such as encouraging adherence, could improve treatment response. The 3 month non-trough SDL cut-offs of 7.5 mg/l for adalimumab and 26.0 mg/l for certolizumab may be useful in clinical practice.

Comparative analysis of low-field magnetic resonance imaging in patients with rheumatoid arthritis treated with certolizumab pegol or infliximab.

OBJECTIVES: The aim is to clarify the differences in magnetic resonance imaging (MRI) findings between rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP) and infliximab (IFX). METHODS: The study included RA patients who received CZP or IFX and were examined with low-field MRI (compacTscan; compact magnetic resonance imaging) at the beginning and again within 6 months of treatment initiation. Comparisons were made regarding background, clinical course, and differences in MRI findings following initiation of tumour necrosis factor inhibitors between the CZP and IFX treatment groups. MRI findings were evaluated by scoring erosion, bone marrow oedema (BME), and synovitis. RESULTS: Ten cases in CZP and 18 cases in IFX group were compared. The biologic disease-modifying antirheumatic drug-naïve rate in the IFX group was significantly higher than that in the CZP group. After 6 months, disease activities were significantly decreased from baseline in both groups. Erosion score did not change significantly in both groups after 6 months. BME score was significantly decreased in the CZP group after 6 months, whereas in the IFX group, there was no significant change. Synovitis score was significantly decreased in both groups after 6 months. CONCLUSIONS: The findings of our study suggest that, in patients with RA, CZP might improve BME more effectively than IFX.

Vedolizumabe comparado a agentes anti-TNF-α para indução e manutenção da remissão na doença de Crohn refratária a medicamentos biológicos: revisão rápida / Vedolizumab compared to anti-tnf-α agents for induction and maintenance of remission in biologic-refractory crohn's disease: a rapid review of systematic reviews

Vedolizumabe e anticorpos anti-TNF-α (infliximabe, adalimumabe, certolizumabe pegol). Indicação: Tratamento pessoas com doença de Crohn com falha a um agente biológico anti-TNF-α em tratamento prévio. Pergunta: Para adultos com doença de Crohn moderada a grave com falha terapêutica para anticorpos monoclonais anti-TNF-α, em tratamento de segunda linha, Vedolizumabe tem efeitos superiores aos anti-TNF-α para induzir e manter a remissão da doença? Objetivo: Investigar a eficácia e segurança do vedolizumabe, comparado aos agentes anti-TNF-α (infliximabe, adalimumabe, certolizumabe pegol), na indução e manutenção da remissão em pacientes refratários aos anti-TNF-α com doença de Crohn moderada a grave. Métodos: Revisão rápida de revisões sistemáticas. Levantamento bibliográfico foi realizado nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library e em registros de revisões sistemáticas e ensaios clínicos. Seguiu estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica dos estudos incluídos através da ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version) Resultados: Foi selecionada uma revisão sistemática, que atendida aos critérios de elegibilidade, mas nenhum ensaio clínico foi escolhido, pois não atendiam aos critérios de inclusão. Conclusão: Adalimumabe, disponível no Sistema Único de Saúde, é mais eficaz que vedolizumabe para induzir remissão clínica em pacientes tratados previamente com biológicos. Vedolizumabe não é mais eficaz que placebo para induzir remissão clínica. Vedolizumabe e adalimumabe são similares entre si e são mais eficazes que placebo para manter a remissão clínica. Não foram encontradas evidências comparando vedolizumabe a infliximabe ou certolizumabe pegol

Vedolizumab and anti-TNF-α antibodies (infliximab, adalimumab, certolizumab pegol). Indication: Treatment of people with Crohn disease who have failed an anti-TNF-α biological agent in previous treatment. Question: For adults with moderate to severe Crohn disease with treatment failure for anti-TNF-α monoclonal antibodies, in second-line treatment, does vedolizumab have superior effects to anti-TNF-α in inducing and maintaining disease remission? Objective: To investigate the efficacy and safety of vedolizumab, compared to anti-TNF-α agents (infliximab, adalimumab, certolizumab pegol), in the induction and maintenance of remission in moderate to severe Crohn disease refractory to anti-TNF-α previous treatment. Methods: Rapid review of systematic reviews. A bibliographic search was done in the PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library databases and in registries of systematic reviews and clinical trials. The search has followed predefined strategies. The methodological quality of the included studies was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: A systematic review was selected, which met the eligibility criteria, but no clinical trials were chosen as they did not meet the inclusion criteria. Conclusion: Adalimumab, available in the Brazilian Public Health System, is more effective than vedolizumab to induce clinical remission in patients previously treated with biologics. Vedolizumab is no more effective than placebo in inducing clinical remission. Vedolizumab and adalimumab are similar to each other and are more effective than placebo in maintaining clinical remission. No evidence was found comparing vedolizumab to infliximab or certolizumab pegol

Six months multicentre pilot open label single-arm study to evaluate patient experience, acceptability and satisfaction of switching certolizumab pegol from a prefilled syringe or autoinjection pen to an AVA® e-Device in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis patients.

WHAT IS KNOWN AND OBJECTIVE: The study aimed to assess acceptability and patient experience of Certolizumab (CZP) self-injection with AVA® and clarify patient device preference after switching CZP from the syringe or auto-injection pen to AVA® in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients. METHOD: A multicentre open-label, cross-sectional and prospective study among four Spanish hospitals was performed. Adult RA, PsA, axSpA patients treated for at least 6 months with the CZP syringe or pen were recruited. At the first visit, patients completed Pre-AVA® questionnaire. Patients were instructed on proper administration of CZP by AVA®. After 2 and 6 months of CZP self-injections using the AVA®, patient experience, adherence, preference and safety of each administration was assessed using post-AVA® questionnaire. RESULTS AND DISCUSSION: Thirty four patients were included (28 women). All patients self-administered CZP AVA® the full dose of CZP was injected. Patients reported >90% adherence to CZP AVA® assessed with the injection log. Pain at the injection site was reduced after switching to AVA®. Twenty nine patients preferred CZP AVA® and five patients preferred the CZP pen. No safety-related findings related to AVA® CZP administration were identified. WHAT IS NEW AND CONCLUSION: The AVA® is an advantageous delivery option for CZP in patients with RA, PsA, axSpA.