The study aim was to evaluate the efficacy of adalimumab (ADA) in a large series of Behçet’s disease (BD)-related uveitis. We performed a multicenter retrospective observational study including 40 ...selected patients (66 eyes) receiving ADA. Clinical data were retrospectively analyzed at baseline, at 3 and 12 months of treatment. Primary end point was reduction of ocular inflammatory flares. Secondary end points were improvement of best corrected visual acuity (BCVA), reduction of macular thickness measured by optical coherence tomography (OCT), reduction in the occurrence of vasculitis assessed by fluorescein angiography (FA), and evaluation of statistically significant differences between patients treated with ADA monotherapy and those undergoing ADA plus DMARDs and in patients firstly treated with ADA compared to patients previously administered with other biologics; ADA steroid sparing effect was also evaluated. During the first 12 months of ADA therapy, the number of flares significantly decreased from 200 flares/100 patients/year to 8.5 flares/100 patients/year (
p
< 0.0001). Similarly, BCVA improved if compared to baseline (7.4 ± 2.9 versus 8.5 ± 2.1,
p
= 0.03). OCT findings significantly improved showing a mean reduction of central macular thickness (CMT) of 27.27 ± 42.8 μm at the end of follow-up (
p
< 0.006). FA identified retinal vasculitis in 22 cases at baseline (55%), 8 (20%) cases after 3 months, and in only one (2.5%) case at 12-month follow-up. FA improvement was highly significant at 3- and 12-month follow-up if compared to baseline (
p
< 0.0001 and
p =
0.006, respectively). ADA is highly effective and safe for the treatment of BD-related uveitis, providing a long-term control of ocular inflammation.
Abstract Behçet's disease (BD) is a multi-systemic disorder of unknown etiology characterized by relapsing oral–genital ulcers, uveitis, and involvement of the articular, gastrointestinal, ...neurologic, and vascular systems. Although the primum movens of this condition remains unknown, a tangled plot combining autoimmune and autoinflammatory pathways has been hypothesized to explain its start and recurrence. In-depth analysis of BD pathogenetic mechanisms, involving dysfunction of multiple proinflammatory molecules, has opened new modalities of treatment: different agents targeting interleukin-1 have been studied in recent years to manage the most difficult and multi-resistant cases of BD. Growing experience with anakinra, canakinumab and gevokizumab is discussed in this review, highlighting the relative efficacy of each drug upon the protean BD clinical manifestations. Safety and tolerability of interleukin-1 antagonists in different doses have been confirmed by numerous observational studies on both large and small cohorts of patients with BD. In particular, the potential for Mycobacterium tuberculosis reactivation and tuberculosis development appears to be significantly lower with interleukin-1 blockers compared to tumor necrosis factor-α inhibitors, thus increasing the beneficial profile of this approach.
Recommendations related to ocular, mucosal and cutaneous involvement of Behçet's disease (BD) are mainly evidence-based, but in cases of vascular, neurological and gastrointestinal involvement there ...are no guidelines to define the best treatment strategy. We report three adult patients with BD, who received an interleukin-1β inhibitor by subcutaneous injections, canakinumab (at the dosage of 150 mg every 6 weeks), after failure shown by corticosteroids and different combinations of immunosuppressant agents. The prompt and sustained clinical efficacy demonstrated by canakinumab as a monotherapy supports the opportunity of using this specific anti-interleukin-1β agent as a valid therapeutic option for resistant or refractory BD. Open trials and observational studies should be performed to test canakinumab efficacy on a larger number of patients. The most appropriate dosage and intervals between administrations should be decided according to the individual patient, severity or recurrence of clinical manifestations and major organ involvement.
