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Objectives: To analyze the impact of different patterns of healthcare delivery on remission of rheumatoid arthritis (RA) patients treated with targeted therapies during the first wave (2020) and second/third waves (2021) of the pandemic compared to the pre-pandemic period (2019). Methods: In this observational real-life study, data from RA patients treated with biologic or targeted synthetic drugs were extracted from a longitudinal registry. Clinical Disease Activity Index (CDAI) was analyzed in the same period from the 22nd of February to the 18th of May for three consecutive years. These three periods were characterized by different patterns of healthcare delivery: (1) before the pandemic (2019) only in-person visits, (2) during the first wave (2020) both in-person visits and telehealth, and (3) during the second/third waves (2021) only in-person visits. A generalized linear model with the binomial error was fitted to evaluate the difference in the proportion of patients in CDAI remission. Quantile regression was used to compare the median of CDAI in difficult-to-treat (D2T) patients. Results: In the three periods, we included 407, 450, and 540 RA patients respectively. The percentages of patients in CDAI remission were similar in the three periods (prevalence ratio 1.07, p value 0.423 between 2020 and 2019, and 1.01, p-value 0.934 between 2021 and 2019). The CDAI remission rate was 40.55% (N = 163), 43.18% (N = 155) and 40.82% (N = 220) in 2019, 2020 and 2021, respectively. Among our cohort of D2T patients, CDAI remission was similar across the three periods (N = 30, 22.22%; N = 27, 23.68%; and N = 34, 21.52% respectively). Conclusion: Although the pandemic has imposed changes in our healthcare delivery, these different strategies seem to be effective in ensuring satisfactory management of RA treated with targeted therapies. The approaches modulated in the context of the different periods have been a feasible compensation for ensuring disease control even in D2T patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate in patients with rheumatoid arthritis (RA) the impact of EMA recommendations on the real-life prescription of JAK inhibitors (JAKis) and the use of the Expanded Risk Score in RA (ERS-RA) to quantify the risk of major adverse cardiac events (MACE). Methods: We conducted a retrospective analysis of real-life RA patients treated with JAKis. Patients were classified as ineligible for JAKis if they fulfilled EMA criteria (>65 years-old, history of malignancy, or increased risk of venous thromboembolic events [VTE] or MACE including smoking). Risk of MACE was defined according to ORAL Surveillance trial inclusion criteria (ORALSURV) or by using the ERS-RA. Results: Of 194 patients enrolled, 57.9% were classified as ineligible according to EMA definition (ORALSURV criteria). The most frequent reason for ineligibility was increased MACE risk (70.2%), followed by age>65 (34.2%), smoking (30.7%), and increased risk of VTE (20.2%) or malignancy (7%). The use of the ERS-RA reduced the rate of patients carrying an increased CV risk to 18.6% (p<0.001 versus ORALSURV), leading to 46.4% overall ineligible patients. Over a drug-exposure of 337 patient/years, we observed 2 VTE, one MACE (non-fatal stroke), and one solid malignancy (all in the group of patients classified as ineligible according to both the definitions). Conclusions: Rigorous application of EMA indications in clinical practice could result in the exclusion of a large proportion of RA patients from treatment with JAKis. A proper quantification of the risk for MACE by dedicated tools as ERS-RA is advocated to better tailor the management of RA. [ABSTRACT FROM AUTHOR]

Rheumatoid Arthritis (RA) is a systemic disease with many different clinical phenotypes. RA could be classified according to disease duration, seropositivity for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), joint subtype, clinical behaviourbehavior and many other subgroups. In this review, we summarize and discuss the multifaceted aspects of RA, focusing on the relationship between autoimmunity status and clinical outcome, achievement of remission and influence on treatment response, from the 2022 International GISEA/OEG Symposium. [ABSTRACT FROM AUTHOR]

