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Osteoarthritis "Opportunities To Address Pharmaceutical Gaps"
Osteoarthritis "Opportunities To Address Pharmaceutical Gaps"
12: Osteoarthritis
Priority Medicines for Europe and the World
"A Public Health Approach to Innovation"
Background Paper
Osteoarthritis
Opportunities to Address Pharmaceutical Gaps
6.12-1
6.12: Osteoarthritis
Table of Contents
Summary..............................................................................................................................................3
1.
Introduction..........................................................................................................................4
2.
3.
Control Strategy....................................................................................................................8
4.
5.
6.
7.
8.
9.
Conclusion..........................................................................................................................22
10.
References............................................................................................................................23
Annexes
6.12-2
6.12: Osteoarthritis
Summary
Osteoarthritis (OA) is the most common type of arthritis or degenerative joint disease. 1 It is a
leading cause of chronic disability. The disease most commonly affects the middle-aged and
elderly, although younger people may be affected as a result of injury or overuse. Age is the
strongest predictor of the disease and therefore increasing age and extended life expectancy
will result in a greater occurrence of the disease. Patients affected by this disease suffer from
pain and loss of function.
OA is regarded as a complex disease whose cause is not completely understood.
Furthermore, effective biomarkers, diagnostic aids and imaging technology are not available
to assist in the management of OA. There are also several areas where information is still
lacking; these include: epidemiology, pathophysiology, environmental risk factors, genetic
predisposition and lifestyle factors.2, 3
At present, there is no cure for OA. The management of OA is broadly divided into nonpharmacological, pharmacological, and surgical treatments. Surgical management is
generally reserved for failed medical management where functional disability affects a
patients quality of life. Pharmacological management includes control of pain and
improvement in function and quality of life while limiting drug toxicity. Experts in this field
suggest that appropriate therapy for OA combines one or more pharmacological agents with
exercise, weight loss and physical therapy (i.e. non-pharmacological therapy).
There are a number of drugs under development for symptomatic and disease modification,
and several studies are also evaluating alternative therapies. There are several drugs on the
market whose clinical effectiveness and long-term safety still need to be determined. This
assessment is especially important since OA requires long-term disease management and the
disease primarily affects people over the age of 60 who are most prone to drug toxicity, and
for whom the potential for drug interactions are high. Information on the impact of the
disease to society and the cost of disease management (including pharmacological and nonpharmacological treatments) needs to be re-evaluated. Finally, most experts emphasize that
more research efforts need to be directed towards new diagnostics, biomarkers and imaging
technology. This is an essential area of research in OA since it will help to determine who is
likely to get OA; severity and progression of disease; patient response to drugs, and the
development of disease modifying drugs that have the potential to halt or reverse the
disease.Error: Reference source not found, Error: Reference source not found
6.12-3
6.12: Osteoarthritis
1. Introduction
There are more than 100 different types of arthritis.Error: Reference source not found The
most common type of arthritis is osteoarthritis (OA) or degenerative joint disease. It is a
common chronic, progressive musculoskeletal disorder characterized by gradual loss of
articular cartilage. The disease most commonly affects the middle-aged and elderly, although
it may begin earlier as a result of injury or overuse. It is often more painful in weight bearing
joints such as the knee, hip, and spine than in the wrist, elbow, and shoulder joints. All joints
may be more affected if they are used extensively in work or sports, or if they have been
damaged from fractures or other injuries.Error: Reference source not found, 4
6.12-4
6.12: Osteoarthritis
Figure 1 Burden of disease of OA by age groups and regions
6.00%
% of total
5.00%
4.00%
3.00%
2.00%
1.00%
0.00%
0-4
5-14
15-29
30-44
45-59
60-69
70-79
80+
Age groups
EU25-M
EU25-F
EU15-M
EU15-F
EU-10-M
EU-10-F
W-M
W-F
Note from Figure 1, the peak in the burden of disease (DALYs) in each of the three
regions: Global, EU15, EU25, and EU10 are different. In EU 10, the onset of OA is at an
earlier age, perhaps resulting in more disability, loss of productivity and increased health
care costs.
Knee OA is likely to become the fourth most important global cause of disability in
women and eighth most important in men.Error: Reference source not found
OA contributes to a higher disease burden in men below the age of 50 and in women over
the age of 50.
