Enbrel (etanercept) is an approved treatment, marketed by Amgen, to treat ankylosing spondylitis and prevent joint damage caused by this disease.
It was first approved by the U.S. Food and Drug Administration in 1998 to treat moderate to severe rheumatoid arthritis (RA), and its use was extended to other rheumatic conditions, such as psoriatic arthritis (2002), as well as skin diseases like plaque psoriasis (2004). Enbrel approved to treat ankylosing spondylitis in 2003.
A biosimilar, called Erelzi (etanercept-szzs), was approved by the FDA in 2016.
How Enbrel works
Enbrel is an inhibitor of tumor necrosis factor (TNF), a cell-signaling molecule that plays an important role in the immune system to help the body fight diseases and infections.
In people with ankylosing spondylitis, however, the immune system produces too much TNF, which causes inflammation, as well as pain and swelling in the joints of the spine.
When Enbrel binds to TNF, it blocks its activity so as to reduce inflammation and pain.
Because Enbrel affects the immune system, its use can raise the risk of infections, including serious infections like tuberculosis.
Enbrel in clinical trials
The effectiveness of Enbrel in ankylosing spondylitis has been evaluated in several clinical trials.
Results of the first trial were published in 2002 in The New England Journal of Medicine. The trial included 40 patients with active, inflammatory ankylosing spondylitis who were assigned randomly to received Enbrel (under-the-skin injections, 25 mg) or placebo for four months. A clear majority — 80 percent — treated with Enbrel showed significant improvement, with response to treatment assessed using the Assessment in Ankylosing Spondylitis 20 (ASAS20) scale that includes measures of spinal pain, stiffness and joint function and aims for evidence of a 20 percent improvement over baseline or study start, compared to 30 percent of those on placebo who also showed an ASAS20 response. Enbrel was also associated with a greater improvement in several other measures, such as chest expansion, erythrocyte sedimentation rate, and C-reactive protein level.
Thirty-six patients then enrolled in an open-label trial extension to either start (placebo group) or continue on Enbrel treatment for six months. Placebo-group patients showed a rapid response and benefits similar to those seen in the original treatment group, while initially treated patients showed sustained and continued improvement throughout the trial’s 10-month period. At its end, 29 of the 36 total patients (81%) achieved ASAS50, representing a 50% improvement over baseline scores, and 15 of the 36 (42%) achieved the ASAS70, a 70% improvement.
A clinical trial in Europe that concluded in 2004 assigned 45 of 87 patients to treatment with 25 mg of Enbrel for 12 weeks. Results showed that 60% had ASAS20 responses, compared to only 23% of patients who received placebo. ASAS50 and ASAS 70 responses were seen in 49 percent and 24 percent of patients receiving Enbrel, respectively. These results were then confirmed in a 96-week extension study (NCT00421980) in 81 patients, where 83 percent had ASAS20 responses.
In a follow-up study that monitored the effectiveness and safety of Enbrel in 257 people with ankylosing spondylitis, responses to treatment lasted almost two years, with 74 percent achieving an ASAS20 response after 96 weeks of treatment. Similar long-term efficacy results were demonstrated in another 54-week observational study.
Two 12-week trials compared the effectiveness of 50 mg of Enbrel given once weekly with that of 25 mg of Enbrel twice weekly. Both doses showed similar results in the measures of disease activity analyzed (ASAS20 response at week 12 was the primary goal), and acceptable safety. Treatment with both doses was also reported to significantly improve patients’ quality of life and functional status. These results suggested that both doses of Enbrel were equally effective in treating ankylosing spondylitis.
The Phase 4 ASCEND study (NCT00247962), completed in 2008, compared the effectiveness of Enbrel (50 mg once weekly) and Azulfidine (sulfasalazine), used to treat RA and other autoimmune diseases, in 566 people with ankylosing spondylitis. Patients were treated for 16 weeks, and results showed that Enbrel was significantly more effective than Azulfidine in improving the signs and symptoms of the disease in axial skeleton and peripheral joints (assessed using the ASAS20 scale).
The effectiveness in patients who failed to respond to previous therapies was evaluated in two observational studies. Both showed that switching from Remicade (inﬂiximab) to Enbrel led to good clinical responses.
A number of clinical trials are still ongoing and recruiting participants to further test this therapy in ankylosing spondylitis.
One Phase 3 study (NCT02809781), taking place at a single site in China and running through December 2018, is evaluating the safety and effectiveness of Enbrel in comparison to a mesenchymal stem cell therapy. It is currently recruiting ankylosing spondylitis patients.
A Phase 2 registry study (NCT02456363) that started in May 2015 and is recruiting patients in Taiwan, is investigating TNF therapies including Enbrel, Humira (adalimumab) and Simponi (golimumab) in patients with ankylosing spondylitis for 92 weeks.
A Phase 4 study (NCT02509026) is evaluating the benefits and risks of Enbrel withdrawal in ankylosing spondylitis patients who achieved a significant clinical response to treatment. This study is currently enrolling about 200 eligible patients at 82 sites across the U.S. and Europe, and in a few other countries, and runs through November 2019. More information is available by clicking on its identification number.
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