CAMBRIDGE, England, June 18, 2010 /PRNewswire/ -- Mundipharma announced today that 13 European countries to date have received approval of Lodotra(R) (modified-release prednisone), a new treatment for rheumatoid arthritis (RA) which offers the benefits of conventional prednisone, with the added advantage of a clinical reduction in morning stiffness, a barrier to the morning functioning of people with RA.
A complexity of symptoms including physical dysfunction, stiffness and pain in joints (particularly affecting the hands) first thing in the morning can be a barrier to normal morning function. Pain and stiffness in the morning have been linked with increased concentrations of inflammatory chemicals, known as cytokines that circulate in the blood(1). Interleukin-6 (IL-6) is one such cytokine which peaks in the early morning hours, manifesting itself as inflammation, pain and stiffness in joints upon waking, affecting ability to work and impacting on quality of life(1,2,3.)
Taken at 10.00pm, Lodotra utilises a unique modified-release mechanism to begin releasing low-dose prednisone about four hours after ingestion, at a time in the early morning when inflammation builds up and damage occurs1. Maximum levels of prednisone in the blood are reached six hours after ingestion, at the optimum time when levels of pro-inflammatory cytokines such as IL-6 are at their natural peak, reducing the impact of joint stiffness for people with RA in the first few hours after waking(1,4,5,6). Conventional prednisone taken in the morning does not adequately control symptoms of pain and stiffness(1).
The need for a new treatment option for those who suffer from morning stiffness is supported by results from new research involving people with RA and physicians, carried out by Ipsos MORI and commissioned by Mundipharma across 11 European countries. Almost three quarters (74%) of people across Europe living with pain and stiffness in the morning as a result of their RA say that they are either unemployed, early retired or on sick leave as a result of RA and over half (58%) say they are frustrated emotionally because they find it more difficult to do everyday tasks(7). Nearly two thirds (60%) of people with RA say that pain and stiffness in the morning controls their lives(7).
Maurizio Cutolo, Professor of Rheumatology, Director Research Laboratory and Academic Unit of Rheumatology, University of Genova says: The stiffness and pain experienced in the morning by people with RA appear to have a direct impact on quality of life, particularly in relation to work. 74% of people with RA questioned said that these symptoms have a significant impact on their work, with over a quarter confessing that the pain and stiffness they experience in the morning has been a direct factor in slowing their career progression - one in seven had to change profession(7). There is therefore a clear need for new treatment options to specifically address the issue of morning stiffness.
Over a quarter (29%) of those with RA questioned state that it can take between one and a half and three hours before they are even able to start their day due to pain and stiffness in the morning resulting from their RA7. This is in direct contrast to the opinion of the majority of rheumatologists, 62% of whom believe pain and stiffness in the morning only lasts between 30 minutes to one hour8.
Describing her experience with rheumatoid arthritis, Danielle Leys from Belgium says: As my rheumatoid arthritis has progressed I find it very difficult to carry out tasks in the morning. The hardest thing to accept is not being able to take my grandchildren to school any more - I'm not even able to carry them in my arms and I find that very upsetting. I used to work as a typist but because of the stiffness in my hands, I had to leave my job. My biggest wish is that I could do everything myself without the help of others - it would just be nice to get my old life back.
Approval of Lodotra is supported by clinical data which showed that after 12 weeks of treatment, evening administration of Lodotra resulted in a significant decrease in duration of morning stiffness of the joints than was recorded after morning administration of conventional prednisone(1).
A total of 288 patients with active rheumatoid arthritis took part in the Circadian Administration of Prednisone in Rheumatoid Arthritis (CAPRA-1) trial. Participants were randomly assigned to 12 weeks of double-blind treatment, with either modified-release prednisone (Lodotra) or immediate release (standard) prednisone1. At the end of the treatment, those who were administered Lodotra achieved a significantly higher mean relative change in duration of morning stiffness of the joints from baseline than with immediate-release prednisone (-22.7% vs -0.4%; [95% CI 0.49-44.30]; p=0.045)(1). Results also showed Lodotra significantly reduced levels of IL-6 serum concentrations after three months, but conventional prednisone had no effect on IL-6 levels1. In addition to reducing morning stiffness, this study showed that therapy with Lodotra was well tolerated and had a safety profile similar to the same dose of conventional prednisone(1).
