Rachelle Buchbinder, Claire Bombardier, Maria Yeung, and Peter Tugwell 1568

Clinical trials are our main source of knowledge about the comparative efficacy of drugs used to treat RA, yet to date there has been no uniformity with which outcomes are measured in different trials. The ACR and OMERACT have proposed a core set of outcome measures to be used in clinical trials. This study confirms the discriminant validity (responsiveness to treatment) of the outcome measures proposed.

Larry W. Moreland, Parks W. Pratt, Maureen D. Mayes, Arnold Postlethwaite, Michael H. Weisman, Thomas Schnitzer, Robert Lightfoot, Leonard Calabrese, David J. Zelinger, James N. Woody, and William J. Koopman 1581

This study demonstrates the lack of efficacy of a depleting anti-CD4 monoclonal antibody (cM-T412) in a cohort of rheumatoid arthritis patients also receiving stable doses of methotrexate. Although the group that received 3 monthly infusions of 50 mg cM-T412 had significant sustained decreases in circulating CD4+ T Iymphocytes, there was no important improvement in clinical measures of disease activity compared with the placebo-treated group.

Michael E. Weinblatt, Peter J. Maddison, Ken J. Bulpitt, Brian L. Hazleman, Murray B. Urowitz, Roger D. Sturrock, Jonathan S. Coblyn, Agnes L. Maier, William R. Spreen, Vasant K. Manna, and Jeffrey M. Johnston 1589

One approach to the treatment of rheumatoid arthritis has been to utilize agents that deplete Iymphocytes, such as the potent humanized monoclonal antibody, CAMPATH-IH. A marked and sustained depletion of peripheral Iymphocytes was observed with infusion of this antibody, but the clinical response was of short duration only. Therefore, the role of depleting monoclonal antibodies as a therapy for rheumatoid arthritis needs to be reevaluated.

Vlastimir Mladenovic, Zlatko Domljan, Blaz Rozman, Ivo Jajic, Dimitrije Mihajlovic, Jovan Dordevic, Milan Popovic, Miroslava Dimitrijevic, Milutin Zivkovic, Giles Campion, Predrag Musikic, Iris Low-Friedrich, Christine Oed, Hildegard Seifert, and Vibeke Strand 1595

Leflunomide is a novel isoxazole drug with immunosuppressive and antiproliferative properties. This report summarizes the findings in a randomized, placebo-controlled, phase II study comparing 3 different doses of leflunomide to placebo in 402 patients with active RA. Randomized, placebo-controlled trials are under way in the US and Europe to further define potential therapeutic effects of leflunomide and compare it to currently utilized DMARDs, methotrexate, and sulfasalazine.

Barry Eibschutz, Stephen M. Baird, Michael H. Weisman, Diane G. Amox, Mary Spellman, Daniel Piacquadio, Carlos J. Carrera, and Dennis A. Carson 1604

Lymphocyte infiltration in inflammatory synovium may be important in inducing and maintaining pathologic changes. 2-chlorodeoxyadenosine (2-CdA) is a selective and potent agent that produces the depletion of Iymphocytes in vivo. Weekly oral administration of 2-CdA in patients with psoriatic arthritis led to selective decreases in Iymphocytes, both in the peripheral circulation and in skin.

Karl Gaffney, John Cookson, David Blake, Adam Coumbe, and Selina Blades 1610

The development of a method for quantifying acute synovial inflammation utilizing gadolinium-enhanced magnetic resonance imaging, which may prove to be of considerable clinical benefit in the management of rheumatoid arthritis, is described. Potential applications of this technique include the pharmacodynamic evaluation of antirheumatic drugs and patient assessment in clinical practice.

Xavier Puéchal, Gerard Said, Pascal Hilliquin, Joel Coste, Chantal Job-Deslandre, Catherine Lacroix, and Charles J. Menkés 1618

This clinicopathologic study of 32 patients with noncompressive neuropathies associated with RA revealed that necrotizing vasculitis is responsible for the different patterns of neuropathy, including mononeuritis multiplex and distal symmetric sensory or sensorimotor neuropathy, which share a similar prognosis. The factors correlated with mortality in this study of rheumatoid vasculitis were, in decreasing order of significance, clinical cutaneous vasculitis, neuropathy involving 3 or 4 limbs, and a depressed C4 level. These variables allow a prognostic assessment to be devised in order to stratify patients to receive more aggressive or less aggressive therapy.

Susan Reisine, Julia McOuillan, and Judith Fifield 1630

Work disability is a major problem affecting a majority of patients with RA. By identifying predictors of work disability in this population, this report contributes to knowledge about ways in which such disability can be prevented or delayed.

