Psoriatic Arthritis Clinic [Drug information] [PSA Publications]
(Newsletter No. 10 May 2007)

History of the Psoriatic Arthritis Clinic
What is Psoriatic Arthritis?
Why is the Psoriatic Arthritis Clinic Special?
What have we learned from these assessment of patients in the Psoriatic Arthritis Clinic?
Are there new therapies available for patients with Psoriatic Arthritis?
Are we any further ahead in the understanding of the cause of Psoriatic Arthritis?
Are hereditary factors important in Psoriatic Arthritis?
Summary

History of the Psoriatic Arthritis Clinic [Top]

      The Psoriatic Arthritis Clinic has been at The Centre for Prognosis Studies in the Rheumatic Diseases since October 1995. With the exception of 2 years of renovation,the Centre has provided a very comfortable environment for our patients, with a large waiting area, which is in close proximity to the coffee shop, the laboratory for routine blood tests is within the facility, and the x-ray department is just down the corridor. With the opening of the Leonard Street entrance in 2007, it has become much easier to approach the Centre.

      The Centre provides an improved research facility for our studies. The physicians working at the Centre are now in close proximity to the "laboratory" which includes research assistants, biostatisticians and programmers, as well as the computer equipment. This has further facilitated and enhanced our research endeavours, helping us to get closer to understanding the disease and develop a cure. In addition, we now have a clinical trials area as part of our Centre.

      The purpose of this Newsletter is to update our patients on advances in research and treatment for patients with Psoriatic Arthritis. Since there are always new patients entering the Clinic we provide some basic information about the disease.

 

What is Psoriatic Arthritis?[Top]

      Psoriatic Arthritis is an inflammatory arthritis associated with psoriasis. The arthritis presents with pain, swelling and stiffness in the affected joints and occasionally with reddish/purplish discoloration over these joints. It may also affect the neck and the back, causing pain, stiffness and limitation of movement. Psoriasis is a common skin disease, which affects 1-3% of the population. Psoriatic Arthritis may develop in as many as one third of the patients with psoriasis; thus Psoriatic Arthritis is a relatively common condition. Psoriatic Arthritis was considered a mild form of arthritis and physicians have tended not to treat it very aggressively. The cause of the disease and the reason for its persistence are not well understood.

 

Why is the Psoriatic Arthritis Clinic special?[Top]

      The University of Toronto Psoriatic Arthritis Clinic was started in 1978 by Dr. Dafna Gladman. It was developed because there was little information about this condition. As noted in the following sections, we have learned a great deal since its inception. The Clinic generally takes place on Monday morning between 9 a.m. and 12:30 p.m., and Wednesday afternoons, between 1:00 and 5:00 p.m. Patients are initially evaluated by a rheumatology trainee who is particularly interested in this disease. All patients are then reviewed by Dr. Gladman, both in order to provide the specialized care, and to assure that the information that is collected is accurate. The patients are therefore evaluated in a standard way, according to a specially designed format, which includes a complete history, physical examination, blood and urine tests and x-rays at regular intervals. This information is entered into a computer database. In this way, different patients can be compared, and knowledge about the disease is enhanced. The Clinic includes over 1000 patients who have been followed longitudinally. This Clinic constitutes the largest and the most comprehensively studied group of Psoriatic Arthritis patients in the world. Various centres around the world have invited Dr. Gladman to speak and share what we have learned about this disease. Similar clinics are now being establihed around the world.

 
 

What have we learned from these assessments of patients in the Psoriatic Arthritis Clinic?
[Top]

      A great deal of knowledge has been gained at the Psoriatic Arthritis Clinic. The recognition that the disease may result in a destructive form of arthritis in about one fifth of the patients has changed the approach of rheumatologists all over the world towards the disease. This information could not have been gathered in any other way. The availability of the computer database allows us to study the patterns of the disease and its progression, which cannot be identified when a physician looks after a small number of patients in his/her own office and does not have the information readily at hand. We have confirmed that the methods we use to assess patients clinically, in terms of active inflammation and joint deformities, as well as the interpretation of the x-ray changes, are reliable. This allows us to continue with our studies of prognosis. Indeed, since we published the results of our initial study in 1987 several other centres in the world have become interested in the study of Psoriatic Arthritis, and are using our definitions and methods in their patient populations. Confirmation of our findings is now being published by various investigators. Most recently we have the methods used in our Clinic are also reproducible by physicians from different centres around the world. The assessment of joint tenderness, sausage digits, and spinal disease have been proven reliable in two international studies carried out in our Centre - the INSPIRE study and the GRAPPA IMPART study.

