Assistant Director of Pharmacy, Clinical Services
Royal Liverpool and Broadgreen University Hospitals NHS Trust
Liverpool John Moores University School of Pharmacy and Chemistry
These are exciting times for those working in the field of rheumatology. New and innovative treatments are beginning to increase in number and complexity, and the future for the effective treatment of rheumatoid arthritis (RA) looks increasingly promising. The importance of drug therapies in inducing and maintaining remission of the disease means that pharmaceutical care has a key role in ensuring patients gain the maximum benefit and minimum harm from their medicines. This article comments on key areas of the drug treatment of RA and on the opportunities for and responsibilities of pharmacists involved in this area.
Developments in analgesia
Among the symptoms described most commonly by RA patients, pain and inflammation are traditionally managed with the use of nonsteroidal anti-inflammatory drugs (NSAIDs); however, the use of these drugs has been associated with concerns about gastrointestinal safety. To some extent, these concerns have been altered, with the more recent launch of cyclo-oxygenase (COX) 2 inhibitors. While the trials suggest these drugs are safer than their nonselective counterparts, a number of questions about their safety still remain. Since the UK National Institute for Clinical Excellence (NICE) guidance was published there have been a number of different interpretations of its findings, and further research is required to definitively establish the risks and benefits of COX-2 inhibition over traditional NSAIDs.(1) For some, the issue is further clouded by unresolved questions regarding cardiovascular disease and the coprescription of low-dose aspirin and proton pump inhibitors. Protecting patients from the possible effects of inappropriate NSAID use is a key role for pharmacists, and it will be difficult to produce some definitive answers with the evidence currently available. Nevertheless, managing pain and inflammation remains a key area of patient concern, and it is important that steps are taken to ensure patients have as great a quality of life as possible.
Developments in disease-modifying drugs
It is now common for patients with newly diagnosed RA to be initiated with disease-modifying antirheumatic drug (DMARD) therapy early on in the course of their disease. For many, this is the first step in a management strategy involving increasing or decreasing doses, experiencing side-effects, and transferring to other or additional DMARDs. For some, it will mean taking medicines to counteract or reduce the side-effects of other therapies and many years of close monitoring of their biochemical and haematological parameters. While many patients may be used to less noxious drugs such as simple analgesics, the concept of taking potentially toxic medicines may be extremely worrying. For these reasons, the importance of appropriate counselling by the rheumatology team is hugely important.
The use of DMARDs in rheumatology has become simpler with regard to monotherapy, with most centres using methotrexate or sulfasalazine as first choice. The addition of leflunomide to the DMARD group now means that for the first time in a number of years another effective option exists. There remains a significant amount of debate, however, about what to do next. Although it has become more common to see patients on combinations of DMARDs, early studies suggested that these did not help patients. More recent studies have shown more promise(2,3); however, it has been questioned whether these combinations improve outcomes in the longer term.(4)
Another growing area of interest is the use of sub-cutaneous methotrexate. Although methotrexate is considered by many to be the gold standard DMARD for RA, treatment is often withdrawn due to poor tolerance rather than lack of efficacy, and an increasing number of patients are being treated with subcutaneous methotrexate to avoid the gastrointestinal side-effects commonly associated with the drug. The subcutaneous route is also considered to address any queries over absorption that may have resulted in poor efficacy. It has very recently been advocated that this approach should be used before patients are considered for biological therapies.(5) Again, the issue of patients self-administering potentially toxic medicines is an important area for the pharmacist to consider in terms of patient counselling and safe disposal of excess drug and injection paraphernalia.
Antitumour necrosis factor drugs and anakinra
Infliximab and etanercept have been available for almost three years now, and in that time there have been a number of safety concerns. The incidence of neoplastic disease and general infection has not been quite as prominent as first feared, but new concerns about tuberculosis, congestive cardiac failure and demyelinating disorders have since arisen. However, we are still in the early days of using these drugs, and it will be interesting to see what we are finding in patients in 10–15 years time.
