Chapter 5
Arthritis-Related Prescription Medications
Naomi Kasman, Elizabeth Badley
Introduction
Arthritis is a complex disease with no known cure. As
a result, treatment involves a wide variety of medications aimed at
relieving pain, preserving joint function and limiting progression
of the disease.1,2 Without effective treatment, arthritis
can lead to joint destruction, often resulting in long-term disability.
Current medications for treating arthritis include non-steroidal anti-inflammatory
drugs, low-dose corticosteroids, disease-modifying anti-rheumatic drugs,
and the newly available biologic response modifiers.2
Types of Arthritis-related Medications
For patients with arthritis and related conditions, non-steroidal
anti-inflammatory drugs (NSAIDs) form the basic component of
care.2-4 There are two categories of NSAIDs: conventional,
and the more recently developed COX-2 inhibitors. Conventional
NSAIDs effectively treat the pain and inflammation caused by arthritis,5 but
with long-term use they may lead to a variety of toxic side effects,
including gastrointestinal, liver or renal injury, heart failure
and adverse reproductive outcomes.3,6-8 COX-2 inhibitors
minimize the risk of stomach ulcers that occur with conventional
NSAIDs.9 Two COX-2 inhibitors were released onto the Canadian
market in 1999 - celecoxib (Celebrex™) and rofecoxib (Vioxx®),
and these drugs have proven as effective as conventional NSAIDs in
decreasing pain and inflammation but without the same degree of toxic
side effects. Their toxicity profile is still far from benign, however,
and is undergoing further research.
For nearly 50 years, corticosteroids have successfully
treated rheumatic diseases.10 Orally administered corticosteroids
help to temporarily reduce pain and inflammation in joints, and they
may help to increase joint mobility and function.2 When
other treatment methods do not work quickly or effectively enough,
injecting corticosteroids directly into an affected joint can reduce
severe, persistent inflammation. Corticosteroid injections result in
few adverse effects when the number of injections per joint is limited
to four or fewer per year.11
Disease-modifying anti-rheumatic drugs (DMARDs)
are used primarily to prevent the progression of rheumatoid arthritis
rather than merely treat the symptoms of the disease.1 Early
treatment of rheumatoid arthritis with DMARDs has proven to be very
effective in preventing lasting bone and joint damage, which, if left
untreated, may result in loss of function.1,12 DMARD therapy
is recommended as the primary treatment for rheumatoid arthritis, although
severe side effects continue to concern clinicians.
Biologic response modifiers (biologics) are a
new category of medication for treating inflammatory conditions such
as rheumatoid arthritis and for preventing disease progression. Biologics
work much more quickly than DMARDs: patients may begin to notice an
improvement in their arthritis within a few days to a week. Three biologics
are currently available in Canada - etanercept (EnbrelTM),
infliximab (RemicadeTM) and anakinra (KineretTM).
However, treatment with these drugs is very expensive. Annual
drug costs per patient treated with infliximab or etanercept are estimated
at over $12,500(USD), with total treatment costs at approximately $18,000
(USD) for infliximab and $12,600 (USD) for etanercept.13 As
these drugs have only recently been released onto the market, the relevant
data are not yet available for inclusion in this report.
Although all of the above drugs are used in the treatment
of arthritis and related conditions, many treat other conditions as
well. For example, cyclosporine was originally used to prevent rejection
following organ transplantation, chloroquine can be used to treat malaria,
and methotrexate was designed as a cancer treatment.
Methods
Arthritis-associated medications - namely the major
categories of NSAIDs, corticosteroids and DMARDs - were identified
through a review of the literature and in consultation with both a
rheumatologist and pharmacologist. For the list of drug names and categories
that were included in all analyses see Table 5A-1 in the Appendix at
the end of this chapter. While simple analgesics such as acetaminophen
(Tylenol®) and acetylsalicylic acid (Aspirin®)
are used for a wide range of musculoskeletal conditions, they are also
used for other, non-rheumatic conditions, and their purchase does not
require a prescription. As a result, they have not been included in
this report.