According to expert opinions presented in the EULAR committee report, radiographic
evidence of knee OA in men and women over 65 is found in 30% of patients.Error:
Reference source not found
Figure 2 shows the prevalence of OA of the knee by age group, sex and region.Error:
Reference source not found In general OA is more prevalent in Europe and USA than in
other parts of the world.Error: Reference source not found
6.12-5
6.12: Osteoarthritis
Figure 2. Prevalence of osteoarthritisError: Reference source not found
Country impact
Aggregate numbers on the overall impact of OA are not available. Therefore, statistical
highlights and the impact of arthritis from individual countries that have reported
information are presented.
UKError: Reference source not found
In England and Wales between 1.3 and 1.75 million people have symptomatic OA. In 2000
more than 80,000 hip or knee replacements were performed at a cost of 405 million.
As a cause of disability (such as walking and climbing stairs) in the elderly OA is second
to cardiovascular disease.
Altogether 10% to 15% of adults over 60 have some degree of OA.
Germany6
Four million people out of 82 million people suffer from some form of autoimmune
conditions affecting joints.
Most people participate in a universal medical health insurance system.
The key issues in the fight against arthritis include access to medications, access to
speciality care, uncoordinated treatment, and diminished state budgets.
The direct and indirect costs of arthritis in Canada equates to approximately $18 billion
per year.
Over four million Canadians out of 31,014,000 people have arthritis.
6.12-6
6.12: Osteoarthritis
Currently there are approximately 270 rheumatologists in Canada; however, 150 of them
are close to retirement leaving 120 rheumatologists to care for 4 million suffering arthritis
patients.
There are approximately 37,000 hip and knee replacement surgeries every year in
Canada.
The key issues in the fight against arthritis facing Canada include: access to medications,
access to rheumatology care, access to orthopaedic care, funding for research and illness
disability.
US7, 8, 9
It is estimated that over 41 million people out of 285 million people in the United States
have arthritis.
In the United States about 6 percent of adults over 30 have OA of the knee and about
3 percent have OA of the hip.
The occurrence of the OA increases with age, rising 2- to 10-fold in people from 30 to
65 years of age.
An estimated 50 million people will be diagnosed with arthritis by 2013.
The current economic burden of arthritis in its various forms is approximately
$82.4 billion.
Direct costs are $34.6 billion (hospitals, doctors, transportation, nursing homes)
Only 3% of the cost is for drugs.
Indirect costs are $47.8 billion (primarily lost wages and lost productivity).
Arthritis is a greater factor in limiting activity than heart disease, hypertension,
blindness, or diabetes. Figure 3 shows the levels of physical activity reported by women
with arthritis in the US. Only 24% of people with arthritis report and achieve levels of
physical activity that are recommended for health. The remainder are essentially inactive
or insufficiently active.
6.12-7
6.12: Osteoarthritis
Figure 3. Levels of physical activity reported by women with arthritis in the US 10,
Error:
3. Control Strategy
Patients with OA suffer from pain and loss of function. Objectives of OA management are to
reduce the level of pain, reduce inflammation, slow cartilage degradation, improve function
and reduce disability. This section reviews pharmacological and nonconventional, nonpharmacological OA therapies.
Diagnosis and medical management Error: Reference source not found, Error: Reference source not found,
Error: Reference source not found, Error: Reference source not found, Error: Reference source not found, 11, 12, 13
6.12-8
6.12: Osteoarthritis
The management plan of OA patients also needs to be regularly reviewed and adjusted in
light of their response and adherence. This will vary between patients and location.
The management of OA is broadly divided into non-pharmacological, pharmacological,
and surgical treatments. Surgical treatment is generally reserved for failed medical
management with functional disability affecting a patients quality of life.
Prevention
Preventing the onset of OA requires lifestyle changes.Error: Reference source not found, 14
Primary prevention. These are measures to prevent the condition from occurring. There are
only a few effective primary prevention strategies for arthritis. These include:
Weight control: Obesity is considered a risk factor for OA. Thus, maintaining or
reducing weight can lower the risk for certain arthritic conditions.
Occupational injury prevention: Avoiding repetitive joint use and its injuries can
help prevent arthritis.
Sports injury prevention: Taking the necessary precautions to prevent injury such
as warming up and using proper equipment can help reduce joint injuries.