The primary aim of the study was to evaluate the efficacy of tumor necrosis factor (TNF)-α blockers adalimumab (ADA) and infliximab (IFX) in refractory sight-threatening retinal vasculitis (RV) ...during a 12-month follow-up period. Secondary aims were to evaluate (i) any impact of concomitant conventional disease-modifying anti-rheumatic drugs (cDMARDs) and different lines of biologic therapy; (ii) any difference in terms of efficacy between ADA and IFX; (iii) consequences of biotherapies on the best-corrected visual acuity (BCVA); (iv) corticosteroid-sparing effect; and (vi) ocular complications during anti-TNF-α treatment. Demographic, clinical, and therapeutic data were retrospectively collected from the medical records and statistically analyzed. Forty-eight patients (82 eyes) were recruited, 22 (45.8%) of which received IFX and 26 (54.2%) ADA. The percentages of patients achieving RV remission within 3 and 12 months were 54 and 86%, respectively. A significant decrease in RV detection was identified from baseline to 3-month (
p
< 0.0001) and 12-month (
p
< 0.0001) assessments and between 3-month and 12-month visits (
p
= 0.004). No differences were identified in terms of RV resolution between (i) patients undergoing monotherapy and those co-administered with cDMARDs at 3-month (
p
= 0.560) and 12-month (
p
= 0.611) follow-up; (ii) biologic-naïve patients and those already exposed to other biologics at 3-month (
p
= 0.497) and 12-month (
p
> 0.99) visits; and (iii) patients treated with ADA and those treated with IFX (
p
= 0.357). During the study period, a statistically significant corticosteroid-sparing effect was observed (
p
= 0.0002), while BCVA values did not significantly change (
p
= 0.950). Anti-TNF-α monoclonal antibodies have proved excellent results in patients with recalcitrant sight-threatening RV.
Several pathogenetic studies have paved the way for a newer more rational therapeutic approach to non-infectious uveitis, and treatment of different forms of immune-driven uveitis has drastically ...evolved in recent years after the advent of biotechnological drugs. Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis. Nevertheless, the decision-making process turns out to be extremely difficult in anti-tumor necrosis factor or multidrug-resistant cases. Interleukin (IL)-6 holds a critical role in the pathogenic pathways of uveitis, due to its extended and protean range of effects. On this background, manipulation of IL-6 inflammatory cascade has unraveled encouraging outcomes. For instance, rising evidence has been achieved regarding the successful use of tocilizumab, the humanized monoclonal antibody targeted against the IL-6 receptor, in treating uveitis related to juvenile idiopathic arthritis or Behçet’s disease. Similar findings have also been reported for uveitis associated with systemic disorders, such as rheumatoid arthritis or multicentric Castleman disease, but also for idiopathic uveitis, the rare birdshot chorioretinopathy, and even in cases complicated by macular edema. This work provides a digest of all current experiences and evidences concerning IL-6 blockade, as suggested by the medical literature, proving its potential role in the management of non-infectious uveitis.
Behçet’s disease (BD) is a multisystemic disorder of unknown etiology mainly defined by recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis, all of which represent the ...“stigmata” of disease. However, many other organs including the vascular, neurological, musculoskeletal, and gastrointestinal systems can be affected. The gastrointestinal involvement in Behçet’s disease (GIBD), along with the neurological and vascular ones, represents the most feared clinical manifestation of BD and shares many symptoms with inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis. Consequently, the differential diagnosis is often a daunting task, albeit the presence of typical endoscopic and pathologic findings may be a valuable aid to the exact diagnosis. To date, there are no standardized medical treatments for GIBD; therefore therapy should be tailored to the single patient and based on the severity of the clinical features and their complications. This work provides a digest of all current experience and evidence about pharmacological agents suggested by the medical literature as having a potential role for managing the dreadful features of GIBD.
Abstract Background: Optic perineuritis is a rare form of orbital inflammatory pseudotumor in which the specific target tissue is the optic nerve sheath. Patients are mainly represented by adult ...women. Differential diagnosis with demyelinating optic neuritis is essential in terms of prognosis and treatment. Case presentation: An 8-year-old Caucasian girl presented with bilateral loss of vision, disc edema, eye movement impairment, and diplopia. Brain MRI findings were suggestive of optic perineuritis. The patient received steroid pulse therapy followed by prolonged course of oral steroid therapy. The visual acuity recovered dramatically within 2 days. Two months later, a new MRI investigation was normal. No clinical relapse was observed at the follow-up. Discussion: We first report on a child affected by optic perineuritis. Our observation suggests that optic perineurits should be considered in the differential diagnosis of children presenting with visual loss and disc edema. An early and correct diagnosis may lead to an appropriate therapeutic approach with very good outcome.