While precision medicine is still a challenge in rheumatic disease, in recent years many advances have been made regarding pathogenesis, the treatment of inflammatory arthropathies, and their interaction. New insight into the role of inflammasome and synovial tissue macrophage subsets as predictors of drug response give hope for future tailored therapeutic strategies and a personalized medicine approach in inflammatory arthropathies. Here, we discuss the main pathogenetic mechanisms and therapeutic approaches towards precision medicine in rheumatoid arthritis from the 2022 International GISEA/OEG Symposium. [ABSTRACT FROM AUTHOR]

The term "axial spondyloarthritis" (axSpA) refers to a group of chronic rheumatic diseases that predominantly involve the axial skeleton and consist of ankylosing spondylitis, reactive arthritis, arthritis/spondylitis associated with psoriasis (PsA) and arthritis/spondylitis associated with inflammatory bowel diseases (IBD). Moreover, pain is an important and common symptom of axSpA. It may progress to chronic pain, a more complicated bio-psychosocial phenomena, leading to a significant worsening of quality of life. The development of the axSpA inflammatory process is grounded in the complex interaction between genetic (such as HLA B27), epigenetic, and environmental factors associated with a dysregulated immune response. Considering the pivotal contribution of IL-23 and IL-17 in axSpA inflammation, the inhibition of these cytokines has been evaluated as a potential therapeutic strategy. With this context, here we discuss the main pathogenetic mechanisms, therapeutic approaches and the role of pain in axSpA from the 2022 International GISEA/OEG Symposium. [ABSTRACT FROM AUTHOR]

Musculoskeletal involvement is one of the most common manifestations of systemic lupus erythematosus (SLE), with a negative impact on both quality of life and overall prognosis. SLE arthritis can be classified into three different subtypes, with different prevalence and characteristic biomarkers and MRI findings. Identifying the pathogenetic mechanisms underlying musculoskeletal manifestations' development is crucial to develop therapeutic strategies to suppress synovial inflammation, prevent erosions and deformities, and improve SLE patients' quality of life. Hence, here we discuss the main pathogenetic mechanisms and therapeutic approaches of musculoskeletal manifestations of SLE from the 2022 International GISEA/OEG Symposium. [ABSTRACT FROM AUTHOR]

COVID-19 has proven to be particularly serious and life-threatening for patients presenting with pre-existing pathologies. Patients affected by rheumatic musculoskeletal disease (RMD) are likely to have impaired immune responses against SARS-CoV-2 infection due to their compromised immune system and the prolonged use of disease-modifying anti-rheumatic drugs (DMARDs), which include conventional synthetic (cs) DMARDs or biologic and targeted synthetic (b/ts) DMARDs. To provide an integrated analysis of the immune response following SARS-CoV-2 infection in RMD patients treated with different classes of DMARDs we carried out an immunological analysis of the antibody responses toward SARS-CoV-2 nucleocapsid and RBD proteins and an extensive immunophenotypic analysis of the major immune cell populations. We showed that RMD individuals under most DMARD treatments mount a sustained antibody response to the virus, with neutralizing activity. In addition, they displayed a sizable percentage of effector T and B lymphocytes. Among b-DMARDs, we found that anti-TNFα treatments are more favorable drugs to elicit humoral and cellular immune responses as compared to CTLA4-Ig and anti-IL6R inhibitors. This study provides a whole picture of the humoral and cellular immune responses in RMD patients by reassuring the use of DMARD treatments during COVID-19. The study points to TNF-α inhibitors as those DMARDs permitting elicitation of functional antibodies to SARS-CoV-2 and adaptive effector populations available to counteract possible re-infections. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease, whose natural course has been deeply modified thanks to the development of new therapeutic approaches. The Janus kinase inhibitors (Jakinibs) represent the newest class of drugs introduced for treating RA. Among these, Filgotinib (FIL) has been developed as Janus kinase1 (JAK1) selective inhibitor, specifically targeting key pro-inflammatory mediators in RA pathogenesis. This narrative review provides an overview on FIL as new therapeutic approach for RA, with focus on its pharmacological properties, clinical efficacy, and safety profile. The following electronic databases were adopted for the study search: PubMed, Google Scholar, ClinicalTrials.gov and Abstract archive from the American College of Rheumatology and the European Alliance of Associations for Rheumatology. The phase II and phase III randomized controlled trials (RCTs) performed so far and their long-term extensions showed a comparable clinical efficacy of FIL to biologic treatments, with an acceptable safety profile. Thanks to these data, FIL was approved in Europe and Japan for the treatment of active RA, increasing the spectrum of therapeutic approaches and improving the possibility of a more tailored therapeutic strategy. Real-life data and head-to-head clinical trials will be needed to confirm its efficacy and safety. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID-19) pandemic raises a great challenge in the management of patients with rheumatoid arthritis (RA), which are generally more susceptible to infection events because of the autoimmune condition itself and the treatment with immunomodulatory drugs. The use of disease-modifying anti-rheumatic drugs (DMARDs), including biologics and targeted-synthetic DMARDs, has aroused particular interest because of both their immunosuppressive effects and their hypothetical potential in COVID-19 treatment. Areas covered: For this narrative review, a literature search was conducted between December 2019 and February 2021 on PubMed including epidemiological studies, gathering the main evidence available to date about the impact of COVID-19 on RA patients and the influence of anti-rheumatic drugs on patients' susceptibility to this infection. We also summarize the recommendations from the international guidelines on the management of rheumatic diseases and treatments in this pandemic context, especially focused on RA. Expert opinion: About a year after the outbreak of the pandemic, we are able to answer some of the most relevant questions regarding patients with RA and their management in this pandemic context. Our efforts must now be directed toward consolidating the currently available data with more rigorous studies and facing new issues and challenges including, foremost, vaccination. [ABSTRACT FROM AUTHOR]

