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Rheumatology

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

FRONTLINE - Based on Sessions from the 64th Annual Meeting of the Canadian Rheumatology Association

Kananaskis, Alberta / February 18-21, 2009

Spondyloarthropathies and Comorbidities: Enhancing Patient Care by Increasing Interspecialty Awareness

Editorial Overview:

Michel Zummer, MD, FRCPC

Head, Division of Rheumatology, Hôpital Maisonneuve-Rosemont, Montreal, Quebec

The spondyloarthropathies (SpAs) refer to a diverse group of inflammatory diseases that include ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, enteropathic arthritis (associated with inflammatory bowel disease [IBD]) and undifferentiated SpA. Since inflammation manifests itself in several organ systems, a variety of specialists are necessarily involved in the treatment of patients with comorbid manifestations of the SpAs, notably rheumatologists, gastroenterologists, dermatologists and ophthalmologists. Cross-specialty communication is essential in helping speed the diagnosis of comorbid conditions and to initiate appropriate treatment in a timely manner.

Prevalence

SpAs are about as prevalent as rheumatoid arthritis, representing approximately 1% of the general population. The SpAs are a diverse group of inflammatory diseases sharing certain predisposing factors and clinical features, the most characteristic of which is sacroiliitis, usually radiographically undetectable until an average of eight years after symptom onset. other common joint symptoms include enthesitis, dactylitis and peripheral arthritis.

AS is the most frequent subtype of SpA, affecting between 0.1 and 0.2% of the us population (Am Fam Physician 2004;69:2853-60) with a higher prevalence in european caucasian males. due to the high prevalence of psoriasis in the general population, PsA is relatively common as well. enteropathic and reactive arthritis, in contrast, are both less frequent.

Diagnosis

Rheumatologists are aware that a patient with arthritis may have extra-articular manifestations, most notably of the eye, the gut and the skin. A thorough patient history can help diagnose and manage comorbidities in a timely manner.

Medical Therapy

As Braun and Sieper pointed out in their review of the biological therapies for SpAs (Rheumatology 2004;43:1072-84), treatment options for patients with more severe forms of spa have been limited in the past when there were no disease-modifying antirheumatic agents. The anti-TNF agents have since become established therapies for SpAs.

Today, three main agents that target tumour necrosis factor-a (TNF-a)—the key pathogenic cytokine involved in all manifestations of SpA—are the monoclonal antibodies infliximab and adalimumab, and the TNF receptor fusion protein etanercept.

The efficacy of each of these anti-TNF agents in the treatment of SpAs is variable and not all are proven to be equally effective for the various extra-articular manifestations.

Review of Key Issues

Uveitis

Although uveitis is most often idiopathic, the high prevalence rate associated with as should alert the ophthalmologist to question the patient about lower back pain and refer accordingly if there is a possibility of AS. Conversely, as several inflammatory eye diseases resemble uveitis, an ophthalmologist can best confirm the diagnosis and initiate proper treatment. Patients with confirmed uveitis may also need to have their treatment modified to better control flares.

Inflammatory Bowel Disease

Treatment of IBD will reduce joint inflammation in many cases. It may be beneficial to have AS confirmed in order to optimize therapy. In SpAs, a confirmation of ulcerative colitis (UC) or Crohn’s disease (CD) will help align therapy. While the evidence is accumulating in favour of biologics to reduce joint progression when administered earlier in the course of the disease in RA and maybe in SpAs, an agent proven to achieve both mucosal healing as well as good control of SpA should be considered first.

Psoriasis and psoriatic arthritis

It may be necessary to distinguish between eczema and psoriasis. A dermatologist should confirm the diagnosis of psoriasis in the patient with SpA. Although an anti-TNF agent may have been prescribed, treatment with supplemental skin therapies may still be required. Patients with psoriasis or PsA who are candidates for anti-TNF agents should be considered for those most effective against symptoms of both diseases.

