|
Until recently most patients with early rheumatoid arthritis (RA) have been treated, initially, with nonsteroidal anti-inflammatory
agents or low doses of corticosteroids. Only those patients who had continued synovitis or who had extra-articular manifestations
of their rheumatoid disease were treated with one of several disease modifying agents (DMARDS). Because of the
potential adverse reactions of the DMARDS, and together with their considerable expense, these agents were usually used alone.
However, in the last few years, there has been increasing enthusiasm for the early institution of DMARD therapy and, even
more recently, for the use of early combination DMARD therapy.
The rationale for combination DMARD therapy soon after the diagnosis of RA is established is based upon several theoretical
considerations and clinical observations: Recent studies of the natural history of rheumatoid arthritis, using
a single DMARD, have emphasized the dire prognosis in a subset of RA patients who have a genetic predisposition (best identified
at present by the presence of a shared epitope in the variable region of the histocompatibility antigen HLA-DR), are seropositive
(rheumatoid factor positive), have early articular erosions, have functional disability early in the course of their disease
and who have elevated levels of CRP. In the early stages of RA, patients are generally healthier and, therefore,
better able to withstand the potential adverse effects of these drugs. Early in the course of RA, there is less
disease mass (i.e., proliferative synovitis) to suppress and less irreversible joint damage. The different DMARDS
appear to act at different sites in the immunological and inflammatory cascades. While rheumatologists have been aware of
the potential additional efficacy of combination DMARD therapy for some time, large prospective trials to test this therapeutic
possibility have been delayed by the success of methotrexate (MTX) as a single DMARD. More than 75% of rheumatoid
arthritis patients receiving weekly oral or parenteral MTX achieve a moderate to excellent response with a minimum of adverse
reactions requiring discontinuation of the MTX. However, as is the case with all of the currently used DMARDs, only
a few of these patients actually go into a complete remission. Thus, the MTX therapy must be continued and we are beginning
to see an increasing number of patients who are relapsing after several years of treatment with MTX. Another
reason for the delayed large scale implementation of early combination DMARD therapy has been the hope that the recently introduced
monoclonal antibodies to T helper lymphocytes would prove to be significantly better than the current DMARDS in the treatment
of RA. Unfortunately, several trials with these products of molecular biology have proved to be rather toxic and not particularly
effective. Most of the published trials using more than one DMARD have been confined to patients whose RA had
already failed to respond to one or more of these drugs used as single agents. As might be expected, in this subset
of difficult patients with well established disease, the results of these studies were not very promising. Only
very recently has combination DMARD therapy been compared with single DMARD therapy in prospective randomized studies of patients
who had not failed previous DMARD therapy. Some of these studies have indicated that early combination therapy may be both
more effective than single agents. In all of these trials, the toxicity from the combination therapy has been
quite low and comparable to that encountered with the single agents alone. No toxicity resulting from interaction between
the different DMARDs has been reported and no significant drug interaction has been observed. Three combinations
that appear to be promising are sulfasalazine (SSZ) plus MTX, cyclosporine A plus MTX, and SSZ plus MTX plus hydoxychloroquine
(HCQ). One of the goals of early combination DMARD therapy is the induction of a remission in the RA in a significant
number of patients, thereby permitting all anti-rheumatic therapy to be gradually withdrawn (sometimes referred to as step-down
therapy). This goal has clearly not been achieved in the trials reported to date. In view of the encouraging
results and the very low order of toxicity that has been observed, it would seem reasonable to study these combinations using
increased doses; or the addition of even more agents to the combinations in the hope of achieving early and lasting remissions
in these patients -- an approach not unlike that used in the chemotherapy of certain malignancies. While some
investigators ( many do ) may not feel that early combination DMARD therapy is a major break through in the treatment
of RA, they do believe that it is worth trying in some RA patients who have a poor prognosis at the onset of their disease
-- objective evidence of persistent proliferative synovitis involving several joints, significant functional disability on
a verified test such as the HAQ index, seropositivity and elevated levels of C reactive protein. The goal of
therapy in these patients is to eradicate all signs of synovitis and to bring the CRP down to normal. When carefully monitored,
these combinations appear to be quite safe and effective in certain patients.
ACR position on cost-new medications: Several new medications used to treat both inflammatory and degenerative arthritis
have been recently approved by the U.S. Food and Drug Administration. The need to balance the potential
benefit of rational and appropriate use of these newer therapies with their increased cost is of significant importance to
people with rheumatic diseases, their physicians, health insurance purchasers and third party payers. Following
double-digit health care inflation in the late 1980s and early 1990s health care premiums have been stable over the past few
years. However, despite the flat to declining health care premiums, the cost of providing medications has risen 15-18 percent
a year during this period. If this trend continues, it is estimated that over the next few years pharmaceutical costs will
overtake those associated with hospitalization. Several new arthritis therapies have been introduced, including
cyclo-oxygenase 2 (COX-2) inhibitors and new biologic and immuno suppressive agents. More new therapies, perhaps new
classes of drugs, are on the horizon.
