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
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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