Summary

Identifying extra-articular manifestations is the first step towards enhancing patient care. Treatment strategies may overlap and decisions between specialists may be required in order to simplify the treatment regimen where possible, to avoid drug-drug interactions, and to optimize response. Once a patient is identified as a candidate for an anti-TNF agent, interspecialty consultation may be helpful in order to ensure the appropriate selection of the anti-TNF agent as well as to optimize management strategies.

Following are more detailed diagnostic and management strategies from specialists treating uveitis, IBD and psoriasis.

Anterior Uveitis and Spondyloarthropathy: Etiology and Treatment

Reviewed by:

Stanley M. Chan, MD, FRCSC

Assistant Professor, Department of Ophthalmology, University of Alberta, Edmonton, Alberta

Uveitis, or intraocular inflammation, is one of the most common extra-articular manifestations of the spondyloarthropathies (SpAs), occurring in 25% to 40% of patients (Rheum Dis Clin North Am 1998;24: 771-84). While approximately half of uveitis cases are idiopathic, of those for which an etiology is known, the most common association is seen with ankylosing spondylitis (AS).

Diagnosis

Uveitis is initially classified anatomically into anterior uveitis (or iritis), intermediate uveitis and posterior uveitis. cardinal signs and symptoms include redness of the eye and pain, light sensitivity and some blurred vision. The pupil may also be small and patients may develop keratic precipitates, although these may not be grossly apparent. Complications include glaucoma, cataract formation, and macular edema. SpA patients tend to develop acute anterior uveitis with or without recurrences.


Other eye diseases, notably herpes simplex keratitis, for which steroid drops can cause worsening, may present with symptoms similar to those of uveitis. That is why referral to an ophthalmologist is essential in order to confirm the diagnosis of uveitis with a slit lamp examination. If a patient cannot see an ophthalmologist immediately, referral to an optometrist may also be helpful.

Given that the most common systemic cause of uveitis is as, ophthalmologists should be familiar with the signs and symptoms of early as. It is most likely to occur in younger caucasian males, usually between 15 and 40 years of age (Am Fam Physician 2004;69:2853-60). There is back pain, inflammatory in nature, which is typically worse late at night and patients often complain of having to get up in the second half of the night because of back pain. on awakening, patients typically experience morning stiffness lasting more than 30 minutes, and their discomfort may be accompanied by alternating buttock pain. Exercise alleviates inflammatory back pain while rest makes it worse. Enthesitis—particularly inflammation at the achilles tendon and plantar fascia calcaneal insertion manifesting as heel pain—is common in AS patients as well. Inflammatory bowel disease is another extra-articular manifestation of as (Arthritis Rheum 2006;54:678-81).

If some of these signs are apparent, a referral to a rheumatologist should be initiated to confirm AS. Treatment may then be initiated to more effectively delay or prevent irreversible joint damage. Introducing an immunosuppressant or an anti-tumour necrosis factor (TNF) agent can prevent uveitis flares and should be administered in consultation with a rheumatologist.

Conversely, in a patient already diagnosed with as, the etiology of the uveitis will be obvious. However, it is important that the ophthalmologist be aware of any potential therapy the rheumatologist has prescribed for symptoms of as, including an anti-tnf agent, as that may modify their own treatment strategy for the uveitis.

Standard Uveitis Treatment

A standard algorithm has been established for the treatment of non-infectious anterior uveitis regardless of its etiology. The treating physician usually begins with steroid drops, typically prednisolone acetate 1%. Cycloplegic drops are also helpful to break down any scarring that may have occurred in the eye. The same drops also dilate the pupil and relax the ciliary muscle that, in spasm, causes sensitivity to bright light.

Of note, approximately 5% of patients who use corticosteroid drops are at risk for elevated intraocular pressure. To offset drop-related glaucoma risk, ophthalmologists may also use glaucoma drops as needed, although not prostaglandin-based glaucoma drops, as they tend to increase inflammation. It is indicated to proceed to periocular steroid injections or, alternatively, oral steroids if the corticosteroid drops are not successful at eliminating the inflammation.

