The real-world use of different anti-tumor necrosis factor agents in a Northern European population of patients with Behçet's disease.

OBJECTIVE: The aim of this study was to evaluate prescription practices, treatment responses, and serious adverse events of anti-tumor necrosis factor (anti-TNF) therapies in Behçet's disease (BD). MATERIAL AND METHODS: Patients with BD satisfying the International Study Group for Behçet's Disease or the International Criteria for Behçet's Disease criteria were recruited from a regional rheumatology program. The choice of anti-TNF, treatment response, and adverse events were specified. Response to treatment was evaluated by the detection of new, worsening, or improving clinical features, and management was benchmarked against current The European League against Rheumatism recommendations published in 2008. RESULTS: Out of the total of 22 patients, 18 (81.9%) received anti-TNF therapies, resulting in 14 (77.8%) complete and 4 (22.2%) partial remissions. Eleven (61.1%) patients switched to a second anti-TNF, seven patients (38.9%) required three different anti-TNFs, and one required a fourth anti-TNF to achieve remission. Two patients required retrials before their disease was controlled. Anti-TNF therapy included infliximab (IFX): n=15, 83.3%; adalimumab (ADA): n=9, 50%; golimumab: n=6, 33.3%; etanercept: n=5, 27.8%; and certolizumab pegol: n=2, 11.1%. Secondary failure was observed with IFX (4/15; 26.7%) and ADA (2/9; 22.2%), and these (100%) were manifested after at least 2 years of treatment. Five patients with potentially life-threatening laryngeal involvement received anti-TNFs successfully halting disease progression. Five allergic reactions were encountered, and five serious infections were documented involving three patients aged ≥ 50 years, all with the use of IFX. CONCLUSION: Anti-TNF therapy induced a clinical response in 100% patients and achieved complete remission in 78% patients. It provides an effective alternative option for first-line therapy in severe BD where many conventional immunosuppressive therapies fail. Patients with BD who do not respond to one or more anti-TNFs because of intolerance, ineffectiveness, or secondary failure might benefit from switching to another drug from this group or even a retrial of a previously administered anti-TNF because unsatisfactory results with one biologic is not predictive of response to another anti-TNF. For those with potentially life-threatening destructive laryngeal manifestation, anti-TNF as a first choice may be considered.

Early- and late-stage morphea subtypes with deep tissue involvement is treatable with Abatacept (Orencia).

OBJECTIVES: This case series explores the potential efficacy of Abatacept in patients presenting with morphea subtypes and deep tissue involvement. METHODS: Three patients with established morphea subtypes and deep tissue involvement and with no contraindication to Abatacept were included in this prospective open-label study. The index patient was exceptionally severely affected with a mean Modified Rodnan Skin Score (MRSS) of 38/51. At baseline, whole-body MRI and skin biopsy were performed which confirmed classical deposition of dense fibrous tissue in the appropriate layer of the skin. MRSS was performed independently by three clinicians and VAS scores (10cm) were measured at baseline for Patient Global Disease Activity (PGDA), Patient Global Pain (PGP), Patient Day Pain (PDP), Patient Night Pain (PNP), and Physician Global Disease Activity (PhGDA). Patients 2 and 3 were similarly screened at baseline except for MRI. Patients were commenced on Abatacept as per body weight (10mg/kg) given intravenously with concomitant tapering dose of oral prednisolone. All three were re-assessed at 6 months and the index case was further re-assessed at 18 months. RESULTS: All patients tolerated the Abatacept well and showed dramatic improvement. The index patient's clinical signs and symptoms, whole-body MRI, and mean Modified Rodnan Skin Score improved dramatically from baseline by 37% at 6 months and by 74% at 18 months. There were no clinically significant adverse outcomes noted. CONCLUSION: We present three cases, one with exceptionally severe disease, which demonstrated excellent clinical response to Abatacept. Abatacept is a promising option for the treatment of severe or resistant morphea, especially in those with deep tissue involvement.

Significant laryngeal destruction in a northern European cohort of Behçet's disease patients.