Objective: To describe the incidence and severity of coronavirus disease 2019 (COVID‐19) in patients with rheumatic diseases treated with targeted synthetic or biologic disease‐modifying antirheumatic drugs (DMARDs) compared with that in the general population living in the same Italian region. Methods: Patients followed up at 2 rheumatology referral centers in Lombardy from February 25, 2020 to April 10, 2020 were invited to participate in a survey designed to identify patients who had confirmed COVID‐19, close contact with others with confirmed COVID‐19, or symptoms of the infection, and to detect changes in work, behavior, and disease management made in an attempt to prevent infection. The incidence of COVID‐19 in the Lombardy population was obtained from the National Institute of Statistics. COVID‐19 cases were confirmed by nasopharyngeal swab. Results: The survey was given to 955 patients (531 patients with rheumatoid arthritis, 203 patients with psoriatic arthritis, 181 patients with spondyloarthritis, and 40 patients with connective tissue diseases, vasculitides, or autoinflammatory diseases). These patients had a mean age of 53.7 years, and 67.4% were women. The rate of response to the survey was 98.05%, and the incidence of confirmed COVID‐19 cases was consistent with that in the general population (0.62% versus 0.66%; P = 0.92). None of the patients had severe complications or required intensive care treatment, and all of the patients who tested positive for COVID‐19 temporarily discontinued ongoing targeted synthetic drug or biologic DMARD therapy. Almost all patients took precautions to prevent the COVID‐19 infection (90.6%), and almost all continued treatment with targeted synthetic drugs or biologic DMARDs (93.2%). Disease activity remained stable in 89.5% of patients. Conclusion: Our results reflected the attitude of patients with rheumatic diseases regarding the prevention of the infection while maintaining their long‐term treatment regimens. The incidence and severity of COVID‐19 in patients treated with targeted synthetic drugs or biologic DMARDs was not significantly different from that in the general population in the same region. [ABSTRACT FROM AUTHOR]