Secondary prevention. This involves early diagnosis so that appropriate early intervention
can be utilized. However, this is difficult in OA since no effective biomarkers are
available to determine the progression of the disease. Furthermore, radiographic
evidence is often needed to identify and mark disease progression. Access to health care
facilities and availability of X-rays is problematic in many parts of the world.Error:
Reference source not found, 15
Tertiary prevention. This focuses on reducing the consequences of a disease. Goals of these
prevention strategies are to reduce, delay the onset of complications and disability.
Tertiary prevention strategies for arthritis are aimed at reducing pain and disability, and
improving quality of life. The following encompass tertiary prevention strategies: selfmanagement (weight control, physical activity, education); home help programs;
cognitive behavioural interventions; rehabilitation services and medical surgical
treatments.Error: Reference source not found
6.12-9
6.12: Osteoarthritis
Table 1. Therapeutic options in osteoarthritis Error: Reference source not found, Error: Reference source not found, Error:
Reference source not found, Error: Reference source not found, 16, 17
Non-pharmacological treatment
Education (patient and spouse or family)
Social support
Physiotherapy (physical therapy)
Occupational therapy
Weight loss
Exercise
Orthotic devises
Laser
Pulsed EMF (Electromagnetic field therapy)
Ultrasound
Transcutaneous electrical nerve stimulation (TENS)
Acupuncture
Nutrients
Herbal remedies
Vitamins/minerals
Pharmacological treatment
Paracetamol/Acetaminophen
NSAIDS (Non-steroidal anti-inflammatory drugs) [plus misoprostol or a proton
pump inhibitor]*
COX-2 inhibitors (cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drugs)
Opioid analgesics
Hormones
Psychotropic drugs [comment- can this be elaborated using a couple of examples?
These are also not covered in pharmacological treatment sections below]
SYSADOA (Symptomatic Slow Acting Drugs for OA (avocado/soybean
unsaponifiables (ASU), chondroitin, diacerein and glucosamine)
Topical NSAIDS
Topical capsaicin
Intra-articular treatment
Corticosteroids
Hyaluronans
Tidal irrigation
Surgical
Arthroscopy
Osteomy
UKR (unicompartmental knee replacement)
TKR (total knee replacement)
*Misoprostol and proton pump inhibitors are recommendations by ACR and are
recommended in patients who are at increased risk of gastrointestinal adverse effects.
6.12-10
6.12: Osteoarthritis
Non-pharmacological therapy review
According to various recommendations, non-pharmacological treatment of OA should
include education, exercise, physical aids (such as canes, insoles and knee braces) and weight
reduction.Error: Reference source not found, Error: Reference source not found
EducationError: Reference source not found, Error: Reference source not found
ExerciseError: Reference source not found, Error: Reference source not found, 18
Weight lossError: Reference source not found, Error: Reference source not found, Error: Reference source not found
Although weight loss is recommended, the effect of weight loss on OA has only been
evaluated in two studies. These studies showed that weight loss reduced the risk of
developing symptomatic OA in women, reduced pain and improved function. Most
authors conclude that while the evidence is poorly documented weight loss is a sensible
recommendation in the management of OA.
Physical aidsError: Reference source not found,Error: Reference source not found
There is limited data on the effects of physical aids on OA, although, physical aids are
considered a sensible approach in the management of OA.
A BMJ Clinical review concluded that RCTs in people with knee OA found limited
evidence that joint bracing or taping improves quality of life and symptoms. The review
also found that there was insufficient evidence to compare the effects of different insoles.
6.12-11
6.12: Osteoarthritis
adverse effects are common and the long-term efficacy of these drugs is variable or yet to be
determined.Error: Reference source not found, Error: Reference source not found, 19
Annex 6.12.1 provides a detailed analysis on the current effectiveness of medical
management of OA.
Below are the summarized highlights of the literature findings.
Analgesics- paracetamol/acetaminophenError: Reference source not found, Error: Reference source not
found, Error: Reference source not found, 20
Both the American College of Rheumatology (ACR) and European League Against
Rheumatism Guidelines (EULAR) recommend paracetamol/acetaminophen as the first
list line agent. EULAR recommendations also state that based on it overall cost, efficacy
and toxicity profile, it should be the preferred long-term oral analgesic.
