Clazakizumab for Adults with Active PsA

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The Rheumatologist

Although the pathogenesis of psoriatic arthritis (PsA) is not fully understood, the pleiotropic inflammatory cytokine interleukin-6 (IL-6), which has a known role in synovitis, local and systemic inflammation, and the promotion of bone resorption in rheumatoid arthritis (RA), may play a role. Serum levels of IL-6 are increased in patients with psoriasis, and the up-regulation of proinflammatory cytokines, including IL-6, in PsA synovial tissue has been reported. In patients with PsA, IL-6 levels correlate with the number of affected joints, elevation of the erythrocyte sedimentation rate, and C-reactive protein (CRP) level. Additionally, a few case reports of successful use of anti–IL-6 receptor biologic therapy to treat PsA exist, although results have been conflicting. Taken together, these findings make IL-6 a potential therapeutic target in PsA.

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Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: Results of a phase III study.

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Arthritis Rheumatol. 2015 Mar 2. doi: 10.1002/art.39093. [Epub ahead of print]

Genovese et al

Abstract

Objectives. To evaluate the efficacy and safety of sarilumab in combination with methotrexate (MTX) for treatment of rheumatoid arthritis (RA).

Methods. Adults with moderate-to-severe RA and inadequate response to MTX were randomized (1:1:1) to sarilumab 150mg, 200 mg, or placebo every 2 weeks (q2w) with MTX for 52 weeks.

Results. Baseline characteristics were similar among groups. For all three co-primary endpoints, sarilumab 150mg and 200mg groups demonstrated statistically significant improvements vs placebo: ACR20 response at Week 24 (58.0%, 66.4% vs 33.4%; p<0.0001), HAQ-DI at Week 16 (−0.53, −0.55, vs −0.29; p<0.0001) and mTSS at Week 52 (0.90, 0.25 vs 2.78; p<0.0001).

The most common treatment-emergent adverse event was infection; serious infections incidence was 2.6%, 4.0%, and 2.3% (sarilumab 150mg, 200 mg, and placebo, respectively). Elevations in alanine aminotransferase >3-fold the upper limit of normal in 9.5%, 8.0%, and 2.1% of patients led to discontinuation of 24 patients. Elevated total cholesterol levels were observed in 36.8%, 43.0% and 18.3% of sarilumab 150mg, 200 mg and placebo patients, respectively. Neutrophil counts 500–

Conclusions: In RA patients treated with sarilumab (150mg and 200mg q2w) in combination with MTX, both doses provided sustained clinical efficacy, significantly improving symptomatic, functional, and radiographic outcomes. Sarilumab was generally well tolerated. The adverse events observed in this study were consistent with IL-6 signaling blockade.

What’s a Biologic?

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A Biological is a protein that blocks another protein (cytokine) that plays an important role in the inflammation of some rheumatic diseases. The most well known are TNF and Interleukin 6 (IL-6). Not always, biologics block cytokines. They may also target cells that have an important role in inflammation or block the interaction of different cells, which, stimulates inflammation. The fundamental difference with other therapeutic agents is that most of the drugs are chemical compounds. However, biologics just for being proteins have a very complex structure and higher molecular weight, and they are degraded in the stomach quickly, which, prevent to administer orally. Therefore, biologics are only given intravenously or subcutaneously (such as insulin).

Note: Biological are not exclusive treatments for rheumatic diseases, other diseases, such as cancer and many others, also have biological treatment

See section Biologics, to find the topic in extend