The main outcomes of the therapies for rheumatoid arthritis (RA) must be preventing, or at least lessening, the development of structural damage. Biological disease-modifying anti-rheumatic drugs ...(bDMARDs), targeting tumour necrosis factor-α (TNF-α) or other key steps (IL-1, IL-6, T cells, B cells) in the pathogenesis of RA, have given clues to be effective and safe as treatments for RA, being capable of improving disease activity, ameliorating functional ability and halting joint damage. A large body of evidence, stemming from randomized clinical trials, observational studies, and registries, has shown that the beneficial effects of the bDMARDs become optimal when combined with synthetic (s)-DMARDs, mainly methotrexate (MTX). Despite combination therapy is advocated by the international guidelines for the management of RA, data from the daily standard of care indicate that almost one third of RA patients are treated with bDMARDs as monotherapy. Many reasons may be taken into account to explain this gap from official recommendations, among which the fact that in real-life settings, the assessment of clinical outcomes is exclusively based on clinical indices, disregarding the evolution of bone damage. Furthermore, some bDMARDs have been launched in the market with the official approval to be used as monotherapy. But even for the latter, there is no conclusive proof that monotherapy regimen is comparable to co-therapy with MTX in preventing articular damage. In conclusion, the most recent published data show that combination therapy with bDMARDs and MTX represents the best therapeutic option for the treatment of RA since it can stop or at least slow the progression of disabling structural damage.
Behçet’s disease (BD) is a multisystemic disorder of unknown etiology characterized by the “triple symptom complex” consisting of recurrent oral aphthosis, genital ulcers, and chronic relapsing ...bilateral uveitis. Recurrent mucocutaneous lesions are generally considered the hallmark of the disease, being the most common symptoms presenting at the onset of disease. Although the improvement of knowledge about the pathogenetic mechanism added important changes in the treatment management of BD clinical manifestations, thus avoiding the appearance of serious life-threatening complications which are disease related, the mucocutaneous lesions are still the most nagging clinical manifestations to be treated. In this work we reviewed the current state of knowledge regarding the therapeutic approaches for mucocutaneous lesions of BD mainly based on controlled studies to provide a rational framework for selecting the appropriate therapy for treating these troublesome features of the disease.
Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis.
To perform a ...nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults.
We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016.
Five hundred and twenty-six treatment courses given to 475 patients (195 males, 280 females; 111 children and 364 adults) were evaluated. ANA was administered in 421 (80.04%) courses, CAN in 105 (19.96%). Sixty-two (32.1%) patients had been treated with both agents. IL-1 inhibitors were employed in 38 different indications (37 with ANA, 16 with CAN). Off-label use was more frequent for ANA than CAN (p < 0.0001). ANA was employed as first-line biologic approach in 323 (76.7%) cases, while CAN in 37 cases (35.2%). IL-1 inhibitors were associated with corticosteroids in 285 (54.18%) courses and disease modifying anti-rheumatic drugs (DMARDs) in 156 (29.65%). ANA dosage ranged from 30 to 200 mg/day (or 1.0-2.0 mg/kg/day) among adults and 2-4 mg/kg/day among children; regarding CAN, the most frequently used posologies were 150mg every 8 weeks, 150mg every 4 weeks and 150mg every 6 weeks. The frequency of failure was higher among patients treated with ANA at a dosage of 100 mg/day than those treated with 2 mg/kg/day (p = 0.03). Seventy-six patients (14.4%) reported an adverse event (AE) and 10 (1.9%) a severe AE. AEs occurred more frequently after the age of 65 compared to both children and patients aged between 16 and 65 (p = 0.003 and p = 0.03, respectively).
IL-1 inhibitors are mostly used off-label, especially ANA, during adulthood. The high frequency of good clinical responses suggests that IL-1 inhibitors are used with awareness of pathogenetic mechanisms; adult healthcare physicians generally employ standard dosages, while pediatricians are more prone in using a weight-based posology. Dose adjustments and switching between different agents showed to be effective treatment strategies. Our data confirm the good safety profile of IL-1 inhibitors.