OBJECTIVES: Behçet's disease (BD) is a multisystem autoimmune disease of unknown origin typically affecting the triad of oral and genital mucosa and the eye. Limited data are available in the literature regarding the otolaryngology-related manifestations of BD, particularly in northern Europeans. This is a novel study detailing surprising and significant laryngeal structural changes in a northern European cohort of BD. METHODS: Patients meeting the International Study Group for Behçet's Disease (ISGBD) and the International Criteria for Behçet's Disease (ICBD) criteria for diagnosis were identified from an institutional database. Patients underwent examination with an otolaryngologist, including flexible laryngoscopy. Intra-oral, pharyngeal and laryngeal manifestations of BD were documented and characterised. Patients underwent hearing assessment with pure-tone audiometry. RESULTS: Fifteen patients with BD were identified (4 male, 11 female; median age 36 years). 60% (n=9) showed evidence of disease on examination and flexible laryngoscopy. 33% (n=5) showed laryngeal changes related to BD. 13% (n=2) demonstrated bilateral sensorineural hearing loss. The 5 cases demonstrating laryngeal manifestations of disease are described in detail with photographic records. CONCLUSIONS: Limited data has been published regarding the laryngeal manifestations of BD, particularly in a northern European population. Our cohort of BD patients demonstrate significant laryngeal structural changes. It would appear that these clinically relevant changes may be more common than was previously thought. Raised awareness of the risk of laryngeal pathology in BD patients, often in the absence of overt clinical symptomatology, may result in earlier diagnosis and treatment. Rheumatologists and otolaryngologists should consider closer multi-disciplinary co-operation in the management and follow up of patients with BD.

Impact of outpatient clinic ultrasound imaging in the diagnosis and treatment for shoulder impingement: a randomized prospective study.

The use of musculoskeletal ultrasonography (MSUS) in guiding subdeltoid injection has been shown to improve outcome up to 6 weeks in a few small studies. A recent meta-analysis identified the need for further studies with longer-term outcome and larger sample size. This randomized prospective study assessed whether clinic-based MSUS can significantly improve diagnostic accuracy in shoulder pain and whether MSUS-guided shoulder injection results in improved long-term outcomes. One hundred consecutive patients with 125 painful shoulders were recruited. Patients were randomized to receive either sonographic assessment with consequent palpation-guided injection (Group 1, n = 66) or sonographic assessment with a MSUS-guided injection of 40 mg of methylprednisolone acetate (Group 2, n = 59). A blinded rheumatologist (ADF) performed clinical assessments at baseline, 6 and 12 weeks including shoulder function tests (SFTs) (Hawkins-Kennedy test, supraspinatus tendon tenderness), physician global assessment (PGA) and patient visual analogue scores (VAS) for pain (0-10). Eighty patients with 90 symptomatic shoulders completed 12-week follow-up. Twenty patients, 11 (20 shoulders) from the palpation-guided group and 9 (15 shoulders) from the MSUS-guided group, were excluded at 6 weeks either due to requirement for repeat injection or due to surgical referral. Mean age for patients was 57.7 years, and 65 % patients were female; mean shoulder pain duration was 18 weeks (range 14-22 weeks). SFTs, patient VAS and PGA scores for pain improved significantly from baseline in both groups with significantly greater improvements in the MSUS-guided group (44 shoulders) compared to the palpation-guided group (46 shoulders) in all parameters at 6 (p < 0.01) and 12 weeks (p < 0.05). The use of MSUS in guiding subdeltoid injection has been shown to improve outcome up to 6 weeks in a few small studies. A recent meta-analysis identified the need for further studies with longer-term outcome and larger sample size.

Ankylosing spondylitis in Ireland: patient access and response to TNF-α blockers.

To investigate a group of Irish ankylosing spondylitis patients: current prescription practice for TNF blockers and patient response. All patients presenting with ankylosing spondylitis (AS) and treated with TNF-alpha between January 2006 and 2008 in the midwestern region of Ireland were studied. Response was evaluated using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and CRP results at 6 months. A total of 47 AS patients (32 men: 15 women, mean age 37.7 years, median disease duration 20 years, 80% HLA B27 positive) were identified; 66% were on disease-modifying anti-rheumatic drugs (DMARDs) concomitantly. All patients satisfied BSR/ASAS disease severity criteria for TNF-alpha at baseline, and mean BASDAI was 6.2, BASFI 6.9, and CRP 27.5 mg/L. At 6 months, these had reduced to a mean BASDAI of 3.8, BASFI 4.6, and CRP of 8.9 mg/L. Patients with advanced AS (disease duration >10 years, mean BASFI 7.5) responded at least as well. No allergies or serious side effects were encountered, and one patient successfully switched TNF agent due to secondary failure. Initial good responses at 6 months were seen to be maintained in sub-group analysis at 12 months. Disease severity in patients gaining access to treatment for active AS with TNF blockers in Ireland is very high. Patients mainly satisfy international guidelines for the use of biologics (BSR, EULAR) with some minor exceptions. High disease activity and long disease duration may predict better treatment response. Response rates were good and treatment was well tolerated, and no differences in response were noted between the 3 agents employed.