Early effects of tumor necrosis factor inhibition on bone homeostasis after soluble tumor necrosis factor receptor use

BACKGROUND/AIMS: Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients. METHODS: Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched). RESULTS: Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 +/- 2.12 pg/mL at baseline to 2.51 +/- 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755). CONCLUSIONS: RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.

Psoríase pustulosa palmoplantar tratada com etanercepte: relato de caso / Palmoplantar pustular psoriasis treated with etanercept

Contexto: A psoríase pustulosa palmoplantar (PPPP) é uma das apresentações clínicas da psoríase, muitas vezes de difícil tratamento, podendo-se utilizar diversos medicamentos tópicos e sistêmicos. O uso dos anti-TNFα no tratamento das formas pustulosas de psoríase é controverso, visto que a resposta clínica é variável, além desta classe de medicação biológica poder desencadear psoríase pustulosa. Descrição do Caso: Doente feminina, 60 anos, branca, com diagnóstico de PPPP há 12 anos e artrite psoriásica há seis anos. Antecedentes pessoais relevantes: hipertensão arterial sistêmica, hipertrigliceridemia e obesidade. Apresentou refratariedade tanto aos tratamentos tópicos instituídos (corticóides e emolientes) quanto aos sistêmicos (metotrexate, dapsona, colchinina e acitretina), tendo evoluído com excelente resposta terapêutica com etanercepte (administrado semanalmente, por via subcutânea, na dose de 50 mg). Discussão: Os anti-TNFα são eficazes no tratamento da psoríase em placas moderada a grave.Mas, o tratamento da PPPP com anti-TNFα não é classicamente preconizado. Segundo a literatura a resposta terapêutica com este tipo de medicamento é variável na PPPP. Além disso, os anti-TNFα podem desencadear quadro de pustulose palmoplantar. No entanto, há relatos de sucesso terapêutico com anti-TNFα em casos refratários de PPPP. Em função das comorbidades da paciente e após terem sido esgotadas as possibilidades terapêuticas clássicas, optamos pelo uso do etanercepte, que se mostrou eficaz.A doente iniciou tratamento em abril de 2008 e mantém o uso do etanercepte até a presente data, estando em remissão da doença. Conclusão: Destacamos a possibilidade do uso de anti-TNFα em paciente com PPPP refratária ao tratamento convencional. No nosso caso, o etanercepte mostrou-se eficaz e seguro, não tendo a doente apresentado nenhum efeito adverso grave.

Background: Palmoplantar pustular psoriasis (PPPP) is one of the clinical presentations of psoriasis, often difficult to treat, can be used several topical and systemic. The use of anti-tumor necrosis factor alpha (anti-TNFα) in the treatment of pustular forms of psoriasis is controversial, with a variable clinical response, outside this class of biological medication may trigger pustular psoriasis. CASE REPORT: Patient 60, female, white, with a diagnosis of PPPP for 12 years and psoriatic arthritis for 6 years. Relevant personal history: hypertension, hypertriglyceridemia andobesity. Presented refractory to topical treatments (corticosteroids and emollients) and systemic (methotrexate, dapsone, colchicineand acitretin), having evolved with excellent response to treatment with etanercept (administered weekly by subcutaneous injection at a dose of 50 mg). Discussion: The anti-TNFα are effective in the treatment of psoriasis in moderate to severe plaque. But, inthe treatment of PPPP is not classically recommended. According to the literature, the therapeutic response with this type of drug is variable in PPPP. In addition, anti-TNFα may trigger clinical of palmoplantar pustulosis. However, there are reports of therapeutic success with anti-TNFα in refractory cases of PPPP. Due to patient’s comorbidities, and after having exhausted the possibilities classical therapies, we chose the use of etanercept, which proved effective. The patient began treatment in April 2008 and keeps the use of etanercept until the present date, being in remission.Conclusion: We emphasize the possibility of using anti-TNFα in patients with PPPP refractory to conventional treatment. In our case, etanercept was effective and safe, not having the patient presented any serious adverse events.

Anti-TNF-alpha Therapy for Ankylosing Spondylitis

BACKGROUND: This review evaluated the safety and efficacy of etanercept in patients with ankylosing spondylitis (AS). METHODS: Of 59 patients with AS, this study reviewed 11 patients who were refractory to conventional therapy and treated with etanercept from September 2005 to January 2008. The mean follow-up duration was 13.6 months. The general improvement was evaluated by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and adverse effects, complications and inflammatory markers were also assessed. RESULTS: The mean BASDAI decreased from 7.1 +/- 1.6 before treatment to 4.2 +/- 1.8 at 3 months after the etanercept treatment (p = 0.001). The mean erythrocyte sedimentation rate and C-reactive protein were decreased significantly by the etanercept treatment. The greatest improvement in symptoms was enthesitis, followed by skin involvement and morning stiffness. There was a significant difference in the improvement in BASDAI along with the follow up duration (p = 0.04). A serious infection was observed as a complication in 1 case. CONCLUSIONS: These results suggest that etanercept can induce significant improvement in most patients with less damage. A trial of tumor necrosis factor inhibition is indicated in all AS patients who do not achieve adequate disease control with disease-modifying antirheumatic drugs, such as methotrexate, leflunomide etc. The patients treated with etanercept should be educated about the possibility of infection and monitored closely.

Uso de biológicos para el tratamiento de la psoriasis / Biologic therapies for psoriasis

La psoriasis es una enfermedad inflamatoria crónica, mediada por los linfocitos T, que afecta a 1 por ciento-3 por ciento de la población mundial. Afectando primordialmente la piel y las articulaciones (artritis psoriática), también está asociada con otras condiciones inflamatorias, como son la enfermedad intestinal inflamatoria y patología coronaria, entre otras. El tratamiento de la psoriasis viene dado según su extensión y severidad, variando desde modalidades locales (tópicas e intralesionales), fototerapia, hasta regímenes sistémicos. Estos últimos generalmente conllevan efectos secundarios cuando son utilizados a largo plazo. Hoy en día, gracias a los últimos avances científicos, se ha logrado profundizar el entendimiento de la patogénesis de la psoriasis, dando lugar a terapias específicamente dirigidas conocidas como “biológicos”. A continuación se discutirán los principales biológicos utilizados en el tratamiento de la psoriasis en placa moderada a severa: efalizumab, alefacept, etanercept, infliximab, adalimumab e inhibidores de la interleuquina (IL) 12/23.

Psoriasis is a chronic T cell-mediated inflammatory disease that mainly affects the skin and joints, and is present in 1 percent-3 percent of world population. It is also associated to other inflammatory conditions such as inflammatory intestinal disease and coronary pathologies, among others. Conventional treatments for moderate to severe psoriasis are associated to broad band immunosuppression and/or organ-toxicities which can be problematic when used in a long-term. Advances in the understanding of psoriasis pathogenesis have led to targeted therapy in the form of biologics. These agents have gained popularity as safe, effective and convenient alternatives for the treatment of chronic moderate to severe plaque psoriasis. This review focuses on the main biologics used in the treatment of moderate to severe plaque psoriasis: efalizumab, alefacept, etanercept, infliximab, adalimumab and interleukin inhibitors (IL) 12/23. Mechanisms of action, guidelines for usage, efficacy data, and safety concerns will be discussed for each biologic. In addition, the new Th17 biologics and their role in psoriasis pathogenesis will also be examined.