NICE 2001/ 025
Issued: 26 July 2001

Press Release

NICE issues guidance on Cox II inhibitors for osteoarthritis and rheumatoid arthritis

The National Institute for Clinical Excellence has today issued guidance on the use of four drugs for the treatment of osteoarthritis and rheumatoid arthritis to the NHS in England and Wales. The four drugs, celecoxib, etodolac, rofecoxib and meloxicam, are Cox II selective inhibitors and are a type of non-steroidal anti-inflammatory drug (NSAID) used for short-term treatment of acute inflammation in joints caused by arthritis.

The full guidance and detailed recommendations are available on the NICE website. In summary the Institute recommends that:

  • Cox II selective inhibitors are not recommended for routine (regular) use in patients with rheumatoid arthritis or osteoarthritis.
  • They should only be used instead of standard NSAIDs, in people with rheumatoid arthritis or osteoarthritis who may be at 'high risk' of developing serious gastrointestinal problems. High risk patients include those age 65 or over, those already taking other medicines which can cause gastrointestinal problems (such as ulcers) and those who have existing gastrointestinal problems.
  • All NSAIDs can cause side effects and they should only be prescribed when there is a demonstrable clinical need and they should only be used for the type of disease that they are licensed for. Long-term use of these products should be avoided unless the person taking the medicine is monitored and their condition is checked to see if these medicines are still required.

Andrew Dillon, Chief Executive of the Institute, said: "The Institute's guidance provides advice to both the NHS and people with arthritis on the role of Cox II selective inhibitors in the treatment of this debilitating condition. We recommend they be considered in preference to standard treatments only when there is a high risk of patients suffering from gastrointestinal problems as a side effect of treatment".

Ends

Notes for Editors

Background

1. Arthritis is a general term used to describe a disease of the joints. Symptoms can include some or all of the following: pain, swelling, stiffness, difficulty in movement and redness of the skin over the affected joint. The two most common forms of arthritis are rheumatoid arthritis and osteoarthritis. There are 1,325,000 -1,750,000 people with osteoarthritis and 250,000-500,000 people with rheumatoid arthritis in England and Wales.
   
2. Rheumatoid arthritis is a condition in which the joints are inflamed and damaged over a long period of time. Treatment aims to improve quality of life by controlling the symptoms of the disease which can include inflammation (swelling of the joint) and pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are often used, and they can be combined with other medicines that can alter the way the disease progresses.
   
3. Osteoarthritis is a form of arthritis that gradually damages the cartilage that lines the joints. Although some medicines are used with the aim of slowing down the disease, the main aim of treatment is to control pain with simple pain relieving drugs.
   
4.

People at 'high risk' of developing serious gastrointestinal problems include:

  • those aged 65 years and over;
  • those using other medicines that are known to increase the likelihood of gastrointestinal problems
  • those with some other diseases related to their osteoarthritis or rheumatoid arthritis (these are called serious co-morbidities); and
  • those requiring the long term use of standard NSAIDs at the maximum dose.
5. The risk of problems caused by NSAIDs is particularly increased in patients with a previous history of gastroduodenal ulcer, gastrointestinal bleeding or gastroduodenal perforation. The use of even a Cox II selective drug should therefore be considered especially carefully in this situation.
   
6. People who have cardiovascular disease as well osteoarthritis or rheumatoid arthritis, should not receive a Cox II selective inhibitor on a regular basis. Also many people with cardiovascular disease take low dose aspirin and this can increase the risk of gastro-intestinal problems. Therefore in people who are taking low dose aspirin, the benefit of using a Cox II selective drug (to decrease the likelihood of problems in the stomach or intestines) is reduced. Prescribing Cox II selective agents instead of standard NSAIDs in this situation is therefore not justified.
   
7. In the past some medicines that can protect the stomach or intestine have been prescribed at the same time as the Cox II selective inhibitors with the aim of further reducing potential gastrointestinal problems. There is no evidence to support the prescription of these medicines with the Cox II selective inhibitors. NICE has previously issued guidance on some of these medicines, which are called proton pump inhibitors (PPIs).
   