On March 11th, 2020 the World Health Organization declared COVID-19 a global pandemic. The infection, transmitted by 2019 novel coronavirus (2019-nCov), was first discovered in December 2019, in Wuhan, Hubei Province, and then rapidly spread worldwide. Italy was early and severely involved, with a critical spread of the infection and a very high number of victims. Person-to-person spread mainly occurs via respiratory droplets and contact. The median incubation period is 5 days. The spectrum of respiratory symptoms may range from mild to severe, strictly depending on the age of the patient and the underlying comorbidities. In children COVID-19 related disease is less frequent and less aggressive. In Italy 1% of positive cases are under 18 years of age, and no deaths have been recorded before 29 years of age. For patients affected by rheumatic disease, despite the concerns related to the imbalance of their immune response and the effect of immunosuppressive treatments, there are still few data to understand the real consequences of this infection. Major scientific societies have issued recommendations to help rheumatologists in caring their patients. Interestingly, some of the drugs mostly used by rheumatologists appear to be promising in critical COVID-19 infected patients, where the hyperinflammation and cytokine storm seem to drive to the multiorgan failure. Pediatric rheumatologists are expected to play a supporting role in this new front of COVID-19 pandemic, both as general pediatricians treating infected children, and as rheumatologists taking care of their rheumatic patients, as well as offering their experience in the possible alternative use of immunomodulatory drugs. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease, which affects joints as well as extra-articular tissues. In the last decades, increasing targeted therapeutic options dramatically improved RA management by doubling the rate of patients achieving clinical remission. Currently, there is a need for management strategies aimed at limiting treatment-related adverse events and costs in good responders. Areas covered: Data on de-escalation of biologic drugs (especially for anti-TNF agents) are mainly available from post-hoc analyses of randomized controlled trials and from registry-based observational studies. This narrative review illustrates the rationales for dose tapering and expands to provide an overview of the efficacy of the different available strategies for reducing the exposure to biologic drugs in patients achieving a sustained clinical response. Selected studies are discussed as illustrative examples. Expert opinion: Withdrawal of biologic therapy might be attempted in limited patients with very early RA; conversely, established RA is more suitably managed with a progressive decrease of drug regimen, by either dose reduction or injection/infusion spacing. Further studies investigating potential factors predicting post-tapering disease relapse are warranted, in order to better identify the best candidates for a decreased-dose approach. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a systemic, autoimmune disease that affects joints and extra-articular structures. In the last decade, the management of this chronic disease has dramatically changed with the introduction of several targeted mechanisms of action, such as tumor necrosis factor-α inhibition, T-cell costimulation inhibition, B-cell depletion, interleukin-6 blockade, and Janus kinase inhibition. Beyond its well-known hematopoietic role on the proliferation and differentiation of myeloid cells, granulocyte-monocyte colony-stimulating factor (GM-CSF) is a proinflammatory mediator acting as a cytokine, with a proven pathogenetic role in autoimmune disorders such as RA. In vitro studies clearly demonstrated the effect of GM-CSF in the communication between resident tissue cells and activated macrophages at chronic inflammation sites, and confirmed the elevation of GM-CSF levels in inflamed synovial tissue of RA subjects compared with healthy controls. Moreover, a pivotal role of GM-CSF in the perception of pain has been clearly confirmed. Therefore, blockade of the GM-CSF pathway by monoclonal antibodies directed against the cytokine itself or its receptor has been investigated in refractory RA patients. Overall, the safety profile of GM-CSF inhibitors seems to be very favorable, with a particularly low incidence of infectious complications. The efficacy of this new mechanism of action is comparable with main competitors, even though the response rates reported in phase II randomized controlled trials (RCTs) appear to be numerically lower than the response rates observed with other biological disease-modifying antirheumatic drugs already licensed for RA. Mainly because of this reason, nowadays the development program of most GM-CSF blockers for RA has been discontinued, with the exception of otilimab, which is under evaluation in two phase III RCTs with a head-to head non-inferiority design against tofacitinib. These studies will likely be useful for better defining the potential role of GM-CSF inhibition in the therapeutic algorithm of RA. On the other hand, the potential role of GM-CSF blockade in the treatment of other rheumatic diseases is now under investigation. Phase II trials are ongoing with the aim of evaluating mavrilimumab for the treatment of giant cell arteritis, and namilumab for the treatment of spondyloarthritis. Moreover, GM-CSF inhibitors have been tested in osteoarthritis and diffuse subtype of systemic sclerosis. This review aims to describe in detail the available evidence on the GM-CSF blocking pathway in RA management, paving the way to a possible alternative treatment for RA patients. Novel insights regarding the potential use of GM-CSF blockers for alternative indications will be also addressed. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease more common in women than men (3:1). Although sex-based differences may play a complex role in promoting an autoimmune dysfunction, to date the comprehensive knowledge of the link between sex and RA is still partially lacking. Furthermore, males and females have been demonstrated to differently deal with their chronic pathologies, modifying the perceived sex-based burden of disease. Gender medicine is a newly approach focusing on the impact of gender differences on human physiology, pathophysiology, and clinical features of diseases, analyzing the complex interrelation and integration of sex and psychological and cultural behavior. A better comprehension of possible factors influencing sexual dimorphism in RA susceptibility, pattern of presentation, disease activity, and outcome could contribute to a tailored approach, in order to limit the morbidity of the disease. RA disease activity seems to be higher in women, whereas the response rate to synthetic and biologic disease-modifying therapies appears to be better in males. Moreover, the common strategies for RA management may be affected by concomitant pregnancy or childbearing desire, with particular regard to treatments with potential teratogenic effects or impact on fertility. Finally, comorbidities, such as fibromyalgia, major depression, and osteoporosis, are more frequent in females, while the impact of sex on cardiovascular risk is still controversial. Moving from the role of sex in influencing RA pathogenesis, epidemiology, and disease characteristics, this review explores the evidence on how sex can have an impact on strategies for managing patients with RA. [ABSTRACT FROM AUTHOR]

