Michael D. Lockshin, MD

Ask the Expert Decision-making in such young women can be difficult and among the most agonizing - for both patient and physician. It usually requires a very prolonged conversation with the patient and her immediate family, whether parents or significant other. While such women clearly need treatment - and preservation of fertility is obviously desired - it is very difficult to know the best option. We use one of three options in these circumstances:

1. administer full-dose cyclophosphamide (with prednisone) and hope for the best; 2. administer prednisone and mycophenolate, although there is a little controversy as to whether this is as effective as cyclophosphamide; or 3. pretreat the patient with leuprolide acetate (Lupron) and administer prednisone and cyclophosphamide, although it makes young women pretty miserable and it must be continued for the full duration of treatment.

None of these options is ideal. The usual solution is number 2. Low-dose cyclophosphamide would not be helpful. The Europeans (English and French, in separate investigations) have published on "low-dose" cyclophosphamide in uncontrolled trials, but their definition of low-dose is 0.5 g per meter squared every two weeks, rather than the NIH protocol of 1.0 g per meter squared every month - so I don't get the point of it all. It seems to me the total cyclophosphamide dose is more or less the same, and they have provided no additional data regarding fertility or other critical information. See the complete article on the Hospital for Special Surgery's web site

Ask the Expert
Michael D. Lockshin

Several aspects of psoriatic arthritis make it hard to answer questions about its treatment succinctly.

First, there are at least three forms of psoriatic arthritis: in some patients it looks very much like rheumatoid arthritis, in others like ankylosing spondylitis, and in still others only the end joints of the fingers (and, usually, the fingernails) are involved. What may work for one type of psoriatic arthritis may not for another.

Second, although most doctors think all inflammatory rheumatic diseases are autoimmune, it has been very hard to identify specific problems with the immune system in patients with psoriasis or psoriatic arthritis. Since most treatments for autoimmune disease change the function of specific parts of the immune system, it is hard to know which function to identify as a potential target when you are not even certain that the immune system has gone awry.

Third, compared to rheumatoid arthritis, psoriatic arthritis is fairly uncommon. It is an ‘orphan’ disease, and most treatments that are tried have been borrowed from another disease rather than specifically developed for psoriatic arthritis.

That said, much has happened in the last few years. For at least the past two decades, the standard treatment for psoriatic arthritis has included nonsteroidal anti-inflammatory drugs, sulfasalazine and, in more severe cases, methotrexate or cyclosporin. Corticosteroid drugs such as prednisone have not been very effective. Methotrexate, the most effective, has the added advantage that it treats the skin condition as well as the joints, but even with it many patients failed to respond well. Drugs useful in treating the skin disease, such as acitretin (Soriatane), sometimes work in refractory cases but are often toxic.

About 5 years ago the dramatic success in rheumatoid arthritis of the new class of drugs called biologics, specifically inhibitors of a small chemical called tumor necrosis factor alpha led to trials of these drugs in psoriatic arthritis. In brief, TNF alpha inhibitors — etanercept (Enbrel) and infliximab (Remicade) - work extremely well in many patients with psoriatic arthritis of all three types[1],[2],[3]. Adalimumab (Humira) is a very recently released similar drug that may be expected to work as well. These drugs may work by inhibiting TNF alpha or by breaking the inflammatory cycle in a different way. TNF alpha inhibitors also appear to protect bone from being eaten away[4]. In clinical trials, these drugs reduce inflammation and prevent deterioration over several years, and they improve skin disease as well.

As a result of success with TNF alpha inhibitors, other biologics, which have different effects on the immune system, are now under trial[5],[6],[7]. The down side is that all of these drugs are extremely expensive, that they are injectable rather than available in pill form, and that their major side effect is that they make recipients susceptible to certain kinds of infections. Otherwise they are not particularly difficult to take. Specific information about these drugs can be found elsewhere on this website.

The details of how these biologics affect the immune system is less important than the fact that they do work in psoriatic arthritis. In doing so, they teach us that the immune system is abnormal in psoriatic arthritis, that very specific abnormalities can be corrected, and that the development of treatments based on an immunological theory of this disease is valid. Thus, in the next several years, we can expect to see many more immunologically active drugs - largely biologics - developed for and tried in psoriatic arthritis. With luck, one or more of the new drugs will be inexpensive, orally administered, side-effect free, and possibly even curative.

See the complete article on the Hospital for Special Surgery’s web site
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[1] Braun J, Sieper J. Role of novel biological therapies in psoriatic arthritis : effects on joints and skin. BioDrugs. 2003;17(3):187-99.

[2] Anandarajah AP, Ritchlin CT. Etanercept in psoriatic arthritis. Expert Opin Biol Ther. 2003 Feb;3(1):169-77.

[3] Yazici Y, Erkan D, Lockshin MD. Etanercept in the treatment of severe, resistant psoriatic arthritis: continued efficacy and changing patterns of use after two years.Clin Exp Rheumatol. 2002 Jan-Feb;20(1):115.

[4] Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM. J Clin Invest 2003 Mar;111(6):821-31. Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest. 2003 Mar;111(6):821-31.

[5] Kraan MC, van Kuijk AW, Dinant HJ, Goedkoop AY, Smeets TJ, de Rie MA, Dijkmans BA, Vaishnaw AK, Bos JD, Tak PP. Alefacept treatment in psoriatic arthritis: reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis. Arthritis Rheum. 2002 Oct;46(10):2776-84.

[6] Utset TO, Auger JA, Peace D, Zivin RA, Xu D, Jolliffe L, Alegre ML, Bluestone JA, Clark MR. Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial.J Rheumatol. 2002 Sep;29(9):1907-13.

[7] McInnes IB, Illei GG, Danning CL, Yarboro CH, Crane M, Kuroiwa T, Schlimgen R, Lee E, Foster B, Flemming D, Prussin C, Fleisher TA, Boumpas DT. IL-10 improves skin disease and modulates endothelial activation and leukocyte effector function in patients with psoriatic arthritis. J Immunol. 2001 Oct 1;167(7):4075-82.

Ask the Expert Michael D. Lockshin The biggest problem in answering this is the definition of 'early' and 'late' lupus. Some patients have very minor symptoms that persist for years and need almost no treatment; others are very sick from the outset of their very first symptoms. Most people use the term 'early' to denote time, but in lupus the issue is probably one of severity. Clearly, the sooner the disease is recognized, and the sooner treatment is initiated, the less damage will occur. However, early treatment does not necessarily prevent later flares. Patients with SLE follow three types of courses: chronic active (accounting for about half of patient-years), relapsing-remitting, and long-remitting. There's also the concern about what sort of treatment is indicated. In some cases, that means corticosteroids; in others, immunosuppressives are needed, and in still others, anticoagulants. All have dangers associated with them, and it is a judgment call whether to use them or not in given circumstances. For example, even management of asymptomatic patients with anti-cardiolipin antibody is still controversial. There is, in fact, so much variability in the treatment of an individual lupus patient that I cannot provide a clear answer about early or late treatment. However, I do not know of any research suggesting that early treatment prevents later serious flares. (For further treatment information, see Dr. Lockshin's In-Depth Topic Review on SLE.) See the complete article on the Hospital for Special Surgery's web site

Interviews with Experts 

Select the audio version for Dr. Stephen Paget’s interview with Dr. Lockshin on the Hospital for Special Surgery’s web site