A BMJ clinical evidence review found limited evidence that simple analgesics such as
paracetamol, reduced pain compared with placebo. However, a review by EULAR
reports that paracetamol is as effective as NSAIDS in the management of OA.
Furthermore, it can be taken safely over the long term.
A recent study has also raised concern about the safety of acetaminophen in doses of
greater than 2g/day. The study suggests that high dose acetaminophen may results in an
increased risk of gastrointestinal toxicity equivalent to NSAIDs.Error: Reference source
not found, 21
Non-steroidal anti-inflammatory drugs (NSAIDs) Error: Reference source not found, Error: Reference
source not found, Error: Reference source not found, Error: Reference source not found, Error: Reference source not found, Error: Reference source not found
NSAIDs have both anti-inflammatory and analgesic properties, but there is no evidence
that they modify the course of OA.
There is limited evidence that these agents vary in efficacy within this therapeutic drug
category.
According to systematic reviews conducted by BMJ, NSAIDs are more effective than
placebo in reducing pain; however, their long-term efficacy (past 2 years) has not been
studied. Also, systematic reviews of RCTs by BMJ, found no good evidence that oral
NSAIDS differ from paracetamol/acetaminophen in pain relief.Error: Reference source
not found
According to the 2003 EULAR review, the expert committee states that there is evidence
that NSAIDs are more efficacious than paracetamol for some patients. The
recommendations suggest that given the low-grade inflammatory component of OA,
NSAIDs would be the logical drugs in patients unresponsive to paracetamol.Error:
Reference source not found
Risk factors for NSAID-induced upper gastrointestinal adverse effects include: patients
greater than 65 years, concomitant use of anticoagulants and glucocorticoids and history
of peptic ulcer disease or upper gastrointestinal bleed, smoking and alcohol
consumption.Error: Reference source not found, 22
- In the US an estimated 20% to 30% of all hospitalisations due to peptic ulcer disease
are secondary to NSAID use.Error: Reference source not found
- Gastroduodenal ulcers occur in 15% to 30% of patients who take NSAIDs.Error:
Reference source not found
6.12-12
6.12: Osteoarthritis
Another serious complication associated with NSAIDS includes renal failure. Risk factors
for renal failure include: age greater than 65, hypertension, congestive heart failure,
concomitant use of diuretics, concomitant use of angiotensin-converting enzyme
inhibitors, and existing renal failure.Error: Reference source not found , Error: Reference source not
found
6.12-13
6.12: Osteoarthritis
Cyclooxygenase-2 (COX-2) InhibitorsError: Reference source not found , Error: Reference source not found,
Error: Reference source not found,Error: Reference source not found, Error: Reference source not found
COX-2 inhibitors have been found to be more effective than placebo in relieving pain in
OA.Error: Reference source not found, Error: Reference source not found
This class is just as efficacious as NSAIDs for pain relief but with a reduction of up to 50%
in perforation, ulcers and bleeding.Error: Reference source not found
There are reports that the cardiovascular and renal adverse effects are comparable to
NSAIDs and the risk factors associated with renal failure are the same as NSAIDs (listed
above).Error: Reference source not found
Concern about loss of antiplatelet activity with COX-2 inhibitor group may contribute to
excess cardiovascular complication, especially in the elderly who are at a higher risk of
cerebral and vascular thrombosis.Error: Reference source not found
Concomitant use of low dose aspirin for cardiovascular prophylaxis appears to diminish
COX-2 inhibitor gastroprotective effect.
There are no RCTs to compare the efficacy of different COX-2 inhibitors.Error: Reference
source not found
Haq et al report that the estimated cost of switching high-risk patients with OA to COX-2
inhibitors would lead to an estimated incremental cost of 25 million to the NHS.Error:
Reference source not found
COX-2 inhibitors are widely used in the US and Europe, and are currently block buster
drugs on the pharmaceutical market, however the most cost effective strategy for their
use is still unclear.Error: Reference source not found
Both ACR and EULAR state that patients who are at an increased risk of gastrointestinal
complications, COX-2 inhibitors or NSAIDs plus a gastroprotective agent may be
used.Error: Reference source not found, Error: Reference source not found, Error: Reference source not found
Topical agentsError: Reference source not found, Error: Reference source not found, Error: Reference source not found
According to ACR and EULAR guidelines, topical NSAIDs and topical capsaicin have
clinical efficacy and are safe.
