Once-monthly treatment for arthritis

Product: Actemra
 
Company: Genentech 

Pharmacologic class: Interleukin-6 (IL-6) receptor inhibitor 


Active ingredient: Tocilizumab 20 mg/mL; solution for IV infusion after dilution; preservative-free. 


Indication: Moderately to severely active rheumatoid arthritis (RA) in patients who have had an inadequate response to one or more tumor necrosis factor (TNF) blockers. May be used with methotrexate or disease modifying antirheumatic drugs (DMARDs). 

 
Pharmacology: IL-6 is produced by monocytes and lymphocytes in the bloodstream and by synovial and endothelial cells in the joints, leading to systemic and local production of IL-6 in patients affected by inflammatory processes such as RA. Tocilizumab binds specifically to both soluble and membrane-bound IL-6 receptors and has been shown to inhibit IL-6-mediated signaling through these receptors. 


Clinical trials: The efficacy and safety of tocilizumab was assessed in five randomized, double-blind studies in patients >18 years with active RA. Tocilizumab was given every four weeks as monotherapy (Study I), in combination with methotrexate (MTX) (Studies II and III) or other DMARDs (Study IV) in patients with an inadequate response to those drugs, or in combination with MTX in patients with an inadequate response to TNF antagonists (Study V). The primary endpoint was the proportion of patients who achieved an American College of Rheumatology (ACR) 20 response at Week 24. In all studies, patients treated with tocilizumab 8 mg/kg had statistically significant ACR20, ACR50, and ACR70 response rates versus MTX- or placebo-treated patients at Week 24. Patients with inadequate response to DMARDs or TNF antagonist therapy treated with tocilizumab 4 mg/kg had lower response rates compared with patients treated with tocilizumab 8 mg/kg. 


Adults: Give once every four weeks as a 60-minute IV infusion. Initially 4 mg/kg, may increase to 8 mg/kg based on clinical response. Do not start if absolute neutrophil count (ANC) <2,000/mm3, platelets <100,000/mm3, or alanine transaminase/aspartate transaminase (ALT/AST) >1.5 upper limit of normal (ULN). Reduce dose to 4 mg/kg if elevated liver enzymes, neutropenia, or thrombocytopenia occur (see literature). 


Children: Not recommended. 


Precautions: ANC <500 mm3, platelets <50,000 mm3, or ALT/AST >5 ULN: not recommended. Monitor neutrophils, platelets, liver function tests every four to eight weeks. Active hepatic disease or impairment: not recommended. Hepatitis B or C virus or infection. Increased risk of serious or fatal infections (e.g., TB, bacterial sepsis, invasive fungal). Active infections: do not give therapy. Chronic or history of recurring or opportunistic infections. Conditions that predispose to infection. Travel to, or residence in, areas with endemic TB or mycoses. Test for and treat latent TB prior to starting therapy. Monitor closely if new infection develops; discontinue if serious or opportunistic infection or sepsis develops. Monitor lipids four to eight weeks after initiation, then every six months. Immunosuppression. Central nervous system demyelinating disorders. Malignancies. Elderly. Pregnancy (Cat. C). Nursing mothers: not recommended. 


Interactions: Increased risk for infection with concomitant immunosuppressants (e.g., TNF antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies, selective co-stimulation modulators). Avoid live vaccines. Caution with CYP3A4 substrate drugs (e.g., oral contraceptives, lovastatin, atorvastatin). Monitor warfarin, cyclosporine, theophylline, other drugs that are CYP450 substrates with narrow therapeutic indices. 


Adverse reactions: Upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT; infusion reactions, neutropenia, thrombocytopenia, gastrointestinal perforations, increased lipids. 


Containment: Single-use vials (80 mg/4 mL, 200 mg/10 mL, 400 mg/20 mL)—1, 4


Read more >>

Brush teeth to 'prevent' heart disease

People who fail to brush their teeth twice a day are putting themselves at risk of heart disease, research suggests.

The Scottish study of more than 11,000 adults backs previous research linking gum disease with heart problems.

The researchers said more work is needed to confirm if poor oral health directly causes heart disease or is a marker of risk.

A charity added that oral hygiene was just one factor in good heart health.

Data, published in the British Medical Journal was collected on lifestyle behaviours, such as smoking, physical activity and oral health routines.

Participants were also asked how often they visited the dentist and how often they brushed their teeth.

Then nurses collected information on medical history and family history of heart disease, took blood pressure and blood samples.

Overall, six out of 10 people said they visited the dentist every six months and seven out 10 reported brushing their teeth twice a day.

Over the eight-year study there were 555 "cardiovascular events" such as heart attacks, 170 of which were fatal.

Cause and effect

Study leader Professor Richard Watt, from University College London, said future studies will be needed to confirm whether the link between oral health behaviour and cardiovascular disease "is in fact causal or merely a risk marker".

Judy O'Sullivan, senior cardiac nurse at British Heart Foundation, said: "If you don't brush your teeth, your mouth can become infected with bacteria which can cause inflammation.

"However, it is complicated by the fact that poor oral hygiene is often associated with other well known risk factors for heart disease, such as smoking and poor diet."

She added: "Good personal hygiene is a basic element of a healthy lifestyle.

"But if you want to help your heart, you should eat a balanced diet, avoid smoking and take part in regular physical activity."

Professor Damien Walmsley, scientific adviser to the British Dental Association, added it was still unclear whether there was a definite cause and effect between oral hygiene and heart disease.

"Whatever the true position is, we can say with certainty that if people brush teeth twice a day with fluoride toothpaste, visit the dentist regularly and restrict sugary snacks to mealtimes; that this will go a long way towards keeping the teeth and gums in a healthy state for life."

Read more >>