In collaboration with a rheumatologist, the next choice is to proceed to either an anti-TNF agent or an immunosuppressant. When tapering steroid drops, it should be over a period of four to six weeks, as sudden discontinuation can result in a rebound flare-up.

Somewhat paradoxically, some of the treatments that best control uveitis can lead to a number of the same complications as the disease itself. Besides a risk of elevated intraocular pressure, patients can also form cataracts on therapy, while immunosuppression is of concern with both oral prednisone and the immunosuppressants. However, removing a treatment-induced cataract in a quiet eye is much more successful than removing a cataract caused by poorly controlled inflammation in an eye that is actively inflamed.

Reducing Uveitis Flares: The Potential of the Anti-TNFs

There is evidence that anti-TNF agents can decrease the incidence of anterior uveitis in as patients. In one study, Braun et al. (Arthritis Rheum 2005;52:2447-51) undertook a systematic literature review of 397 patients who had received an anti-TNF agent for the treatment of anterior uveitis. of these, 297 had received etanercept and 90 infliximab. The frequency of flare in the placebo group was 15.6 per 100 patient-years vs. a mean of only 6.8 flares per 100 patient-years in the anti-TNF group overall. However, flares occurred less frequently in patients treated with infliximab (3.4 per 100 patient-years) than in those who received etanercept (7.9 per 100 patient-years). While the difference was not statistically significant, it suggested a trend towards increased efficacy for infliximab.

Greater differences between anti-TNF agents were reported in a higher-risk population reviewed retrospectively by Guignard et al. (Ann Rheum Dis 2006;65(12):1631-4). Some 46 patients with spa and at least one uveitis flare received an anti-TNF drug; 33 received one of the two anti-tnf monoclonal antibodies (infliximab or adalimumab) and 13 the soluble anti-TNF receptor etanercept. After a mean of 1.2 years, there were significantly fewer uveitis flares per 100 patient-years among patients receiving an anti-TNF monoclonal antibody agent at 6.8 vs. 58.5 for those receiving the soluble anti-TNF receptor. The authors calculated that they needed to treat two SpA patients with a history of uveitis with infliximab or adalimumab to prevent one flare in one patient over a period of one year.

For reasons that are not yet clear, this would support the literature linking etanercept to inflammatory eye disease where some 17 isolated cases have been reported at last review. These reports suggest that if a patient does develop uveitis while on etanercept, switching to another anti-TNF agent may help ameliorate the inflammation.

Summary

The most frequently occurring extra-spinal involvement in as patients is uveitis, and despite successful treatment, recurrence is common. Ophthalmologists must be familiar with the cardinal signs and symptoms of early as for rheumatology referral if the suspected uveitis etiology is AS. Conversely, in a patient with eye inflammation referred from a rheumatologist, the ophthalmologist can confirm the diagnosis of uveitis and initiate proper treatment. It is, however, important for the ophthalmologist to be aware what treatments the rheumatologist has initiated. While the evidence suggests that anti-tnf agents can decrease the incidence of anterior uveitis in AS patients and appear to favour the anti-TNF monoclonal antibody infliximab, anti-TNF agents and immunosuppressants should generally be introduced in consultation with a rheumatologist.

Inflammatory Bowel Disease and Spondyloarthropathies: Coordinating Optimal Treatment

Reviewed by:

Shane Devlin, MD, FRCPC

Director, Gastroenterology Training Program, Clinical Assistant Professor, Inflammatory Bowel Disease Clinic, Division of Gastroenterology, University of Calgary, Calgary, Alberta

Extra-intestinal manifestations of inflammatory bowel disease (IBD) occur in 21% to 36% of affected patients at some point during their disease history. These patients also experience peripheral and axial arthropathy at a rate of 10% to 35% and AS in 2% to 8% (Figure 1). Articular manifestations are also seen more frequently in association with Crohn’s disease (CD) than with ulcerative colitis (UC) (R
m
1998;24:785-813).