Drug Identification Numbers (DINs)
Health Canada's Therapeutic Products Directorate assigns
a unique Drug Identification Number (DIN) to every drug product that
it approves for use in Canada. Using Health Canada's Drug Product Database
(DPD), the DINs for all arthritis-related prescription medications
were determined. In addition to the DIN, the DPD provides product information,
including brand name, company name, ingredients, route of administration,
pharmaceutical form, therapeutic classification and packaging information.
The DPD is updated weekly.
The DINs from the DPD were organized into four drug
categories: conventional NSAIDs, COX-2 inhibitors, corticosteroids,
and DMARDs. Participating provinces used this set of DINs to obtain
the number of individuals who had received prescriptions for these
drugs. For this report, the number of total prescriptions was included
regardless of the associated diagnosis, for which data were not available.
Provincial Drug Plans
Provincial drugs plans differ in a number of ways, including
the portion of the population that is covered and the drugs that are
included in their formularies. Generally, all plans cover provincial
residents over the age of 65, low-income individuals (such as beneficiaries
of social assistance/welfare) and residents of long-term care facilities.
Further details of the various plans are available in Table 5A-2 in
the Appendix at the end of this chapter.
When considering provincial variation in the proportion
of individuals with prescriptions, the differences between the various
provincial drug plans must be taken into account. For example, the
very low percentage of prescriptions for COX-2 inhibitors in British
Columbia may reflect the strict regulations of the province's drug
plan.
Provincial drug plans differ in other notable ways as
well. Two provinces, Alberta and Ontario, report data only for individuals
over the age of 65 years. While Alberta Health & Wellness has plans
for groups other than seniors, only seniors' data are presented here
since they represent the entire population of seniors. Other plans
in the Alberta program are not population-based. Ontario's drug plan
generally covers only individuals over the age of 65, and data were
available only for this age group.
Data from Quebec included only prescriptions for individuals
with a diagnosis of a musculoskeletal condition given during the previous
year. For this reason, Quebec data are presented in a separate table
since the other provinces provided data for their entire populations.
Results
Provincial Time Trends for Arthritis-associated
Prescription Drugs
Charts displaying the provincial time trends for arthritis-associated
prescriptions are displayed separately for those under the age of 65
and for those 65 and over. Data were available from the majority of
provinces for the years 1994 to 2000. However, Alberta was unable to
provide drug data prior to 1996, since Alberta Blue Cross, its drug
plan administrator, did not have a unique patient identifier on its
system prior to this time.
Despite many differences between the provincial drug
programs and subsequent differences in the actual number of prescriptions
dispensed, the prescribing patterns for arthritis-associated medications
over time remained fairly similar across the country.
Non-steroidal anti-inflammatory drugs
Provinces showed similar patterns over time in the percentage
of individuals with prescriptions for conventional NSAIDs. The pattern
consisted of either a plateau or slight decline from 1994 to 1998 followed
by a larger drop between 1998 and 2000 (Figures 5-1 and 5-2).
This more recent decrease likely reflects the release of COX-2 inhibitors
onto the Canadian market in 1999. The decline in the percentage of
individuals with NSAID prescriptions before 1998 may be associated
with the availability of certain NSAIDs without a prescription as of
1996.
Once COX-2 inhibitors were released onto the Canadian
market in 1999, prescriptions written for these medications increased
quickly. The percentage of individuals with prescriptions for COX-2
inhibitors varied widely by province in 2000 (Figure
5-3). The extremely low rate of COX-2 inhibitor prescriptions in
British Columbia and the minimal decline in its conventional NSAID
prescriptions between 1998 and 2000 (Figure 5-2)
attest to the policy of the province's drug plan to cover COX-2 inhibitors
only under exceptional circumstances. In these “exceptional circumstances”,
COX-2 inhibitors are only available through special authority to patients
who fail to benefit from or who have adverse drug reactions to acetaminophen,
enteric-coated Aspirin, naproxen, ibuprofen and at least three other
funded NSAIDs.
