Christopher Banse

Reactive macrophage activation syndrome possibly triggered by canakinumab in a patient with adult-onset Still's disease

Macrophage activation syndrome (MAS) is a rare and serious complication of adult-onset Stills disease. We describe a case in a 49-year-old woman with Stills disease refractory to glucocorticoids, methotrexate, and infliximab. Anakinra provided satisfactory disease control for 1 year, after which escape phenomenon occurred. After four tocilizumab injections, cutaneous melanoma developed. The persistent systemic manifestations prompted treatment with two canakinumab injections. Ten days later, she had a spiking fever, dyspnea, low back pain, abdominal pain, odynophagia, and hepatomegaly. Laboratory tests showed liver cytolysis (180 IU/L; N: 10-35), acute renal failure (creatinine, 407 μmol/L; N:50-100), thrombocytopenia (60 G/L; N: 150-400), leukocytosis (12,200/mm(3); N: 4000-10,000), hypertriglyceridemia (5070 mmol/L; N: 0.4-1.6), lactate dehydrogenase elevation (4824 IU/L; N: 135-250), and hyperferritinemia (97 761 μg/L; N:15-150). Examination of a bone marrow biopsy showed phagocytosis. Tests were negative for viruses and other infectious agents. Glucocorticoid therapy (1.5 mg/Kg/d) and intravenous polyvalent immunoglobulins (0.5 g/Kg/d) were given. Her condition improved despite the many factors of adverse prognostic significance (thrombocytopenia, absence of lymphadenopathy, and glucocorticoid therapy at diagnosis). This is the first reported case of MAS after canakinumab therapy in a patient with adult-onset Stills disease.

Acquired hemophilia possibly induced by etanercept in a patient with rheumatoid arthritis.

A 47-year-old woman with rheumatoid arthritis (RA) treated successively with infliximab, abatacept, and etanercept spontaneously developed subcutaneous bruises and a noncompressive hematoma 11 months after starting etanercept therapy (50mg/week). Her prothrombin time was normal but her activated partial thromboplastin time was increased to 2.48 (normal range, 0.85-1.17). She had a circulating anticoagulant (Rosner index, 45; normal,<13) due to an anti-factor VIII antibody in a titer of 45 Bethesda units. Her factor VIII level was less than 1% (normal range, 55-150). The etanercept and leflunomide were stopped and prednisone was given in a daily dosage of 1mg/kg, in combination with rituximab, two 1-g doses at an interval of 2 weeks. After 5 months, persistence of the anti-factor VIII antibody prompted the initiation of azathioprine therapy, 2mg/kg/d. A remission was achieved 9 months after the diagnosis of acquired hemophilia and was sustained at last follow-up after 3 years. This new case of acquired hemophilia in a patient with RA may reflect a simple association or an inducing role of etanercept.

Occurrence of Sweet syndrome under anti-TNF

We report the occurrence of Sweet’s syndrome in a patient treated with adalimumab for Crohn’s disease. The imputability of adalimumab is at issue.

No impact of tumor necrosis-factor antagonists on the joint manifestations of sarcoidosis

Objective The use of anti-tumor necrosis factor (TNF) agents to treat joint manifestations of sarcoidosis has not been described. We evaluated the efficacy and safety of three such biologics in patients with these symptoms refractory to conventional therapy (nonsteroidal anti-inflammatory drugs, corticosteroids, and/or disease-modifying antirheumatic drugs). Methods This retrospective study, covering January 2001 to September 2011, examined clinical–biological parameters collected before anti-TNF treatment (age, sex, duration of disease evolution, drugs taken), and at introduction and under anti-TNF therapy (number of painful and swollen joints, visual analog scale score of global disease activity, disease-activity score of 28 joints with erythrocyte sedimentation rate or C-reactive protein, TNF-antagonist duration). At 3, 6, and 12 months, anti-TNF impact on joints and the therapeutic response according to European League Against Rheumatism criteria used for rheumatoid arthritis were assessed. Results Ten patients’ data were evaluated; some of them had received several anti-TNF agents (median [range] duration on each biotherapy was 10 [4–30] months), which enabled analysis of 19 prescriptions. The total duration of anti-TNF exposure was 17.6 patient-years, which was started a median of 3 (0.33–17) years after sarcoidosis diagnosis. The median numbers of painful and swollen joints were 1 (0–28) and 0 (0–9), respectively. Despite rapid efficacy, after 1 year of treatment, clinical (especially joint) and biological parameters were comparable to pretreatment, and only the corticosteroid dose was significantly lower (P=0.03). One case of mild skin toxicity was noted. Conclusion TNF antagonists allowed significant steroid sparing and were well tolerated, but do not seem to be effective against sarcoidosis joint involvement.

Effectiveness of vedolizumab for Crohn's disease with spondyloarthritis in fail with two TNF blocking agents

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 5 aout 2017

Reply to the comment of Brinster et al. "Acquired hemophilia, rheumatoid arthritis, and TNFα antagonists".

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 8 juillet 2015

Do not forget the joint involvement of sarcoidosis

A letter in response to: Crommelin HA, Vorselaars AD, van Moorsel CH, Korenromp IH, Deneer VH, Grutters JC. Anti-TNF therapeutics for the treatment of sarcoidosis. Immunotherapy 6(10), 1127–1143 (2014).

Soluble vascular endothelial (VE) cadherin and autoantibodies to VE-cadherin in rheumatoid arthritis patients treated with etanercept or adalimumab

OBJECTIVES The aim of this study was to investigate the clinical value of sVE and anti-vascular endothelial-cadherin antibodies (AAVE) in RA treated with etanercept or adalimumab combined with methotrexate. METHODS This was an 18-month prospective multicenter study in which patients had active RA, requiring TNF antagonist. sVE rates and AAVE titers were measured respectively by dot blot and ELISA. The relationship of these biomarkers with parameters reflecting articular or systemic disease activity, progression of structural damage, and response or remission to treatment was analyzed. RESULTS Forty-eight patients received TNF blocking agents. Variation of sVE rates were significantly correlated with that of C-reactive protein (CRP) levels at weeks 6, 12, 26 and 52. A significant decrease in sVE levels was observed in the group of patients exhibiting a decrease in CRP levels as compared to the patient group with unmodified CRP. AAVE at baseline were correlated with rheumatoid factor. Kinetics analysis of sVE levels and AAVE titers showed that their level were not associated with disease activity score and to methotrexate/adalimumab or etanercept response. CONCLUSIONS sVE is a biomarker associated with systemic RA activity under anti-TNF. AAVE are related to autoantibodies usually associated to RA.

The impact of smoking on rheumatoid arthritis outcomes

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 10 janvier 2018