<img3100|center>

Diagnosis

While UC and CD share a similar immunology, UC may be less variable in its presentation. Patients with CD can present with significant variations in disease location and activity, ranging from predominantly colonic disease to pan-intestinal inflammation affecting the colon, small intestine, stomach and duodenum. Symptoms by definition will reflect the location, extent and the severity of the disease. Patients with CD often present with abdominal pain, diarrhea and weight loss, while patients with UC tend to have urgency, tenesmus and bloody diarrhea.

Step-up Treatment in UC

The heterogeneity of CD and, to a lesser extent, UC has important implications in the management of comorbid spondyloarthropathy (SpA). Historically, gastroenterologists followed a “step-wise” approach to the treatment of UC, starting with a 5-ASA compound, then adding a corticosteroid for more severe symptoms, followed by the addition of 6-mercaptopurine (6-MP) or azathioprine (AZA) in the setting of corticosteroid dependence. Infliximab is the only tumour necrosis factor antagonist indicated for moderate to severe UC. In the severe, hospitalized UC patient failing to respond adequately to intravenous corticosteroids, both cyclosporine and infliximab have been demonstrated to be effective, though infliximab is now more commonly used owing to its favourable toxicity profile.

5-ASA is still the mainstay therapy for uc, but there are two distinct populations of patients with UC: those with milder disease who respond well to the 5-ASA compounds and those who have a more aggressive disease course or whose disease course suddenly changes. These latter patients, as well as those who are not responding to 5-ASA, are often treated with corticosteroids and the addition of immunosuppressive agents like 6-MP/AZA. These immunosuppressive agents have a more gradual time of onset; however, if a patient has not responded to a three- to four-month course of adequately weight-based dosing, they are unlikely to respond and consideration should be given at this point to infliximab induction and maintenance.

The natural history of UC also indicates that approximately half of those patients who require corticosteroids for disease control at diagnosis will be either steroid-dependent or will have undergone a colectomy within a year; consequently, if an immunosuppressive agent like 6-MP/AZA is chosen first, assessment of treatment response should again be limited to three to four months. It should also be noted that there is little evidence supporting the use of methotrexate (MTX) in UC, and even the data supporting the efficacy of 6-MP and AZA in UC are not as robust as clinicians would like, giving us further reason to progress relatively quickly to an anti-TNF agent in patients who prove unresponsive or intolerant to traditional medications. Earlier use of infliximab in moderately severe UC patients is preferable to waiting until their disease becomes so active that they require hospitalization as response to medical therapy in this setting is generally lower.

The Anti-TNF Evidence for Treatment of CD

Unlike UC, the efficacy of 5-ASA compounds is questionable in CD and their use should not be advocated, with few exceptions. corticosteroids, 6-MP, AZA and MTX may all be considered first-line agents in CD. MTX use is more common in Canada and Europe than in the US and it is important to recognize that efficacy is felt to be better when using intramuscular (i.m.) or subcutaneous (s.c.) rather than oral administration. In the US, infliximab, adalimumab and certolizumab are indicated for moderate to severe CD, while in Canada and Europe, only infliximab and adalimumab are commercially available at present. The anti-TNF agents are traditionally used in the setting of failure of immunosuppressive agents such as 6-MP/ AZA and MTX. However, there are extensive data to suggest that earlier use, or even first-line use of these agents, may result in better long-term outcomes and improved efficacy. This is an area of intense interest in IBD.

In COMMIT (Combination of Maintenance Methotrexate-Infliximab Trial), investigators compared MTX in combination with infliximab vs. infliximab alone in patients with active CD with disease duration of about 10 years (Feagan et al. Gastroenterology 2008;134:682c). Patients who had initiated corticosteroids within six weeks of study entry were randomized to receive infliximab induction and maintenance alone or in combination with s.c. MTX. Steroids were withdrawn by week 14.

At both week 14 and 50, there were no differences in the percentage of patients in remission and off steroids, with >50% of patients in both groups achieving the primary end point of steroid-free remission. The data for immunogenicity in this trial have not yet been presented but the results suggested no obvious benefit to combination therapy with MTX. In the setting of a patient with a comorbid spondyloarthropathy, the addition of MTX would likely have little utility owing to its lack of efficacy in SpA in general.