Figure 5-1 Percentage of individuals aged 15 to 64 years with
prescriptions for conventional NSAIDs in five provinces, Canada,
1994-2000
* Not covered by drug formulary.
Figure 5-2 Percentage of individuals aged 65 years and over
with prescriptions for conventional NSAIDs in five provinces, Canada,
1994-2000
Figure 5-3 Percentage of individuals aged 65 years and over with
prescriptions for COX-2 inhibitors in five provinces, Canada, 2000
In Saskatchewan as well, unrestricted coverage of COX-2
inhibitors began only in mid-2000. Before this, individuals could receive
COX-2 inhibitors only if coverage was requested by a physician and
approved by the provincial drug plan.
Corticosteroids
The percentage of individuals under the age of 65 with
prescriptions for corticosteroids showed very little change between
1994 and 2000 (Figure 5-4). With the exception
of British Columbia, the percentage of those over the age of 65 showed
a slight increase between 1994 and 1998 (Figure 5-5).
Between 1998 and 2000, all provinces showed a decrease or remained
relatively constant.
Figure 5-4 Percentage of individuals aged 15 to 64 years with
prescriptions for corticosteroids in five provinces, Canada, 1994-2000
* Not covered by drug formulary.
Figure 5-5 Percentage of individuals 65 years and over with
prescriptions for corticosteroids in five provinces, Canada, 1994-2000
Disease-modifying anti-rheumatic drugs
Despite differences among the various provinces' drug
plans, the pattern of prescriptions for DMARDs has followed a remarkably
similar pattern across the country over time. Between 1994 and 2000,
in all age groups, the percentage of individuals who received prescriptions
for any DMARD rose consistently (Figures 5-6 and 5-7).
The fairly large increase in Ontario rates between 1996 and 1998 may
in part reflect the inclusion of the commonly prescribed medication
Methotrexate in that province's drug benefit formulary in 1997.
Figure 5-6 Percentage of individuals aged 15 to 64 years with
prescriptions for DMARDs in five provinces, Canada, 1994-2000
* Not covered by drug formulary.
Figure 5-7 Percentage of individuals 65 years and over with
prescriptions for DMARDs in five provinces, Canada, 1994-2000
Table 5-1 Number
and percentage of NSAID, corticosteroid, and DMARD prescriptions
for individuals with at least one musculoskeletal (MSK) diagnosis
during the previous year, Quebec, 1998 |
| |
Number
of Prescriptions Written for Individuals with a Diagnosis of
an MSK Condition During the Previous Year |
Percentage
of Prescriptions Written for Individuals with Specific MSK
Conditions |
Osteo- arthritis |
Rheumatoid Arthritis |
Any Other Arthritis |
NSAIDs |
220,020 |
23.4 |
4.5 |
50.5 |
Corticosteroids |
123,382 |
29.8 |
8.2 |
45.7 |
DMARDs |
10,711 |
16.9 |
58.5 |
17.3 |
Source: drug claims data from Regié de
l'assurance du Québec (RAMQ) |
Prescriptions and Associated Diagnoses
Unlike the other provinces, Quebec provided prescription
data only for individuals who had had a diagnosis of a musculoskeletal
(MSK) condition during the previous year.
In 1998, over 220,000 prescriptions for NSAIDs were
written in Quebec for individuals who had been given an MSK diagnosis
during the previous year. Conventional NSAIDs, which include the commonly
prescribed drug ibuprofen, are used to treat a wide variety of painful
joint conditions such as fibrositis, synovitis and traumatic arthritis,
many of which are included under the “any other arthritis” category.
Corticosteroids are also fairly widely used to treat painful joints,
and over 46,000 individuals (38%) in Quebec who had an osteoarthritis
or a rheumatoid arthritis diagnosis also were given prescriptions for
these medications. Of the 10,711 prescriptions for DMARDs that were
written for individuals with a musculoskeletal diagnosis in Quebec,
over three-quarters were prescribed to those with osteoarthritis (16.9%)
or rheumatoid arthritis (58.5%).