Introduction. To retrospectively evaluate the impact of comorbidities on treatment choice, 12-month clinical response, and 24-month retention rate in a cohort of patients with rheumatoid arthritis (RA) treated with a first-line tumor necrosis factor alpha inhibitor (TNFi), by using for the first time the Rheumatic Disease Comorbidity Index (RDCI). Methods. The study population was extracted from a local registry of RA patients receiving adalimumab or etanercept as first-line biologics between January 2001 and December 2013. The prevalence of comorbidities was computed, and patients were stratified according to RDCI for evaluating the role of comorbidities on TNFi choice, concomitant methotrexate, clinical response (1-year DAS28-ESR remission and low disease activity [LDA] and EULAR good-moderate response), and the 24-month retention rate. Results. 346 patients (172 adalimumab and 174 etanercept) were included. A significantly higher EULAR good/moderate response (P = 0.020) and DAS28-ESR remission (P = 0.003) were obtained according to RDCI (0, 1, 2, or ≥3). Lower RDCI (P = 0.022), male sex (P = 0.006), higher baseline DAS28-ESR (P = 0.001), ETN (P < 0.001), and concomitant methotrexate (P = 0.016) were predictors of EULAR good/moderate response. Elevated RDCI was a predictor of discontinuation of biologics (P = 0.036), whereas treatment with etanercept (P < 0.001) and methotrexate (P = 0.007) was associated with a lower risk of TNFi withdrawal. Conclusions. Multimorbidity, measured by RDCI, is a negative predictor of TNFi persistence on treatment and of achieving a good clinical response. The use of RDCI may be very useful for identifying patients with RA carrying those comorbid conditions associated with poor prognostic outcomes and for defining new treatment targets in multimorbid RA patients. [ABSTRACT FROM AUTHOR]

Abstract Objective The project aimed to collect expert consensus statements for the profiling of patients with axial spondyloarthritis (axSpA) candidate to biologic agents (bDMARDs) treatment, in order to better define the drivers for the best treatment choice. Methods The 6 more interesting topics about axSpA patient profiling were identified by the project steering committee and a panel of axSpA Italian experts. A systematic literature review (SLR) was performed for each of the selected topics according to the PICO format. Two rounds of a modified Delphi process were conducted. In the 1st round, the steering committee evaluated the results of the SLR in order to formulate statements for each topic. In the 2nd round, the experts panel discussed, rephrased when needed, and voted the level of agreement (on a 5-point Likert-type scale) for each statement. Consensus was defined as ≥66% agreement. Results The topics selected for the analysis were the differential efficacy of available bDMARDs on enthesitis/dactylitis, uveitis, radiographic progression and cardiovascular involvement, and the clinical response in non radiographic-axSpA and in patients receiving a second-line bDMARD. The Delphi rounds formulated 19 statements, all reaching the defined level of consensus in a second round including 25 rheumatologists highly skilled in the management of axSpA. Conclusion Identified consensus statements can help clinicians to apply to routine-care settings the results from clinical studies and international recommendations, providing a guide for individualization of treatment strategy in axSpA patients. [ABSTRACT FROM AUTHOR]