Mucosal Healing

Treatment goals for both UC and CD have traditionally been focused around signs and symptoms but these can be unreliable indicators of true inflammatory disease. Increasingly, the new benchmark is achieving mucosal healing (the complete disappearance of mucosal ulceration). Long-term studies have demonstrated that patients with both UC and CD who achieve mucosal healing during the first two to four years of their disease have lower surgical rates, lower hospitalization rates and less need for corticosteroids than those who do not.

Currently, there are good data supporting the ability of infliximab to achieve mucosal healing in both UC and CD. There are less robust data supporting certolizumab for this end point in CD and there is as yet no published mucosal healing data for adalimumab. The key is to choose an agent with the best chance of completely healing the mucosa, thus improving outcomes.

An area of interest in IBD is developing tools to predict severe disease and complications in advance of their occurrence with a view to earlier introduction of effective therapies such as anti-TNF agents. There are a number of clinical predictors which can help in this regard. Various studies indicate that patients with diffuse small bowel disease, those with extensive disease throughout the small and large intestine, those with deep ulcerations, younger patients, those who need corticosteroids from the outset, and those with perianal CD are likely to have a more aggressive disease course. In these patients, a “top-down” strategy—earlier introduction of intensive therapy including anti-TNFs—can be considered. At a minimum, these patients should be treated with more of an accelerated “step-up” approach, placing a finite window of time over which to assess the response to immunosuppressive agents with a plan to then introduce an anti-TNF after three to four months if required.

Conversely, patients whose disease is predicted to take a more indolent course may be treated by the more traditional “step-up” strategy—progressive intensification of treatment after relapses. With either strategy, complete mucosal healing should be an important treatment goal.

Disease-Drug, Drug-Drug Interactions

Although the guidelines advocate the use of anti-TNF agents for moderate to severe CD, not all TNF inhibitors appear equal in terms of benefit in the patient with comorbid SpA. In an important retrospective analysis of nine trials in as, Braun et al. (Arthritis Rheum 2007;57(4):639-47) evaluated the rate of IBD flares in patients who had either co-existing IBD or new-onset IBD during treatment for AS. Analyses showed that the incidence of IBD flares per 100 patient-years was markedly lower with infliximab at 0.2 vs. 2.2 for etanercept and 2.3 for adalimumab. The flare rate among placebo patients was 1.3 (figure 2). both infliximab and adalimumab induce T-cell apoptosis in the gut. However, etanercept only binds soluble TNF, a fact that explains an important aspect of this therapy inasmuch as it has no efficacy in IBD. Therefore, in a pa
SpA, etanercept would not be an ideal choice of anti-TNF therapy.

<img3101|center>

Another important issue that requires careful consideration when selecting treatment for SpA patients with IBD is whether or not they should receive NSAID therapy. Most data are limited to retrospective studies with only a few smaller prospective studies. the preponderence of evidence suggests that COX-2 selective agents are safer in the short term, but no longterm data exist. Moreover, the prospective data are limited to patients with quiescent disease so the risk in patients with more active disease is unknown. Another important factor unaccounted for is the proportion of patients that are taking NSAIDs without the knowledge of their treating physicians. In the setting of quiescent disease, the use of short-term (four weeks) COX-2 selective agents seems to be associated with a risk of relapse of 3% to 5% vs. a 17% to 28% risk with non-selective NSAIDs. However, most patients with IBD have some degree of disease activity despite sometimes minimal symptoms and in this setting, the use of NSAIDs should be seen to be contraindicated.

In patients with a comorbid SpA for which NSAID therapy is otherwise a mainstay, the persistence of mucosal inflammation in the setting of their use would be a good indication for an anti-TNF agent to treat both diseases, especially given the lack of efficacy of immuosuppressive agents like MTX in SpA.