BMJ clinical review concludes that topical NSAIDs reduce pain compared to placebo,
however limited evidence was found that capsaicin improves pain compared to placebo.
Topical treatment is an additional option for patients who have inadequate control with
oral agents or who require local treatment. However, further well-conducted trials are
needed in this area.
Intra-articular, long acting corticosteroids are widely used in the management of knee
OA.
The short-term therapy is considered to be beneficial in patients who have local
inflammation and swollen joints.
Injections may be used as monotherapy or in combination with systemic drugs.
There are no RCTs comparing the effectiveness of combination therapy.
Most review articles that have evaluated intra-articular corticosteroids studies conclude
that there appears to be a short-term efficacy lasting 2-4 weeks compared to placebo.
6.12-14
6.12: Osteoarthritis
A systematic review and one RCT found limited evidence that intra-articular
corticosteroids reduced pain for 1-4 weeks.
There is evidence that intra-articular injections are effective with short-term relief.
However, the evidence for predictors of response remains unclear and further studies are
needed to determine this.
ACR guidelines recommend no more than 3- 4 injections per year and should be reserved
for disease flares only.
Infection into the OA joint is considered to be a rare complication associated with this
intra-articular corticosteroid therapy.
Current recommendations are to use intra-articular steroids when other analgesics and
NSAIDs are ineffective or contraindicated.
6.12-15
6.12: Osteoarthritis
the long-term effects and safety of these drugs.Error: Reference source not found,
Error:
6.12-16
6.12: Osteoarthritis
Long L et al, conducted a systematic review of herbal medicines for the treatment of
osteoarthritis. Studies in the review examined: articulin F, capsaicin cream, devils claw,
eaymov, gitadyl, phytodolor, reumalex and stinging nettle leaf.
Promising evidence was found for the effective use of some herbal preparations in the
treatment of OA. Also, there is some evidence that these preparations may reduce the use
of NSAIDS. Furthermore, the reviewed herbal medicines appear to be safe.Error:
Reference source not found, Error: Reference source not found
The area of herbal medicines in OA is under-researched and merits further attention.
Future trials should focus on clinical effectiveness of herbal therapies, outcome measures
and valid measures of OA. Studies should also compare and assess the impact of herbals
medicines on allopathic medication, specifically NSAIDs.Error: Reference source not
found, Error: Reference source not found
A number of alternatives exist for the treatment and prevention of OA. Some of these
include Vitamin E, Boron, Vitamin D, Ascorbic acid, Manganese, S-Adenosylmethionine,
Avocado/Soybean extract and Articulin F. Very limited evidence is presented on the
safety and effectiveness of these agents and further well-conducted studies are
needed.Error: Reference source not found
Surgical treatment
Surgical treatment of osteoarthritis is usually considered after failure of nonsurgical
therapies. There are four surgical procedures: osteotomy, arthroscopy, arthrodesis and
arthroplasty. The four procedures have different indications and variable benefits. Total joint
arthroplasty, the most surgically advanced in OA treatment, is the mainstay of surgical
treatments.Error: Reference source not found Total joint replacement is highly successful and
by most measures among the most effective of all medical interventions. Pain, and disability
of end-stage OA can be eliminated, restoring patients to near-normal function, and this
operation is highly cost-effective.Error: Reference source not found The most common
failures of total joint replacement surgery include aseptic loosening and osteolysis, which
occur as a result of the corrosion between the implanted material and the cells.Error:
Reference source not found Currently there are no RCTs, which have compared surgery with
nonsurgical intervention. Although EULAR acknowledges the difficulties in study design,
the expert committee recommends that predictors of response, indications for joint
replacement, effect of different surgical techniques and long-term effect of joint prosthesis
should be examined. Furthermore, postoperative care and outcome assessment should also
be studied for these procedures.Error: Reference source not found
Affordability, feasibility and sustainability
Limited literature is available on the affordability, accessibility and cost of currently approved
therapies and their impact and management of OA. Further studies are required to address
this issue. Studies need to asses (1) the cost of drug therapy for disease management and (2)
the combination of non-pharmacological and pharmacological treatment modalities.