      In addition to joint inflammation and the development of joint deformity and damage, we have realized that the patients’ perception of their health status and quality of life is an important outcome measure. Our patients have helped us evaluate the quality of life in Psoriatic Arthritis. We found that these measures are important factors in the overall assessment of patients with Psoriatic Arthritis, as they provide additional information about the patients that is not reflected in our measures of clinical activity and damage. We have now incorporated these measures into our regular assessments. When we evaluate the results of new therapies, we want to assure that we assess their effect on patients’ quality of life and not only the traditional clinical measures. We have found that while patients with Psoriatic Arthritis report a reduced quality of life than otherwise healthy individuals, they fare better than patients with Systemic Lupus Erythematosus and scleroderma. Patients with Psoriatic Arthritis also complain of fatigue that is in part related to the degree of joint inflammation they have. We recently validated a new fatigue scale which will be included in clinical trials.

      A major investigation into the prognostic factors of this disease has been carried out over the past few years, a project supported initially by the Ontario Ministry of Health and more recently by the Medical Research Council of Canada and the Canadian Institute for Health Research(CIHR), and more recently by the Krembil Foundation. The results of this investigation have taught us that joint inflammation predicts progression of both clinical and radiological damage. This suggests that we need to be more aggressive with our therapy earlier in the course of this disease. This is particularly important since we have also found that patients with Psoriatic Arthritis have an increased death rate compared to the general population. While the causes of death among patients with Psoriatic Arthritis are similar to those of the general population, an important risk factor for death among patients with Psoriatic Arthritis is disease severity at presentation. It therefore appears that if we treat our patients earlier we may prevent some of these problems. More recently we documented that in addition to the information collected at first visit, the degree of joint inflammation at each visit is predictive of subsequent damage. Thus, patients with Psoriatic Arthritis should be followed with careful documentation of joint inflammation so that appropriate intervention is provided in a timely manner. We have also identified a group of patients who have a better course, and actually achieve clinical remission. We defined remission as absence of clinical evidence of inflammation for at least a year. Seventeen percent of our patients achieved clinical remission, but only a few achieved what we call complete remission. These patients had no evidence of inflammation or damage and were not taking any medications. Moreover, half of the patients who achieved clinical remission went on to flare after a period of about two and a half years. Male gender and a low number of actively inflamed joints at presentation were associated with remission. This information confirms that we must continue to be vigilant in our follow-up of our patients with Psoriatic Arthritis and we treat them appropriately along the course of their disease.

      We have found that there are certain genetic markers present on the membranes of white blood cells, also serve as indicators of progression, and these may be more important than the clinical features, which may change with time. These markers are known as HLA antigens. Many people may recognize this term in conjunction with organ transplantation. Although HLA antigens were initially identified in the context of transplantation, it soon became clear that they were important in the immune response, the ability of our bodies to fight off infections. Certain of these markers are more likely to occur among patients with Psoriasis and Psoriatic Arthritis than in the general population, and thus are thought to play a role in the development of the disease. Through collaborations with colleages in Newfoundland and the National Institutes of Health we have also identified other genes which predispose to the development of Psoriatic Arthritis. We are continuing these investigations to try and identify the exact markers and identify the gene(s) responsible for disease severity. This information is crucial, since these markers may identify those individuals destined to develop a more severe form of arthritis and provide for a more rational approach to the treatment of individual patients. Fortunately we are recently successful in obtaining a large grant from the CIHR for an international study to address these genetic factors and compare patients with psoriatic arthritis to patients with uncomplicated psoriasis.

 
 

Are there new therapies available for patients with Psoriatic Arthritis?[Top]

      A number of medications have been tested in our Psoriatic Arthritis Clinic. These include the retinoic acid analogue, Tegison; an anti-inflammatory drug called Meclomen, Gold therapy, Methotrexate therapy, Sulfasalazine (Salazopyrine) therapy, Imuran therapy and Fish Oil. While these medications may work for some of our patients, they do not work for all patients, and for the most part these medications do not prevent progression of joint damage. The turn of the millenium has brought with it new hope for people suffering from Psoriatic Arthritis. Several new medications which were originally developed for Rheumatoid Arthritis, including Leflunomide (ARAVA®) and several anti-TNF agents, have now been tested for efficacy in Psoriatic Arthritis. We participated in several of these studies, including the leflounomide, Infliximab and adalimumab trials. While Leflunomide was found to work in about 40% of the patients, the anti-TNF agents show a response in 60-70% of the patients. They work for both skin and joint manifestations, and they seem to prevent progression of radiological damage. No Canadian centres were included in the trials of etanercept (ENBREL) in Psoriatic Arthritis. We reported our own experience with the use of Etanercept in our Clinic. As demonstrated in two randomized controlled trials, this anti-TNF agent has demonstrated its effectiveness in the Clinic setting, and is generally well tolerated.

      Thus there are three anti-TNF agents which are effective for both skin and joint manifestations of Psoriatic Arthritis, and which are approved in Canada. The difficulty is that the drugs are expensive, and physicians are required to use other medications such as methotrexate and leflunomide or sulfasalazine before prescribing these newer medications to patients with Psoriatic Arthritis.