In another Phase III trial (CAPRA-2) treatment with Lodotra in combination with a disease-modifying anti-rheumatic drug (DMARD) resulted in a clinically significant improvement in ACR 20 response rate, the primary endpoint of the trial, compared to DMARD alone. Improvements in both pain and morning stiffness - barriers to morning function - were demonstrated(9). In this trial, Lodotra was also found to be well tolerated(10).
Notes to Editors:
About Lodotra
Lodotra is licensed for the treatment of rheumatoid arthritis and associated morning stiffness. It is administered in the form of a specially formulated tablet which utilises modified-release technology. The active drug is contained within an outer tablet layer which acts as a barrier between the gastrointestinal fluids in the stomach and the active core. Water in the digestive tract causes the outer layer to break and release prednisone from the core. The innovative technology allows the drug to be delivered at a pre-determined release rate, which in this case is four hours after ingestion.
Lodotra was first launched in Germany in April 2009, and has been approved for the treatment of RA and associated morning stiffness in a further 12 countries including Austria, Belgium, Denmark, Finland, France, Luxembourg, the Netherlands, Norway, Poland, Portugal, Sweden and the United Kingdom. Studies are planned to investigate the use of modified-release prednisone in other conditions in which IL-6 plays a role such as severe asthma and polymyalgia rheumatica.
For more information: http://www.lodotra.com
(R) Lodotra is a registered trade mark.
About Mundipharma
The Mundipharma/Napp/Norpharma independent associated companies, including Mundipharma, Purdue and Napp, are privately owned companies and joint ventures covering the world's pharmaceutical markets. The companies worldwide are dedicated to bringing to patients with severe and debilitating diseases the benefits of novel treatment options in fields such as rheumatoid arthritis, severe pain, haemato-oncology and respiratory disease.
For more information: http://www.mundipharma.co.uk
About Horizon Pharma
Horizon Pharma, Inc., the licensor of Lodotra, is a late-stage biopharmaceutical company focused on the development and commercialization of innovative medicines for pain-related diseases and chronic inflammation.
For more information: http://www.horizonpharma.com.
About the research
This research was carried out across 550 rheumatologists and 750 patients aged between 18 and 75 from 11 countries across Europe: the United Kingdom, Spain, France, Italy, Sweden, Denmark, The Netherlands, Norway, Belgium, Finland and Poland. All patients surveyed had been diagnosed with RA for at least 6 months and all suffer from impaired morning function at least 3 times a week.
References
1. Buttgereit F, Doering G, Schaeffler A et al. Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial. Lancet 2008; 371: 205-214
2. Westhoff G, Buttgereit F, Gromnica-Ihle E et al. Morning stiffness and its influence on early retirement in patients with recent onset rheumatoid arthritis. Rheumatology 2008; 47(7): 980-984
3. Kirwan JR, Clarke L, Hunt LP et al. Effect of novel therapeutic glucocorticoids on circadian rhythms of hormones and cytokines in rheumatoid arthritis. Ann NY Acad Sci 2010; 1193: 127-133
4. Cutolo M, Straub RH and Buttgereit F. Circadian rhythms of nocturnal hormones in rheumatoid arthritis: translation from bench to bedside. Ann Rheum Dis 2008; 67: 905-908
5. Cutolo M et al. Circadian rhythms in RA. Ann Rheum Dis 2003; 62: 593-596
6. Cutolo M et al. Circadian melatonin and cortisol levels in rheumatoid arthritis patients in winter time: a north and south Europe comparison. Ann Rheum Dis 2005; 64(2): 212-216
7. Ipsos MORI RA patient study May 2010. Participants: 750 adults
This research was commissioned by Mundipharma International
8. Ipsos MORI Rheumatologist study May 2010. Participants: 550 rheumatologists
This research was commissioned by Mundipharma International
9. Buttgereit F et al. CAPRA-2 efficacy data presented at EULAR 2010
10. Buttgereit F et al. CAPRA-2 safety data presented at EULAR 2010
SOURCE: Mundipharma
CONTACT: For further information please contact: Mani Reel,mani.reel@redconsultancy.com , +44-207-025-6584; Ellie Moffat,eleanor.moffat@redconsultancy.com , +44-207-025-6584.
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