The economic implications of arthritis include the financial burden of health care costs,
and loss of income resulting from disability or limitations on work. Arthritis is ranked
second, after heart disease, as a cause of missed work in the developed world.Error:
Reference source not found
6.12-17
6.12: Osteoarthritis
Economic indicators for OA are difficult to develop. This is because data can be collected
on the medical resources (which is dependent on cultural, economics, and health care
provisions), than on the condition itself. Also, while lost days of work may be
determined, a large population affected are elderly and not working.
The estimated health-care cost of OA was US $624 million in 1993-94. This is
approximately 21% of the total musculoskeletal disorders expenditure.Error: Reference
source not found
The total cost, treatment, complications and the disability that result from arthritis is
estimated at $65 billion. Of this, the estimated medical costs are $15 billion annually,
which include physician visits and hospitalisations. The remaining balances are indirect
costs resulting from wage losses.Error: Reference source not found
6.12-18
6.12: Osteoarthritis
Risk factor
Genetics
Obesity
Diet
Bone density
Trends
Increasing age and extended life expectancy will most likely result in greater incidence
and prevalence of OA. The burden will be greatest in developing countries where life
expectancy is increasing, but access to therapy is not readily available.Error: Reference
source not found, Error: Reference source not found
6.12-19
6.12: Osteoarthritis
shown to play an important role in chondrocytes activity. Hence, these molecules have
also become a potential target for pharmacological intervention and studies of such
agents are planned or ongoing.Error: Reference source not found, Error: Reference source not found, 36
Bisphosphonates. Resorptive agents or bisphosphonates (such as alendronate and
clodronate) may provide important benefits in the symptomatic relief of OA. Initial
results of the studies have not been made available yet. Also, this class of drugs are not
clinically approved for OA therapy.Error: Reference source not found
Growth factors. Growth factors are being evaluated in the management of OA and its affect
on cartilage.Error: Reference source not found, Error: Reference source not found Refer to Annex 6.12.
for more information.
Alternative medicines: The US Congress created The National Center of Complementary
and Alternative Medicine (NCCAM) given the growing use of alternative medicines.
Currently NCCAM and the National Institute of Health (NIH) are supporting a large
RCT evaluating the effectiveness of glucosamine and chondroitin in the treatment of
OA.Error: Reference source not found
462795
(Cathepsin K
inhibitor)
ABT 963
CP-544,439
ML-3000
Pennsaid
Topical
Osteoarthritis
Osteoporosis
Cathepsin K is believed to play a role in
degrading bone. 38
Cathepsin K inhibitors have the potential to
provide a new therapeutic agent for the
treatment of OA.39
Osteoarthritis
Rheumatoid arthritis
ABT 963 is a COX-2 inhibitor like celecoxib
and rofecoxib already on the market. The
drug is intended for the symptomatic
treatment of OA40.
Osteoarthritis
No available information
Osteoarthritis
A new class of anti-inflammatory and
analgesic drugs. Also known as COX/LOX
inhibitors. This class are inhibitors of both
cyclooxygenase and leukotrienes and have the
potential to reduce gastrointestinal toxicity.41, 42
Osteoarthritis
Rheumatoid arthritis
6.12-20
Company
Development
status
GlaxoSmithKline
Phase I
Abbott
Laboratories
Phase II
Pfizer
Phase II
Forest
Laboratories
Phase III
Dimethaid
Research
Application
submitted to
6.12: Osteoarthritis
Investigational
drug name
Solution
Pralnacasan
Various COX-2
inhibitors
Company
FDA
6.12-21
Development
status
Aventis
Pharmaceuticals
Various
companies
Phase II
6.12: Osteoarthritis
7. Opportunities for Research into New Pharmaceutical Intervention
See Annex 6.12
The area of drug development in OA is of a significant public health consequence. Current
therapies on the market only help to improve pain and function. There are no drugs that can
prevent, reverse or halt the disease. Several questions remain unanswered in the areas of
epidemiology, pathophysiology and diagnosis of the disease. These need to be studied to
support the effective development of novel disease modifying agents. There are also a large
number of drugs (including alternative therapies, vitamins, and nutraceuticals) whose
clinical effectiveness still needs to be determined through better-conducted clinical trials. The
following are highlights for opportunities for research in OA as put forward by various
expert members on ACR and EULAR and authors:
These studies bridge the range of research from basic science to Phase IV studies.