This study aimed to evaluate the role of interleukin (IL)-1 inhibitors anakinra (ANA) and canakinumab (CAN) in the treatment of Behçet’s disease (BD)-related uveitis. Multicenter retrospective ...observational study includes 19 consecutive BD patients (31 affected eyes) received treatment with anti-IL-1 agents. Data were analyzed at baseline and at 3 and 12 months. The primary endpoint is the reduction of ocular inflammatory flares (OIF). The secondary endpoints are improvement of best corrected visual acuity (BCVA); reduction of macular thickness defined by optical coherence tomography (OCT) and of vasculitis identified with fluorescein angiography (FA); evaluation of statistically significant differences between patients treated with IL-1 inhibitors as monotherapy, subjects also administered with disease modifying anti-rheumatic drugs (DMARDs) and/or corticosteroids as well as between patients administered with IL-1 inhibitors as first line biologic treatment and those previously treated with TNF-α inhibitors. At 12 months, OIF significantly decreased from 200 episodes/100 patients/year to 48.87 episodes/100 patients/year (
p
< 0.0001). The frequency of retinal vasculitis identified by FA significantly decreased between baseline and 3- and 12-month follow-up visits (
p
< 0.0001 and
p
= 0.001, respectively). OIF rate was significantly higher in patients co-administered with DMARDs (81.8 episodes/100 patients/year) than in patients undergoing IL-1 inhibitors as monotherapy (0.0 episodes/100 patients/year) (
p
= 0.03). No differences were identified on the basis of corticosteroid use and between patients administered with IL-1 inhibitors as first line biologic approach or second line. Steroid dosage was significantly decreased at 12-month visit compared to baseline (
p
= 0.02). Treatment with IL-1 inhibitors is effective in the management of BD-related uveitis and provides a long-term control of ocular inflammation in refractory and long-lasting cases.
The study objective was to report treatment with an interleukin (IL)-1 receptor antagonist, anakinra, in patients with multiorgan Behcet's disease (BD). Comparison of clinical manifestations, ...previous treatments, markers of inflammation, concomitant medications, treatment regimen modifications, relapses, and adverse events before and during anakinra administration among patients with BD were evaluated. Nine BD patients (mean age 34.55 ± 16.30 years) refractory to tumor necrosis factor blockers and standardized therapies are reported in our survey. Their mean age at disease onset was 25 ± 13.88 years and their overall disease duration was 9.55 ± 5.33 years. All patients were positive for the HLA-B51 allele. Within 1 or 2 weeks following the initiation of anakinra, eight out of nine patients promptly responded, and most of them were maintained on 100 mg of daily anakinra with low doses of prednisone. However, most patients experienced a relapse in one or more clinical manifestations over time (mean time to relapse 29 ± 21.65 weeks), and only one patient remained completely under control on anakinra monotherapy. Despite a relapse in one or more disease manifestations, treatment was continued in most patients for a mean period of 13.75 ± 6.49 months. No serious adverse events occurred. Eight out of nine refractory BD patients showed a prompt improvement after starting anakinra, supporting the concept that IL-1 plays a pathological role in this disease. Nevertheless, after several months, most patients experienced a relapse. It remains unclear whether increasing the dose of anakinra would have prevented the reoccurrence of disease activity.
Adalimumab (ADA) has been shown to be an effective treatment for Behçet's disease (BD)-related uveitis. We aimed at evaluating the cumulative retention rate of ADA during a 48-month follow-up period ...in patients with BD-related uveitis, the impact of a concomitant use of disease modifying anti-rheumatic drugs (DMARDs) on ADA retention rate, and differences according to the various lines of biologic therapy (ie, first- vs second-line or more). Predictive factors of response to ADA were also investigated.
We enrolled patients diagnosed with BD-related uveitis and treated with ADA between January 2009 and December 2016. Cumulative survival rates were studied using the Kaplan-Meier plot, while the log-rank (Mantel-Cox) test was used to compare survival curves. Statistical analysis was performed to identify differences according to the response to ADA.
54 consecutive patients (82 eyes) were eligible for analysis. The drug retention rate at 12- and 48-month follow-up was 76.9% and 63.5%, respectively. No statistically significant differences were identified according to the use of concomitant DMARDs (p=0.27) and to the different lines of ADA treatment (p=0.37). No significant differences were found between patients continuing and discontinuing ADA in terms of age (p=0.24), age at BD onset (p=0.81), age at uveitis onset (p=0.56), overall BD duration (p=0.055), uveitis duration (p=0.46), human leucocyte antigen-B51 positivity (p=0.51), and gender (p=0.47).
ADA retention rate in BD-related uveitis is excellent and is not affected by the concomitant use of DMARDs or by the different lines of biological therapy. Negative prognostic factors for BD uveitis do not impact ADA efficacy.
PDF