Early studies suggest that some of these agents may surpass currently available treatments either due to improved
efficacy or a better side effect profile. COX-2 inhibitors may provide comparable relief to other non-steroidal
anti-inflammatory drugs (NSAIDs) with potentially less gastrointestinal toxicity. The new biologic and immunosuppressive
agents provide new or improved mechanisms to control inflammatory arthritis. These advances, however, are not without increased
costs. The new COX-2 inhibiting NSAIDs, may be several times more expensive than non-selective generic NSAIDs. New biologic
agents can cost $10,000 per year or more. Insurers, health delivery systems, and self-funded employers have
tried to control pharmacy costs by: Using formularies and other prescribing rules and restrictions. Increasing medication
copayments and creating differential pricing between generic and brand medications. Outsourcing management to pharmacy benefit
companies. Providing clinician feedback on prescribing patterns and associated costs. Creating treatment guidelines. Placing
the pharmacist or clinician at financial risk for medication costs Despite these efforts, medication costs continue
to rise. In our multifaceted system of private and public insurance coverage, both the cost burden and the potential benefit
of access to these new medications is often unevenly distributed. Fully capitated large multispecialty groups
may place the provider at risk for pharmacy costs. In contrast, in delivery systems where providers accept risk only for professional
services, the insurer or managed care organization (MCO) is primarily at risk for medication costs. Self-funded employers
and preferred provider organizations (PPOs) may be at risk for medication costs or may shift part or all of that risk by contracting
with a pharmacy benefit management company. Medicare beneficiaries are disproportionately impacted by
rising pharmacy costs. Medicare has generally not provided outpatient medication coverage, resulting in many Medicare patients
purchasing Medigap insurance to provide that coverage. In areas of significant managed care penetration and relatively high
Medicare reimbursement rates, however, MCOs have offered generous pharmacy benefits as a way of attracting new enrollment
into Medicare HMOs. Rising pharmacy costs and declining reimbursement rates have forced many MCOs to drop those
plans entirely or cut pharmacy benefits. Complicating this situation has been legislation in several states mandating the
offering of comprehensive pharmacy benefits for Medicare patients and subsequent court reversal of this legislation in some
of those states. Societys challenge is to balance the obligation to provide optimal treatment for individual patients with
sensible cost considerations. Unfortunately, this often pits the provider against the insurer. The American
College of Rheumatology supports placing treatment decisions in the hands of those providers most knowledgeable about both
the diseases and the newer therapies. The rheumatologist as an expert in both inflammatory and degenerative arthritis is best
qualified to triage and promote the rational use of these treatments. Strict external rules and restrictions imposed
by payors may result in the denial of these agents to those most in need of treatment, leading to increased pain and disability.
Differential rules and regulations on access to these medications can be a subtle way of encouraging chronically ill patients
to switch to other insurers or health plans. There has been a great deal of enthusiasm for disease management
for chronic diseases such as asthma, congestive heart failure and diabetes, as these programs have resulted in rapid cost
containment from decreased hospital and emergency room use. This same enthusiasm should be extended to chronic diseases such
as rheumatoid arthritis, which often requires less hospital care and has a longer and less certain financial payoff.
For those still working, gains can be measured in longer and more productive work lives, and for those no longer in the workforce,
these gains can be measured in improved quality of life. The new medications becoming available for arthritis
must be examined in terms of both their potential additional benefits and greater costs. Potential benefits include increased
effectiveness, a better quality of life, increased work productivity, decreased disability, and possibly a reduction in hospitalization
and joint replacement surgery. Increased costs include considerably higher prices than those for currently existing medications
and any differential cost of toxicity monitoring and the delivery of treatment.