      Another biologic agent, efalizumab, which has worked for psoriasis was recently tested in Psoriatic Arthritis. It did not show a response in Psoriatic Arthritis. Another agent, alefacept, which has already been approved for the treatment of psoriasis was tested in Psoriatic Arthritis and proved to be efficacious in addition to methotrexate. However, its effect is not quite as marked as that of the anti-TNF agents. These drugs are not approved for Psoriatic Arthritis in Canada.

      There are several other medications which are currently under investigation or will be tested in Psoriatic Arthritis. This is an exciting time for patients with Psoriatic Arthritis and the physicians looking after them. There are now several approaches to treat the disease. It is most important that the diagnosis be made early and appropriate therapy is offered as soon as the diagnosis is made.

 

Are we any further ahead in the understanding of the cause of Psoriatic Arthritis?[Top]

      There has been evidence to support a role for immunological foctors in the development of Psoriatic Arthritis. We and others have found some abnormalities in the immune function (defense mechanisms) in patients with both Psoriasis and Psoriatic Arthritis. We have also identified several patients whose psoriasis and arthritis were precipitated by injury, suggesting that this may be a factor in the development of the disease. Further studies into the role of trauma are currently on the way.

Are hereditary factors important in Psoriatic Arthritis?[Top]

      We know that about 40% of patients with Psoriatic Arthritis have relatives with either Psoriasis or Psoriatic Arthritis suggesting some hereditary contribution to the development of these conditions. The discovery of the HLA genes on chromosome 6 has facilitated genetic studies in this disease. These genes have a role in the susceptibility to certain diseases, as well as in the immunologic response. Our studies and those of other investigators have shown that there is an association between Psoriasis and Psoriatic Arthritis and certain HLA markers, and that there are certain antigens that identify those patients with Psoriasis more likely to develop Psoriatic Arthritis. As mentioned earlier, certain HLA markers have actually been found to predict progression of Psoriatic Arthritis and some have been associated with particular disease manifestations. There are now new techniques to identify these genes and their variability in more detail. We have already reported that the HLA-C locus marker associated with Psoriatic Arthritis is more easily detected with the new molecular techniques and is associated with an earlier age of onset of Psoriasis. Moreover, several new genes have recently been identified which may be relevant in Psoriatic Arthritis.

      We are currently looking for the role of other genes as well. In collaborations with colleagues in Newfoundland we have begun family studies, to try and identify the genes(s) responsible for the disease, which we believe to be on the short arm of chromosome 6, where the HLA region is. This investigation involves an accurate evaluation of the family members affected with either Psoriasis or Psoriatic Arthritis, which at present requires a complete assessment of all relatives in our Centres. We are currently working on a screening questionnaire, which if validated will allow us to determine disease status in relatives without the need to assess all of them. With the help of donations from some of our patients we have been able to fund fellows specifically to train in our Clinic and help carry out this research. We hope the patients and their families will continue to support our efforts, which are partially funded by the Canadian Institute of Health Research (CIHR) and The Arthritis Society.

      The University of Toronto Psoriatic Arthritis Program is unique in that in addition to the Psoriatic Arthritis Program we also have an HLA laboratory, directed by Dr. Gladman. This laboratory originated at the Wellesley Hospital in 1978 and moved to the Toronto Hospital Regional HLA Laboratory in 1995. The investigations noted above were carried out in these laboratories. In 1999, the laboratory moved to the Toronto Western Hospital, facilitating this research. A generous donation enabled the laboratory to be a fully functional independent molecular lab. Genetic studies can now be carried out with DNA isolation, HLA typing by molecular techniques, storage of DNA for genome scans, and data analysis. This laboratory supports both our local efforts, as well as the family studies carried out in Newfoundland. The laboratory research program has also been supported by The Arthritis Society, The Medical Research Council, and the CIHR.

      Dr. Gladman was recently elected President of the Group of Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). This is an international group of rheumatologists, dermatologists, radiologists, methodologists and others interested participants who have gathered to study psoriasis and psoriatic arthritis with the goal of improving outcome for patients with these conditions. The group is involved in research and education. Through this group new classification criteria for psoriatic arthritis were recently published, domains to be included in clinical trials and observational cohort studies in psoriatic arthritis were identified, and reliability studies, genetic studies, and studies into tissue histology in both psoriasis and psoriatic arthritis have been carried out.

 

Summary[Top]

      In summary, we have learned a great deal about the disease process in Psoriatic Arthritis in the past few years. We now know that the disease may be more serious than previously suspected, at least in certain patients. We appreciate that if we are going to make a difference we need to diagnose and treat patients early. We now have an idea about the type of patient who needs to be treated more aggressively. We are currently developing an approach based on the recently identified markers for disease progression in Psoriatic Arthritis. We believe that by studying the disease in detail we will be able to find the cause and then the cure for Psoriatic Arthritis.