6.12-22
6.12: Osteoarthritis
-
Complementary and alternative medicines are of great interest to consumer groups affected
with OA.Error: Reference source not found In the US, complementary and alternative
medicines are the most rapidly growing area at the NIH (National Institute of Health). There
is substantial research opportunity potential in this area.46
While exciting breakthrough treatments continue to become available for rheumatoid
arthritis, highly effective therapies do not exist for OA. Currently, the research to support
treatments in OA is not as advanced as compared to rheumatoid arthritis. Interestingly, it has
been discovered that the cytokines that are driving inflammation and destruction of bone
and cartilage in rheumatoid arthritis may also drive the destructive process in OA.Error:
Reference source not found This discovery may potentially be helpful since some of the
knowledge about rheumatoid arthritis may be transferred and applied to osteoarthritis.
Furthermore, with better understanding through research of the molecular process, progress
may be achieved in the development of medications to effectively control the symptoms and
disease progression of OA as well.Error: Reference source not found
The following are areas that need research:Error: Reference source not found, Error: Reference source not
found
Strengthen evidence-based medicine by closing the gap between molecular research and
clinical disease research for OA.
Drug development in OA has been lacking, because in order to diagnose, monitor and
develop treatments for OA, researchers and drug companies require effective biochemical
and imaging markers to assess disease progression. Current evaluation methods of x-rays
and blood tests are insufficient to determine the progression and outcome of new
treatments. As a result, a recent US-based public private partnership, called the
osteoarthritis Initiative (OAI), intends to combine resources for the purpose of finding
biological markers related to the progression of OA. OAI will collect data over the next 57 years on individuals at high risk for the development of OA. This data will be used for
the development of potential new OA treatments. OAI is a combined effort in the US by
NIH (National Institute of Health), GlaxoSmithKline, Merck, Novartis Pharmaceuticals
Corporation and Pfizer. OAI will provide approximately 8 million dollars annually to six
clinical research centres to establish and maintain a database of OA, which will include
evaluation data, radiological images and a biospecimen repository. All the data will be
available to researchers worldwide.47
Inter country differences: Certain drugs are available in parts of Europe, whereas others are
not available in other countries or the US. The difference in the availability of drugs may
result in differences in clinical practice and level of patient expectation of OA drugs.
6.12-23
6.12: Osteoarthritis
Level of evidence of efficacy: Despite certain drugs being on the market for several decades,
such as ASU (Avocado/Soybean unsaponifiable) residues in France, their efficacy was not
determined until recently.25 The position of many recent health authorities has facilitated
improvement in the level of evidence and the observed treatment effect of drugs. On the
other hand, there are numerous unpublished studies. Emphasis on most peer review
journals is about the statistically significant effect of these treatments. To answer this and
to determine the level of efficacy, trials should compare the observed effect of new
treatments to conventional drugs such as NSAIDs.
9. Conclusion
The prevalence of OA is increasing and this places a globally major burden on individuals;
health systems, and social care systems. OA, the most common arthritis condition, is a major
cause of impaired mobility and disability for the ageing populations. While there are several
drugs available on the market that mitigate pain and improve function, there are no drugs
that can cure, reverse or halt disease progression. OA is also now regarded as a complex
disease whose etiology is not completely understood. In addition there are also several areas
where information is still lacking; these include epidemiology, path physiology,
environmental risk factors, genetic predisposition and lifestyle. Information related to these
topics may assist in the overall management and planning of this disabling condition. There
are a number of drugs in the pipeline under development and several studies also evaluating
alternative therapies. There are, however, several drugs on the market whose clinical
effectiveness and long-term safety still need to be determined. This is especially important
since OA requires long disease management and the disease primarily affects people over the
age of 60, who are most prone to drug toxicity. In addition, data is lacking about the
therapeutic effectiveness of certain drugs within a class as well as between classes.
Information on the impact of the disease to society and both the cost of medicines and cost of
disease management (including pharmacological and non pharmacological treatments) need
to be evaluated. Finally, while there is substantial research in this area, most experts
emphasize that research into new diagnostics, biomarkers and imaging technology is going
to be important and useful for the management of OA and the development of disease
modifying drugs.
6.12-24
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