Treatment Of Refractory Sarcoidosis Research Articles

Efficacy and safety of infliximab biosimilar Inflectra® in severe sarcoidosis.

Infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-α) is effective third-line therapy in severe sarcoidosis. The originator product of Infliximab, Remicade®, is expensive, limiting universal access. Recently, a less expensive biosimilar of infliximab, Inflectra®, has become available, but the efficacy and tolerability has not been studied in sarcoidosis. In this retrospective cohort study, 29 patients treated with the infliximab biosimilar Inflectra®, were analysed. Patients received Inflectra® intravenously monthly at a dose of 5 mg/kg. We measured trough levels before every infusion. Before and after 6 months of induction therapy pulmonary function and disease activity were evaluated using Standardised Uptake Value (SUV) of the 18F-fluorodeoxyglucose by positron emission tomography (18F-FDG PET), soluble interleukin-2 receptor (sIL-2R), angiotensin converting enzyme (ACE) and health-related quality of life (HRQOL). In patients with pulmonary sarcoidosis as main treatment indication (n = 15) the predicted FVC improved with 8.1%, p < 0.05. Furthermore, in the whole group HRQoL improved significantly (p < 0.001), whereas SUVmax and sIL-2R significantly reduced (p < 0.001 and p = 0.001 respectively). Hospitalisation due to infections occurred in four patients. None of the patients discontinued Inflectra® due to side-effects. Furthermore, all patients had detectable trough levels indicating development of neutralizing antibodies. Infliximab biosimilar Inflectra® seems effective in the treatment of refractory sarcoidosis with a comparable safety profile to the reference product Remicade®. Inflectra® can be considered as an alternative and less expensive option for patients with refractory sarcoidosis.

⁹⁹mTc-anti-TNF-α antibody for the imaging of disease activity in pulmonary sarcoidosis.

Infliximab, a monoclonal antibody directed against tumour necrosis factor (TNF)-α, is used in the treatment of refractory sarcoidosis. However, the clinical response is variable and a tool to select responders beforehand is highly desirable. In this study we evaluated scintigraphy with technetium-99m ((99m)Tc)-labelled infliximab for the imaging of disease activity in patients with pulmonary sarcoidosis.10 patients were studied using single photon emission computed tomography/computed tomography (CT) 6 h and 20 h after intravenous administration of 370 MBq of(99m)Tc-infliximab. Correlation analysis was performed between tissue accumulation of(99m)Tc-infliximab and laboratory parameters (including soluble interleukin-2 receptor and angiotensin-converting enzyme), lung function parameters (including forced expiratory volume in 1 s and the diffusing capacity of the lung for carbon monoxide) and(18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT.Analysis showed selective and variable accumulation of(99m)Tc-infliximab in the target tissue. Accumulation correlated positively with all four laboratory parameters and negatively with all four lung function parameters, yielding better correlations than serum TNF-α levels or(18)F-FDG PET/CT.(99m)Tc-infliximab accumulation reflects thein situTNF-α expression in an individual patient and therefore provides valuable information on the presence of the biological target for anti-TNF-α therapy.

Adalimumab successful in sarcoidosis patients with refractory chronic non-infectious uveitis

IntroductionAdalimumab, a humanized monoclonal antibody targeted against TNF-α, has proved to be successful in the treatment of uveitis. Another anti-TNF-α agent, i.e., infliximab, has been reported of benefit in the treatment of refractory sarcoidosis. The aim of this prospective case series was to evaluate the effect of adalimumab on intraocular inflammatory signs and other relevant clinical manifestations (lung function, serological inflammatory parameters, and fatigue) of sarcoidosis.MethodsSarcoidosis patients with refractory posterior uveitis (n = 26, 17 females, 41 eyes in total) were systematically followed for 12 months after initiation of adalimumab 40 mg sc once a week. Inclusion criteria were non-responsiveness to prednisone and methotrexate (MTX) or intolerance to these drugs. Adjunctive therapy with prednisone and MTX was tapered during treatment with adalimumab. Localization and improvement, stabilization or deterioration of intraocular inflammatory signs was scored. Pulmonary function- and laboratory testing were performed and Fatigue Assessment Scale was completed. Results at baseline, 6 months, and 12 months were compared.ResultsChoroidal involvement resolved in 10/15 patients, five had partial improvement; vasculitis resolved in 1/1 patient; papillitis resolved in 7/8 patients, one had partial response; macular edema resolved in 5/8 patients, three had partial response; vitreous cleared completely in 5/5 patients. Overall outcome regarding intraocular inflammatory signs showed improvement in 22 patients (85%) and stabilization in four patients (15%). At 12 months, no recurrences were reported in those successfully treated. Laboratory parameters of inflammatory activity (C-reactive protein; serum angiotensin-converting enzyme and soluble interleukin-2 Receptor) improved (p < 0.01). Moreover, fatigue improved in 14/21 (67%) of the patients suffering from fatigue and the diffusion capacity for carbon monoxide (DLCO) improved in 7/8 (88%) of patients with a decreased DLCO (p < 0.01). The dosage of both prednisone and MTX could be tapered down significantly (p < 0.01 and p < 0.05, respectively).ConclusionsAdalimumab appeared successful in sarcoidosis patients with refractory chronic non-infectious uveitis showing improvement in intraocular inflammatory signs as well as in other relevant clinical indicators of disease activity. Future randomized studies are needed to determine the optimal dosage, dose interval and duration of therapy in refractory multisystemic sarcoidosis.