Spondyloarthropathies (SpA) encompass a group of chronic inflammatory diseases sharing common genetic and clinical features, including the association with HLA-B27 antigen, the involvement of both the axial and the peripheral skeleton, the presence of dactylitis, enthesitis, and typical extra-articular manifestations such as psoriasis, inflammatory bowel disease, and acute anterior uveitis (AAU). The latter is commonly reported as a noninfectious acute inflammation of the anterior uveal tract and its adjacent structures. AAU may affect more than 20% of SpA patients representing the most common extra-articular manifestation of the disease. Considering the potential consequences of untreated AAU, early diagnosis and aggressive treatment are crucial to avoid complications of remittent or chronic eye inflammation, such as visual loss and blindness. The management of SpA has dramatically improved over the last decades due to the development of new treat-to-target strategies and to the introduction of biologic disease modifying antirheumatic drugs (bDMARDs), particularly tumor necrosis factor alpha inhibitors (TNFis), currently used for the treatment of nonresponder patients to conventional synthetic agents. Along with the improvement of musculoskeletal features of SpA, bDMARDs provided an additional effect also in the management of AAU in those patients who are failures to topical and systemic conventional therapies. Nowadays, five TNFis, one interleukin-17, and one interleukin 12/23 blocker are licensed for the treatment of SpA, with different proven efficacy in preventing and treating ocular involvement. The aim of this review is to summarize the current options and to analyze the future perspectives for the management of SpA-associated AAU. [ABSTRACT FROM AUTHOR]

Objective To establish evidence-based and experts' opinion filtered statements on the optimal treatment choice between cycling (switch) and changing mode of action strategies (swap) in RA patients failing TNF inhibitors (TNFis). Methods The relevant question (switch vs swap) was rephrased into a research question according to the population, intervention, comparison and outcome (PICO) strategy, considering all the available scientific evidence published from the 2013 EULAR set of recommendations up to mid-January 2016. Final statements derived from the retrieved scientific evidence and experts' consensus, with eventual rephrasing through a Delphi method during a national consensus of Italian rheumatologists. Results From a total of 365 records, 12 studies were finally included. The final statements argued that, until head-to-head comparison data are available, switch and swap can be still considered suitable strategies in RA patients failing first TNFi, even though some data seem to lend more support to a different mode of action-targeted strategy. Conclusion After failure of first TNFi course, switch and swap can be currently considered as alternative suitable approaches in RA patients. [ABSTRACT FROM AUTHOR]

Background: Treat to target (T2T), aiming at inactive disease (ID), has become the recommended strategy for axial-SpA (ax-SpA). Using the Ankylosing Spondylitis Disease Activity Score (ASDAS), we assessed the prevalence of ID in ax-SpA patients treated with TNFa inhibitors (TNFi). Methods: A multicentric, cross-sectional study was performed assessing disease activity status (BASDAI and ASDAS) of consecutive patients with ax-SpA on stable treatment with TNFi for at least six months. We analyzed differences with nonradiographic axSpA (nr-ax-SpA) and the influence of population characteristics and comorbidities in reaching ID. ID was defined as ASDAS-CRP <1.3. Results: A total of 218 patients were enrolled, 165 with AS and 53 with nr-ax-SpA. ASDAS-CRP ID was reached by 89 (40.8%) patients, while 163 (74.8%) of patients achieved good disease control with BASDAI. There were no significant differences between the two diagnostic groups. Multivariate logistic regression demonstrated a negative correlation of concomitant fibromyalgia, higher BASMI and current NSAIDs with the chances of reaching ASDAS-CRP ID or BASDAI <4. Conclusion: T2T represents a new challenge in the management of ax-SpA, with recently introduced disease activity measures being significantly more stringent. The prevalence of ID was affected by concomitant fibromyalgia, decreased spine mobility and concomitant NSAIDs. [ABSTRACT FROM AUTHOR]