Our aim was to retrospectively assess the role of golimumab as a treatment choice in patients with Behçet’s disease (BD). Seventeen patients diagnosed with BD according to the international criteria ...were consecutively enrolled; the BD Current Activity Form (BDCAF) was used to evaluate disease activity. After having collected clinical data from patients, statistical analysis was performed to identify differences between the start of therapy and last visit; significance was defined as
p
< 0.05. The mean duration of golimumab treatment was 18.47 ± 20.8 months. At the time of data enrollment, 12/17 (70.6%) patients were still on golimumab therapy. The mean time required to obtained clinical response was 4.9 ± 5.7 weeks. At 3 months evaluation, golimumab was able to control BD-related manifestations in 16/17 (94.1%) cases; the BDCAF values were significantly decreased at the last follow-up compared to those assessed at the start of golimumab (
p
= 0.002). The BDCAF improvement was significantly higher among patients co-administered with DMARDs than those undergoing golimumab as monotherapy (
p
= 0.048). At the last follow-up visit, corticosteroids had been discontinued in 10 (58.8%) patients, while the corticosteroid dosage was significantly lower at the last follow-up visit compared to the start of therapy in those patients already on corticosteroids at the end of the study (
p
= 0.001). Golimumab is a promising and safe treatment opportunity in BD patients with different systemic involvement, inducing a prompt resolution of clinical manifestations, a meaningful improvement of BDCAF score, and a significant corticosteroid-sparing effect. However, golimumab co-administered with DMARDs has provided better results than in patients undergoing monotherapy.
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.
The aim of the study was to retrospectively evaluate the long-term safety profile of anti-tumour necrosis factor (TNF)-α agents on the liver of patients with spondyloarthritis (SpA) and a previously ...resolved hepatitis B virus (HBV) infection.
Medical records from 992 consecutive outpatients receiving anti-TNF-α therapy between 2007 and 2015 were retrospectively reviewed. HBV infection was assessed evaluating HBV surface antigen (HBsAg), antibodies to HBsAg (anti-HBs), antibodies to hepatitis B core (anti-HBc), and HBV-DNA levels. In patients with a previously resolved HBV infection, serum levels of aminotransferase (AST/ALT) were also assessed every three months, while HBsAg and HBV-DNA every six months.
We identified 131 consecutive patients (70 males, 61 females) with SpA and resolved HBV infection. At baseline none of the patients were positive for HBV-DNA, and AST/ALT levels were within the normal range with no subsequent increase during the observational treatment period. None received antiviral therapy prior to or during anti-TNF drug administration. At the end of the follow-up period (75.50±33.37 months) no viral reactivation was observed in anti-HBc positive patients, regardless of anti-HBs positivity. During the whole follow-up, HBV-DNA was undetectable in all patients, HBsAg remained negative, and it was not necessary to discontinue biologic therapy because of liver damage.
Our results confirm that pre-emptive antiviral prophylaxis may not be necessary routine, but strict monitoring for AST/ALT levels, as well as for changes in HBV serology and HBV-DNA remain necessary and seem a realistic and cost-effective approach to identify early viral reactivation.
The innate immune system is involved in the pathophysiology of systemic autoinflammatory diseases (SAIDs), an enlarging group of disorders caused by dysregulated production of proinflammatory ...cytokines, such as interleukin-1β and tumor necrosis factor-α, in which autoreactive T-lymphocytes and autoantibodies are indeed absent. A widely deranged innate immunity leads to overactivity of proinflammatory cytokines and subsequent multisite inflammatory symptoms depicting various conditions, such as hereditary periodic fevers, granulomatous disorders, and pyogenic diseases, collectively described in this review. Further research should enhance our understanding of the genetics behind SAIDs, unearth triggers of inflammatory attacks, and result in improvement for their diagnosis and treatment.
We report on a patient with a long-standing history of recurrent oral aphthosis and pseudofolliculitis, diagnosed with Behçet’s disease (BD), previously treated with high-dose prednisone, colchicine, ...cyclosporine, cyclophosphamide and methotrexate, all of which were partially effective. Treatment with the chimeric mouse-human anti-tumour necrosis factor (TNF)-α monoclonal antibody infliximab brought about the resolution of mucocutaneous lesions for a period of 6 years. After an oral and articular BD relapse, the anti-interleukin-6 agent tocilizumab was started in association with high-dose prednisone. Unexpectedly, the patient experienced a paradoxical mucocutaneous flare following tocilizumab administration, which worsened after the second infusion. Tocilizumab was then discontinued, and total recovery was achieved after the patient was started on the fully human anti-TNF-α monoclonal antibody golimumab in association with colchicine and methylprednisolone.
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