Quantiferon test for tuberculosis screening in sarcoidosis patients

Tumour necrosis factor-alpha (TNF-α) inhibitors have been introduced in the treatment of refractory sarcoidosis. These biologics may reactivate latent tuberculosis infection (LTBI). Despite its known limitations, the tuberculin skin test (TST) is currently used for the diagnosis of LTBI in Danish sarcoidosis patients. We report the results of a screening using the interferon-gamma release assay (IGRA) QuantiFERON TB Gold (QFN) for the diagnosis of LTBI. We aimed to assess whether the QFN is reliable for diagnosing LTBI among sarcoidosis patients and if results are influenced by disease activity or immunosuppressive treatment. A prospective study was performed from 2005 to 2007 among sarcoidosis patients who were candidates for TNF-α inhibitor treatment. Information on immunosuppressive treatment was obtained from the medical records. Disease activity was assessed by biochemistry, chest roentgenograms and pulmonary function tests. The predictive value of QFN results was evaluated by follow-up in the Danish National Tuberculosis Registry. A total of 44 sarcoidosis patients (22 men) with a median age of 39 y (range 25-59 y) were enrolled; 93% had a negative QFN test result and 7% had an indeterminate result. Forty-three percent had disease activity and 57% (n = 25) received immunosuppressive treatment. There was no significant difference in QFN interferon-γ response between subjects with or without disease activity (p > 0.4) and between treated vs non-treated patients (p > 0.5). At follow-up using the Danish tuberculosis registry, there was no occurrence of tuberculosis among study participants. The predictive value of the QFN seems good among Danish sarcoidosis patients and the results appear to be unaffected by sarcoidosis disease activity and immunosuppressive treatment.

Adalimumab-induced noncaseating granuloma in the bone marrow of a patient being treated for rheumatoid arthritis

Sarcoidosis is a multisystemic disease characterized by noncaseating granulomatous infiltration, primarily of the lungs and lymphatic system. While reports of the efficacy of adalimumab in the treatment of refractory sarcoidosis have been mixed, the more widely used infliximab has demonstrated clear efficacy in this disease. The association between tumor necrosis factor (TNF)-inhibitors and noncaseating granulomas in the lung has been reported in literature. With the exception of one patient treated with adalimumab, who developed pulmonary granuloma, the remaining patients described in literature were treated with etanercept. The current case study is, to our knowledge, the first to describe adalimumab-induced noncaseating granulomas in the bone marrow of a patient being treated for rheumatoid arthritis and suggests that although TNF-inhibitors are used in the treatment of granulomatous disorders, their use should be carefully monitored as, in rare cases, TNF-inhibitors may leave sufficient cytokine activation to support granuloma formation.

Refractory Vertebral Sarcoidosis Responding to Infliximab

Treatment of refractory sarcoidosis may be challenging for clinicians. Despite treatment with conventional therapy, sarcoidosis may be progressive and debilitating. Previous studies have implicated a role for tumor necrosis factor-alpha in granuloma formation as seen in sarcoidosis. Tumor necrosis factor-alpha inhibitors are currently approved to treat rheumatoid arthritis, Crohn disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, and juvenile rheumatoid arthritis. There have been recent case-reports supporting treatment of refractory and multisystem sarcoidosis with such agents. We report a case of sarcoidosis, involving the lung and vertebrae, which was refractory to conventional therapy. Our patient's clinical symptoms and radiologic lesions of vertebral sarcoid dramatically improved after treatment with infliximab.

TNF-alpha inhibitors in treatment of refractory sarcoidosis with severe CNS involvement

RATIONALE: Although etiology of sarcoidosis remains unclear the literature suggests that TNF-alpha is an important factor in pathophysiology of granulomatous inflammation and disease activity. We report a case of steroid and methotrexate resistant systemic sarcoidosis with CNS involvement with clinical and radiological response to anti-TNF-alpha therapy.

Efficacy of Minocycline in the Treatment of Refractory Sarcoidosis

Efficacy of Minocycline in the Treatment of Refractory Sarcoidosis