Potential drug-drug interactions in the management of the SpA/IBD patient are not of great concern and some are actually beneficial. For example, MTX delays the clearance of infliximab from the circulation, thereby prolonging patient exposure to the drug. MTX also increases initial adalimumab drug concentrations; co-administration of 6-MP or AZA with allopurinol does, however, increase the risk of leucopenia, as may co-administration of mesalamine with 6-MP or AZA.

Collaboration Between Specialists

In referring patients with symptoms of IBD, it would be helpful to have a good description of the patient’s GI symptoms, including the presence of bloody stool, nocturnal symptoms, evidence of weight loss, a family history of IBD, as well as any laboratory results that could help confirm the diagnosis, particularly CBC, ESR, CRP and albumin.

A treatment plan for symptoms of articular involvement is necessary and an anti-TNF agent may be considered. Keeping in mind that our prime treatment goal in the management of the IBD patient is mucosal healing, gastroenterologists will likely choose an agent which has been proven to be most effective at inducing mucosal healing. The anti-TNF agents are clearly effective in the management of joint pain as well.

Patients with concomitant SpA referred to a gastroenterologist should also be aware they will very likely undergo endoscopic investigation, as up to 68% of SpA patients will have subclinical IBD that is largely asymptomatic (J Rheumatol 1995;22(12):2273-8).

Summary

Even in the absence of any extra-intestinal manifestations, UC and CD can be difficult to manage. Given that infliximab can be considered as a first-line agent in moderate UC, and that the monoclonal anti- TNF agents are indicated in the CD patient, infliximab in UC and infliximab or adalimumab in CD should be considered when conventional therapy fails to control either the musculoskeletal, cutaneous or ocular manifestations of IBD.

Spondyloarthropathy, Psoriasis and Psoriatic Arthritis

Reviewed by:

Richard Langley, MD, FRCPC

Associate Professor/Director of Research, Division of Dermatology, Dalhousie University, Halifax, Nova Scotia

Between 60% and 70% of psoriasis cases precede psoriatic arthritis (PsA); about 10% to 15% can occur simultaneously and in about 10% to 15% of patients, PsA presents first. Thus, the majority of patients with PsA will have manifestations of inflammation in the skin first and then go on to develop arthritis at a later stage. Once thought to occur in only about 5% of patients with psoriasis, it is now recognized that PsA occurs in upwards of 30% to 40% of patients with psoriatic skin lesions.

Diagnosis

A clinical diagnosis of psoriaisis is a key factor in the recent Classification Criteria for Psoriatic Arthritis (CASPAR) for diagnosis. There are certain clinical features that are helpful to distinguish between papulosquamous disease—psoriasis being the most common—and eczema. Psoriatic lesions have well defined borders and they are red and scaly. They also have a certain pattern of localization, typically occurring on the scalp, the elbows, the knees, behind the ears as well as in the axilla, the groin and the interglutteal cleft. It is also important to examine the nails as lesions, including pitting and onycholysis, occur in over 80% of patients with PsA.

Medical Therapy

If the lesions are localized, dermatologists will typically use topical agents first but treatment should be tailored to the site involved. If, for example, lesions are on the face, a low-potency steroid like hydrocortisone 1% cream or a topical calcineurin inhibitor is reasonable. Lesions on the scalp are best treated with a lotion that patients can rub directly onto their scalp. Alternatively, calcipotriene is a vitamin D cream that can work well and is not associated with long-standing effects of the steroids on the skin.

High-potency steroids such as clobetasol may also be used, ideally in an ointment form, as the ointment is more potent than the cream and patients can cover up the treatment at night if the lesions are on the shins or the elbows. However, high-potency steroids should only be used for restricted periods, otherwise they may cause local adverse events (i.e. atrophy of the skin).

More widespread or disabling psoriasis requires a systemic approach. Psoriasis that does not respond to topical treatments within a reasonable time frame (approximately four months) should also be treated systemically. Phototherapy is typically offered first, but other systemic agents (methotrexate, retinoids, cyclosporine) or biologic agents can be considered. there are multiple points in the psoriatic cascade at which tnf plays a pivotal role.