Loïc Guillevin, François Lhote, Pascal Cohen, Bernard Jarrousse, Olivier Lortholary, Thierry Généreau, Anne Léon, and Annette Bussel 1638

This study compared corticosteroids and cyclophosphamide alone, versus this regimen plus administration of plasma exchanges, in the treatment of patients with non-hepatitis-related PAN or CSS with factors predicting poor prognosis. The latter regimen did not appear to be more effective than the former, and plasma exchange is thus not recommended as routine first-line treatment of patients with these conditions.

Genaro M. A. Palmieri, Jeno 1. Sebes, Jacob A. Aelion, Mohamed Moinuddin, Morris W. Ray, George C. Wood, and Marvin R. Leventhal 1646

The subjective and objective beneficial effects of 1-12 years of diltiazem treatment in 4 patients with calcinosis are reported. The probable mechanism of action of diltiazem in calcinosis is discussed.

Joan T. Merrill, Eugene Rivkin, Christine Shen, and Robert G. Lahita 1655

Serum from an SLE patient with a history of a cerebrovascular accident was used to isolate a fragment of a gene product with 82So sequence homology to apolipoprotein Al, the major apolipoprotein of high density lipoprotein. Further testing of lupus serum in an ELISA utilizing human apolipoprotein Al as antigen identified 5 more SLE patients with autoantibodies to apolipoprotein Al. These antibodies might represent an independent risk factor for accelerated atherosclerosis in patients with SLE.

Andras Perl, Emanuela Colombo, Huiliang Dai, Rajeev Agarwal, Kenneth A. Mark, Katalin Banki, Bernard J. Poiesz, Paul E. Phillips, Sallie O. Hoch, John D. Reveille, and Frank C. Arnett 1660

This study documents a high prevalence of antibodies to an endogenous retroviral element-encoded nuclear autoantigen, HRES-I, and demonstrates amino acid similarities and immunologic cross-reactivity between HRES-I and a retroviral gag-related region of the 70-kd component of Ul small nuclear RNP. HRES-I antibodies are detectable independently of RNP reactivities in a distinct subset of patients, primarily those who do not have antibodies to Sm, Ro, or La. The presence of HRES-I antibodies identifies a distinct subset of patients in whom autoantigenicity of an endogenous retroviral element may be of pathogenetic, and thereby of diagnostic, significance.

Akihiro Yamaguchi, Naoyuki Tsuchiya, Hiroshi Mitsui, Michiko Shiota, Atsuko Ogawa, Katsushi Tokunaga, Sadayoshi Yoshinoya, Takeo Juji, and Koji Ito 1672

This study demonstrated an association between HLA-B39 and both HLA-B27-negative ankylosing spondylitis and pauciarticular juvenile rheumatoid arthritis in Japanese patients. These results suggest that the structure of the antigen-binding cleft may be important in the development of these diseases.

Lawrence J. Bonassar, Kimberly A. Jeffries, Eliot H. Frank, Vernon L. Moore, Michael W. Lark, Ellen K. Bayne, Joseph McDonnell, Julie Olszewski, William Hagmann, Kevin Chapman, and Alan J. Grodzinsky 1678

The matrix metalloproteinase stromelysin is thought to play a role in normal cartilage turnover and matrix remodeling, as well as in pathologic conditions such as arthritis. While stromelysin has been shown to degrade purified matrix components in solution and dramatically alter the composition and physical properties of cartilage explants in vitro, the effects of stromelysin exposure on intact cartilage in vivo are not well understood. Given that elevated levels of stromelysin are present in the cartilage and synovial fluid of patients with rheumatoid arthritis and osteoarthritis, knowledge of the effects of stromelysin in vivo is an important key to understanding the role of enzymatic degradation in arthritis. These effects were investigated in the present study.

Marco Matucci-Cerinic, Francesco Borrelli, Sergio Generini, Alfredo Cantelmo, Isabella Marcucci, Fabrizio Martelli, Paolo Romagnoli, Stefano Bacci, Angelo Conz, Paolo Marinelli, and Simone Marabini 1687

This study demonstrates the efficacy of somatostatin in reducing inflammation in experimental arthritis. A dosage of 1,000 ,µg was most effective, particularly when compared with triamcinolone acetonide. Thus, intraarticular somatostatin may be suggested as a novel potential drug for use in arthritis.

Lewis McCurdy, W. Winn Chatham, and Warren D. Blackburn, Jr. 1694

This study evaluates a mechanism by which rheumatoid synovial fibroblast adhesion to cartilage is enhanced. These results provide further insights into the understanding of the progression of rheumatoid arthritis.