Further trials will no doubt come to the fore, and it would be useful to compare these agents with subcutaneous methotrexate or aggressive multi-DMARD therapy rather than methotrexate alone. Evidence to support their use, in terms of patients requiring less physiotherapy, fewer hospital admissions and increasing the number of patients returning to work, would help their cause in obtaining funding. The launch of adalimumab this autumn will see the third of the antitumour necrosis factor drugs available in the UK. Some, given the rapidly increasing number of publications concerning their use, already consider NICE guidance for the anti-TNF drugs to be out of date.(6) Anakinra does not appear to have made as great an impact as infliximab and etanercept and will be the subject of final guidance from NICE in January 2004.(7) Given the costs and potential problems these medicines create, a role for pharmacists in monitoring NICE guidance implementation, and monitoring for adverse effects and outcomes of therapy is clearly important.
Other pathologies and patient-specific characteristics
While it is imperative to focus on patients’ immediate medical needs, it is also important to look at their other medical problems to ensure effective management. These medical problems may have a significant impact on the medicines used to treat RA: for example, hypertension or congestive cardiac failure may be worsened by NSAIDs, age and other factors may increase the risk of gastric ulceration with the use of NSAIDs, pregnancy has an important bearing on the use of DMARDs, and significant congestive cardiac failure may preclude the use of the biologicals. Given the use of corticosteroids in RA, preventing adverse effects such as osteoporosis is also a key role.
While it is well known that many patients with RA may have problems opening the packaging of their medicines, it is somewhat alarming to find that a large proportion of these patients are never offered advice or assistance with this aspect of their treatment. A number of patients have their own ways of dealing with this, such as using a scalpel to cut open foil in blister packaging, but others face a daily struggle to open their medicines containers.
Patients with RA often use eye drops to relieve dry eyes, and some products are more suitable, and possibly more effective than others. Inhalers are also problematical, and it is a shame that providing patients with one inhaler device for the two or three different medicines they may have to inhale is prevented for reasons that only the pharmaceutical industry can explain.
Clinics and prescribing
Although there is not a great deal of published work to support the role of pharmacists in clinics, training in supplementary and independent prescribing and the use of trust administration and prescribing protocols mean that pharmacists have an increasing opportunity to work with the rest of the rheumatology team. There are various models of pharmacist-led clinic, and given the drug-focused treatment of RA an opportunity exists for pharmacists to see patients they may not have done on an inpatient basis.
Issues around anti-TNF drugs apart, the delivery of pharmaceutical care to patients follows a similar path to that which it might have done 20 years ago – if we had been practising it then! Patients should be monitored for pain, inflammatory markers, prevention of NSAID-related complications, side-effects of steroids, monitoring of DMARD therapy and suitability and response to anti-TNF therapy.
As with all specialties, patients’ concurrent medical conditions and beliefs must also be borne in mind, and this is a key aspect of the pharmacists’ role with their generalist background. With the development of new classes of medicines and the increasingly complex mix of medicines and evidence, the future of pharmaceutical care in rheumatology faces some interesting challenges.
- Available from URL: http://www.nice.org.uk/pdf/coxiifullguidance.pdf
- Kremer JM, Genovese MC, Cannon MD, et al. Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. Ann Intern Med 2002;137:726-33.
- Mottonen R, Hannonen P, Leirisalo-Repo M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. Lancet 1999;353:1568-73.
- Maillefert JF, Combe B, Gouopille P, et al. Long term structural effects of combination therapy in patients with early rheumatoid arthritis: five year follow up of a prospective double blind controlled study. Ann Rheum Dis 2003;62:764-6.
- Bingham SJ, Buch MH, Lindsay S, et al. Parenteral therapy should be given before biological therapy. Rheumatology 2003;42:1009-10.
- Available from URL: http://www.nice.org.uk/pdf/RA-PDF.pdf
- Available from URL: http://www.nice.org.uk/Docref.asp?d=79012.