The first reported TNF antagonist in psoriasis was by Chaudhari et al. (Lancet 2001;357:1842-7) where investigators found that 82% of psoriasis patients who received infliximab 5 mg/kg had a 75% improvement in their Psoriasis area and severity index (PASI) score at week 10. Previous studies using t-cell agents in psoriasis showed that only about 20% of patients achieved a similar PASI score, an observation that has contributed to the infrequent use of the t-cell agents in primary psoriasis. Since the t-cell agents are not effective in PSA, they are not indicated in this setting either.

A meta-analysis of six randomized controlled trials involving 982 PsA patients confirmed that all three anti- TNF agents—infliximab, adalimumab and etanercept— were significantly more effective than placebo at eliciting a response in both the skin and the joints, with no significant differences being demonstrated between the three agents (Nat Clin Pract Rheumatol 2008;4(10):510- 1). Thus, from a perspective of controlling joint disease in PsA, all three agents may be considered equal.

However, according to the group for research and assesment of Psoriasis and Psoriatic arthritis (GRAPPA), infliximab has a preferential role in the treatment of dactylitis and nail psoriasis, and is currently the only anti-TNF agent for which evidence supports its use alone.

Evidence and Consideration for Anti-TNF Therapy

according to the british association of dermatology, patients with severe disabling psoriasis who meet all of the following criteria should be considered for biologic therapy:

• Body surface area (BSA) involvement of greater than 10% and/or significant involvement of the face, hands, feet or genital region.

• Failure to respond to, contraindicat
t of methotrexate and cyclosporine.

• Failure to respond to, intolerant to or unable to access phototherapy.

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There have been a number of studies evaluating the various anti-TNF agents in the treatment of psoriasis and all show some efficacy. However, there appear to be differences in the magnitude and rapidity of response depending on the agent used.

In a study presented by Sterry et al. at the 13th Congress of the European Academy of Dermatology and Venereology (EADV) in 2004, patients received etanercept either 25 mg twice weekly or 50 mg twice weekly for 24 weeks. At week 12, according to severity of disease, 34% to 49% of patients had achieved a PASI-75 response, which rose to 50% to 60% by week 24. At EADV 2005, PASI-75 responses to adalimumab in psoriasis patients were presented. Results showed that 53% to 80% of patients who received every-other week or weekly adalimumab achieved a PASI-75 at week 12 and by week 60, those percentages remained stable at 58% and 64%, respectively.

Our per-protocol analysis of another group of psoriasis patients treated with infliximab showed that at week 10, approximately 80% of patients had achieved a PASI-75, with slightly over 70% maintaining this response by week 50 (figure 1).

Since there are differences in the magnitude and rapidity of response between the anti-TNF agents as they affect the skin, these differences should be discussed with PsA patients who are candidates for anti-TNF therapy.

Adverse Events

In the same meta-analysis comparing the three anti-TNF agents in PsA, there were no significant differences between any of the TNF inhibitors and placebo in the proportion of patients experiencing withdrawal for any reason or withdrawal due to adverse events (AEs), serious AEs or upper respiratory tract infections. Importantly, there is still a need to assess the long-term risk of using these drugs in the management of PsA even though evidence to date indicates they are safe and effective in the short term.

Co-Management Between Specialists

Referral to a dermatologist is reasonable if there is uncertainty about the diagnosis; if the patient has more severe disease, i.e. >10% BSA affected; if the disease is having a negative impact on the patient’s quality of life; if patients with milder disease are not responding to treatment; or if patients are unsatisfied with their treatment. Other candidates for referral include patients with lesions which are either TNF-induced or pustular.

Summary

Psoriasis can significantly impair quality of life for those with moderate to severe disease. Effective topical treatments should be tailored to the lesion site when indicated. In more widespread or disabling skin lesions or when there is comorbid joint involvement, the rationale is to use an anti-TNF agent as TNF is intimately involved in both joint and skin manifestations of inflammation. While the anti-TNF agents have all been shown to be effective in PsA, they do differ in terms of the magnitude and rapidity of response in primary psoriasis, and these differences may be relevant when deciding upon a treatment plan.

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