Rheumatologists, the clinicians with the most experience and expertise in diagnosing, evaluating and treating arthritis,
are uniquely qualified to determine the appropriate use of these new therapies, especially the biologic and immunosuppressive
agents. This is particularly true in the case of juvenile rheumatic diseases where small populations make it impractical for
manufacturers to conduct extensive testing. In these cases, clinician experience rather than scientific data becomes the primary
factor in determining clinical pathways. Restrictions requiring the failure of an arbitrary number of other
therapies prior to use of newer agents are inappropriate. Since these new medications have shown promise of being more effective
early in the course of arthritis, the time and expense spent trying serial medications may result in increased joint damage
and disability. Providers and insurers alike need to consider both the effectiveness and cost of medications
when making or paying for treatment choices. This has very significant implications for society as the purchasers of health
care (employers, government and individual patients) decide how best to finance health care in the future
|
|
Factors Involved In Therapy:
Despite promising short-term results for newer DMARDs that have significantly demonstrated effects on functional status
and radiographic progression,there are,at present,insufficient longatudial data to determine whether such a increased expenditure
will eventually be offset by lower costs of the disease. A recent analysis has examined the relative cost effectiveness
of 6 different treatment options for RA patientients in whom MTX therapy has failed:etanercept monotherapy,etanercept plus
MTX,cyclosporine plus MTX,triple therapy with HCQ,SSZ,and MTX,continued MTX monotherapy,and no second-line agent. Triple therapy
was the most cost-effective option,as determined by the ACR 20 improvement criteria or a weighted proportion of patients achieving
ACR 20,ACR 50,and ACR 70 improvement However, as with all cost-effectiveness analyses,there were assumptions
which may limit the applicability of the results. For example,the time horizon for this model was limited to the first 6 months
of therapy. In addition,only a limited number of treatment options were considered in the model. Neither leflunomide nor infliximab
was considered. More data about the impact of newer DMARDs on outcomes such as work capacity and radiographic
progression are needed. In to-days cost-constrained environment,whenever the efficacy and toxicity of treatment
options are equivalent,the lower-cost agent is likely to be used. However,practisioners are increasingly facing situations
in which therapies are no longer equivalent,there is only a partial response to treatment,treatment toxicity or comorbid conditions
contraindicate the use of more traditional agents,or high-risk or severe disease requires the use of newer agents,either alone
or in combination. Providers with sufficient numbers of RA patients in their practise and with longitudinal experence
in treating this disease will,in consultation with their patients,be the best qualified to balance these delicate cost issues
with diagnosis and timely initiation of disease-modifying agents. The goal of treatment is to arrest the disease and to achieve
remission. Although remission occurs infrequently,patients may benefit from nonpharmacologic,pharmacologic,and if necessary,surgical
interventions. Optimal longitudinal treatment requires comprehensive coordinated care and the expertise of a
number of health care providers. Essential components of management include systematic and regular evaluation of disease activity,patient
education/rehabillitation interventions,use of DMARDs,possible use of local or low-dose oral glucocorticoids, minimization
of the impact on the individual's function,assessment of the adequacy of the treatment program,and general health maintenance. In
patients who have unacceptable levels of pain,loss of range of motion,or limitation of function because of structural joint
damage,surgical procedures should be considered. Surgical procedures for Ra include,carpel tunnel release synovectomy
, resection of the metarsal heads,total joint arthroplasty,and joint fusion. New prosthetic materials and cements for
fixing joint prostheses have greatly advanced the prevention of aseptic loosening and have increased the longetivity of total
joint prostheses in patients with RA. Preoperative functional status is an important determinant of the rate
of recovery of functional independence after surgery. strategies for increasing functional recovery include optimization of
preoperative functional status and early surgical intervention. The pre- and postoperative team should include
health care professionals who have performed large numbers of the particular surgical procedures and are experienced in the
care of RA patients.
Depending on the health care setting,the majority of the care of patients with RA may be provided by a single physician
(primary care physician or rheumatologist who also provides primary care ) or the responsibility may be shared. The role of
the primary care physician is to recognize and diagnose RA at its onset and to ensure the patient receives timely treatment
before permanent damage results The rheumatologist should provide support and consultation to the patient and
his or her primary care physician in the diagnosis and treatment of the RA. Since the level of training and experience
in diagnosing and manageing RA varies among primary care physicians,the responsibility for accurate diagnosis and monitoring
of RA activity and/or drug toxicity may appropriately be assigned to a rheumatologist. If the care of the patient is to be
shared,an explicit plan for monitoring RA disease activity and/or drug toxicity needs to be formulated. The patient's preferences
may be the most important factor in decideing which physician(s) assume responsibility for care. A general health
maintenance strategy should be developed,and responsibility for this strategy should be coordinated among the patient's health
care providers. Routine preventive measures,such as screening for hypertension or cancer,should be recommended and risk factors
modified. RA has significant economic implications for the individual patients as well as for society. Individuals
with RA have 3 times the direct medical costs,twice the hospitalization rate,and 10 times the work disability rate of an age
sex-matched population A recent study has shown annual medical costs for a patient with RA to be approximately
$8,500 (U.S.) Annual costs rise as the duration of disease increases and as function,measured by the Health Assessment Questionnaire,declines.
Indirect costs related to disability and work loss have been estimated to be 3 times higher than the direct
costs associated with the disease. Reposibility for the direct medical costs often falls to the third-party payor
and,in part,to the patient,whereas the majority of indirect costs are borne by the government or employers. In a variety of
health care financing systems,the fragmentation of these financial risks and incentives,the frequent turnover of patients
into different risk pools and health care delivery systems,and the relatively slow disease course may all adversely affect
access to appropiate care.
For many years,relatively low-cost options have been available for the treatment of RA. However,the advent of the COX-2
inhibitors,newer DMARDs,including biological agents,and the increasing use of combination therapy have all brought cost considerations
to the forefront. The majority of guidelines have generally avoided cost issues by limiting their scope to an optimum treatment
recommendations. However, ignoring financial considerations would inadequately reflect the impact on daily treatment decisions.
|
|