8. The Institute's process for developing appraisal guidance allows for an appeal should it be required. Appeals were made in respect of this appraisal, and they were heard on the 7th June 2001. None of the appeals were upheld. The full decision of the appeal panel (5 pages) is available from the Institute's web site, a summary follows
   
9.

The three grounds upon which the Appeal Panel can hear an appeal are:

  • Ground One: the Institute has failed to act fairly and in accordance with the Appraisal Procedure set out in the Institute's Interim Guidance for Manufacturers and Sponsors;
  • Ground Two: the Institute has prepared guidance which is perverse in the light of the evidence submitted;
  • Ground Three: the Institute has exceeded its powers.
10. Pharmacia and Pfizer appealed on the first and second grounds. Merck Sharp & Dohme appealed on the second and third grounds. MSD withdrew their appeal on the first ground at the appeal hearing.
   
11. The appeals were heard on 7th June by an Appeal Panel comprising:Dr Susanna Lawrence (Chair of the Appeal Panel and non-executive Board Member), Mr Frederick George (non-executive Board Member), Ms Mercy Jeyasingham (non-executive Board Member), Dr Angus Sim (industry representative) and Ms Gill Donovan (patient representative)
   
12.

Appeals were made

  • suggesting that Committee had not considered certain evidence
  • regarding the guidance recommendations for patients with cardivascular disease and those taking aspirin
  • suggesting that there were errors in the guidance document
  • as the committee hadn't differentiated between Cox II inhibitors and also between other NSAIDs
  • suggesting that the Institute had breached the Transparency Directive

All of the appeals were rejected.

   
The Technologies
   
13. Cox II inhibitors are a type of non-steroidal anti-inflammatory drug (NSAID) used for the short-term treatment of acute inflammation in the joints caused by arthritis.
   
14. This group of drugs includes celecoxib (Celebrex) and etodolac (Lodine SR) which can be used for rheumatoid arthritis and osteoarthritis; rofecoxib (Vioxx) which is only used for osteoarthritis and meloxicam (Mobic) which is used for acute osteoarthritis and the long-term treatment of rheumatoid arthritis.
   
15. Cox II selective inhibitors and other non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and stiffness in inflammatory rheumatoid arthritis and for the short-term management of pain in osteoarthritis.
   
Implications for the NHS
   
16.

Switching high-risk OA and RA patients to Cox II selective inhibitors would lead to an annual incremental cost of approximately £25 million to the NHS. This figure is based on the following assumptions:

  • half of the 'high risk' patients will be offered Cox II selective inhibitors;
  • each product has an equal market share of 25%;
  • the proportion of patients aged over 65 is 58% for OA and 45% for RA;
  • the percentage of patients with previous gastrointestinal events is 8%;
  • the average treatment duration is 180 days a year; and
  • the relative risk reduction is constant across different risk groups.
General Information
   
17. Copies of the full guidance and supporting documentation will be available on the NICE web site (www.nice.org.uk) from midday on Thursday 26th July 2001.
   
18. Health professionals are expected to take the Institute's guidance fully into account when exercising their clinical judgement for individual patients. This guidance does not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.
   
19. The National Institute for Clinical Excellence (NICE) is a part of the NHS. Part of its work is technology appraisals. The Institute produces guidance for both the NHS and patients on medicines, medical equipment and clinical procedures based on evidence of clinical and cost effectiveness. Each appraisal takes an average 12 months to complete and involves the manufacturers of the technology, groups that represent patients/carers and healthcare professionals.
   
20. NICE promotes clinical and cost effectiveness through its technology appraisals, clinical guidelines and audit tools. NICE supports the work of those who make the complex treatment decisions - doctors, nurses, and other health professionals. The needs of the patient are central to NICE's work, and the Institute has forged strong links with patient groups and representatives.
   
21.

Topics for the NICE work programme are selected by the Department of Health and the National Assembly for Wales.
   
22. NICE advises the NHS on how these technologies can best be used. It is also responsible for the production of national clinical guidelines, promoting best practice throughout the NHS. To support and assess the implementation of such guidelines, NICE will produce audit tools for use in the clinical setting.