The introduction of biologic disease–modifying anti-rheumatic drugs (bDMARDs) has dramatically changed the management of rheumatoid arthritis (RA). However, in a real-life setting about 30–40% of bDMARD treated patients experience drug discontinuation because of either inefficacy or adverse events. According to international recommendations, to date the best strategy for managing first-line bDMARD failures has not been defined yet and available data (especially on TNF inhibitors [TNFis]) seem to drive toward a personalized approach for the individual patient. Some TNFi partial responders may benefit from optimization of concomitant methotrexate therapy or from switching to a different concomitant sDMARD such as leflunomide. Conversely, apart from infliximab, TNFi dose escalation seems to be poor efficacious and poor cost-effective compared with alternative strategies. Albeit counterintuitive, the use of a second TNFi after the failure of the first-one (cycling strategy) is supported by clear evidences and has become widespread in the 2000s as the result of the limited alternative options till the introduction of bDMARDs with a mechanism of action other than TNF blockade. Nowadays, the use of abatacept, rituximab, tocilizumab, or JAK inhibitors as second-line agent (swapping strategy) is strongly supported by RCTs and real-life experiences. In the absence of head-to-head trials directly comparing these two strategies, meta-analyses of separated RCTs failed to find significant differences in favor of one or another choice. However, results from most observational studies, including well designed prospective pragmatic randomised analyses, demonstrated the superiority of swapping over cycling approach, whereas only few studies reported a comparable effectiveness. In this review, we aimed to critically analyze all the potential therapeutic options for the treatment of first-line bDMARD failures in order to provide a comprehensive overview of available strategies to be applied in clinical practice. [ABSTRACT FROM AUTHOR]

Objective To evaluate the 8-year survival of the first tumor necrosis factor inhibitor (TNFi) in patients with axial spondyloarthritis (SpA) or psoriatic arthritis (PsA), identify the predictive factors for withdrawal, and compare the discontinuation rates for infliximab, etanercept, and adalimumab. Methods We evaluated PsA and axial SpA patients treated with a first-line TNFi between 2005 and 2015 at 4 Italian tertiary centers. Eight-year drug survival was calculated by the Kaplan-Meier method, and risk for discontinuation among treatment groups compared by stratified log-rank test. Univariate and multivariate Cox proportional hazard models were developed to examine predictors of withdrawal. Results Of 614 patients (316 axial with SpA, 298 with PsA), 203 received adalimumab, 131 etanercept, and 280 infliximab, with similar frequencies in axial SpA and PsA subgroups. The cumulative 8-year retention rate in the whole population was 55.1% (57.2% and 51.9% for axial SpA and PsA, respectively; P = not significant). No significant differences were observed in drug persistence among individual TNFi in either group. Male sex (hazard ratio [HR] 0.595 [95% confidence interval (95% CI) 0.405-0.875]; P = 0.008) and concomitant methotrexate use (HR 0.648 [95% CI 0.426-0.985]; P = 0.042) were associated with a lower risk of withdrawal in PsA. High baseline Bath Ankylosing Spondylitis Disease Activity Index (HR 0.9842 [95% CI 0.9708-0.9980]; P = 0.028) was associated with a lower risk of withdrawal in axial SpA. No difference was found in the comparative analysis of reasons for discontinuation between PsA and axial SpA. Conclusion We reported that the real-life 8-year retention rate of the first TNFi in axial SpA and PsA is greater than 50%, with no significant differences between axial SpA and PsA, irrespective of the individual TNFi. [ABSTRACT FROM AUTHOR]