Discussion
Since arthritis has no known cure, current drug therapies
aim to minimize pain, preserve joint function and limit disease progression
by reducing inflammation. Chapter 5 has discussed three of the four
main categories of drugs for treating arthritis: NSAIDs (conventional
and COX-2 inhibitors), corticosteroids and DMARDs. The fourth, biologics,
is the newest category of arthritis drugs. According to early research,
biologics show promise for halting the progression of rheumatoid arthritis
and other forms of inflammatory arthritis.
New drugs for osteoarthritis, including drugs to prevent
progression in the early stage of the disease and disease modifying
drugs for established osteoarthritis, are currently on the horizon.
The availability of these drugs will increase the pool of people for
whom drug treatment is appropriate. Currently, only a small proportion
of people with osteoarthritis have prescription medication recommended
as a first line treatment.
Chapter 5 has presented data on prescribing patterns
of arthritis-related medications in five Canadian provinces. These
patterns have varied across both time and provincial jurisdiction.
Some of the increases and decreases in prescriptions may be the result
of changes in the provincial drug plan formularies over time. These
provincial differences raise concerns about inequities in access, in
terms of both age and availability of drugs. Results from this chapter
have been obtained only from the analysis of provincial drug program
databases. Many individuals may have private coverage provided by their
employers. As well, individuals may be prescribed any medication and
pay for it themselves.
The percentage of people with prescriptions for DMARDs,
the primary therapy recommended for rheumatoid arthritis, has increased
consistently over time.14 Nevertheless, the overall rate
of provision of these drugs falls well short of the estimated prevalence
of rheumatoid arthritis. In each of the provinces examined, the percentage
of the population aged 65 years and older that had a DMARD prescription
in 2000 was approximately half the estimated prevalence of rheumatoid
arthritis for this age group.15
In recent years, the efficacy of new prescription medications
used to treat arthritis, such as the biologics, has greatly increased.
This increase has been accompanied by an even larger increase in the
cost of such medications. In Ontario, for example, arthritis-related
prescription medications cost more than $70 million in 2000, almost
double the 1999 cost of approximately $37 million. The new biologics
will further increase this.
In 1998, the total economic burden of arthritis and
rheumatism in Canada was estimated to be $4.4 billion. The direct economic
costs (such as hospitalization and medications) were far less than
the indirect costs of lost wages and lost productivity due to disability.13,16 In
fact, the total cost of drugs, including management of the effects
of drug toxicity, constituted only 15% to 20% of the direct costs of
arthritis.13,16 Given the considerable economic burden of
arthritis, drug therapy has the potential for significant economic
benefit,16,17 especially if such therapy can be shown to
reduce the costs associated with disability, loss of productivity and
premature mortality.
This report demonstrates that regardless of provincial
differences, changes in the management of arthritis through medication
have occurred over the past decade. At the time of this report, data
are not available on the recently developed biologic response modifiers,
which were designed specifically for the treatment of arthritis.
Implications
Provincial variations in the provision of arthritis-related
drugs have been identified in this chapter.
Access to arthritis medications that have proven to
be effective in preventing joint damage is a key issue. This includes
access to DMARDs as well as the newly developed biologic drugs.
Drugs have the potential to reduce long-term economic
and social costs of arthritis-related disability. Ensuring effectiveness
through pharmaco-economic analysis of new arthritis drugs would help
ensure that this potential is realized.
Surveillance of arthritis and related conditions should
include the monitoring of changes in health status or health care utilization
that may be related to drug therapy. Monitoring should consider both
adverse effects and potential benefits, such as changes in mortality
or hospitalization for gastrointestinal bleeding since the introduction
of COX-2 drugs.
For future surveillance purposes, linking prescription
data to patient diagnoses would result in better examination of prescribing
patterns for arthritis and related conditions.
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