Rheumatoid Arthritis: Alarcón GS

Soriano ER, Galarza-Maldonado C, Cardiel MH, Pons-Estel BA, Massardo L, Caballero-Uribe CV, Achurra-Castillo AF, Barile-Fabris LA, Chávez-Corrales J, Díaz-Coto JF, Esteva-Spinetti MH, Guibert-Toledano M, Palazuelos FI, Keiserman MW, Lomonte AV, Mota LM, Pineda Villaseñor C, Alarcón GS, Anonymous00427. · Sección Reumatología, Servicio de Clínica Médica, Hospital Italiano de Buenos Aires y Fundación Dr Pedro M. Catoggio para el Progreso de la Reumatología, Buenos Aires, Argentina. · Rheumatology (Oxford). · Pubmed #18463144 links to  free full text

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Alarcón GS. · No affiliation provided · Semin Arthritis Rheum. · Pubmed #11740795 No free full text.

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Gauhar UA, Gaffo AL, Alarcón GS. · Division of Pulmonary and Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, Alabama 35294-3408, USA. · Semin Respir Crit Care Med. · Pubmed #17764060 No free full text.

Abstract: Rheumatoid arthritis (RA) is a systemic disease, characterized by symmetric joint involvement, but it can also affect other organ systems, including the lungs. The better-known pulmonary manifestations of RA are interstitial lung disease, rheumatoid nodules, and pleural effusions. Less common manifestations include bronchiolitis obliterans and crycoarytenoid arthritis. Management of these conditions involves, by and large, supportive pulmonary care and control of the underlying articular process. Other pulmonary manifestations in RA patients can ensue as a result of the treatments used for it, mainly methotrexate. This article discusses the most common pulmonary manifestations of RA and their treatment. A discussion about the increasing impact that cigarette smoking is having on RA is also provided.

Bridges SL, Hughes LB, Mikuls TR, Howard G, Tiwari HK, Alarcón GS, McNicholl JM, Moreland LW. · Departments of Medicine and Microbiology, Division of Clinical Immu-nology and Rheumatology, University of Alabama at Birmingham, 415 Lyons-Harrison Research Building, 701 19th Street South, Birmingham, Alabama 35294-0007, USA. · Clin Exp Rheumatol. · Pubmed #14969066 No free full text.

Abstract: African-Americans have been under-represented in genetic studies of rheumatoid arthritis (RA) susceptibility and severity. Genetic and non-genetic factors influencing the radiographic severity of RA and its response to treatment are poorly understood, particularly in African-Americans. The Consortium for the Longitudinal Evaluation of African-Americans with early RA (CLEAR) Registry, a collaborative effort among four institutions in the southeast USA, will hopefully provide a useful resource to study these issues.

Alarcón GS. · University of Alabama, n615 Medical Education Building, UAB, Birmingham, AL 35294, USA. · Expert Opin Investig Drugs. · Pubmed #11060754 No free full text.

Abstract: In this review the rationale for the possible beneficial effect of tetracycline derivatives for the treatment of rheumatoid arthritis is discussed. Early studies (Sanchez, Skinner et al. and Brown et al. ) and the two open trials of the 1980s are briefly discussed. The three double-blind studies conducted in the 1990s (Kloppenburg et al. , The Netherlands; the MIRA trial, USA and the O'Dell et al., USA) are described in detail. The baseline clinical and demographic data for these patients, as well as the efficacy and toxicity data are described in the text and summarised in tables. The long-term data of the O'Dell et al.'s trial is described. Finally, side effects not observed during the conduct of these trials, but reported to occur in other patients, for example those receiving minocycline for the treatment of acne, are also listed.

Alarcón GS. · Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA. · Immunopharmacology. · Pubmed #10878293 No free full text.

Abstract: Aminopterine, a precursor of methotrexate (MTX), was first used for the treatment of rheumatoid arthritis (RA) in 1951 [Gubner, R., 1951. Therapeutic suppression of tissue reactivity: I. Comparison of the effects of cortisone and aminopterin. Am. J. Med. Sci. 221, 169-175; Gubner, R., August, S., Ginsberg, V., 1951. Therapeutic suppression of tissue reactivity: II. Effect of aminopterin in rheumatoid arthritis and psoriasis. Am. J. Med. Sci. 221, 176-182.]. Corticosteroids, and to some extent cyclophosphamide, took MTX out of the rheumatologist's armamentarium until the late 1970s-early 1980s when the toxic profile of these compounds became apparent. By the mid 1980s, four randomized clinical trials (RCTs) had proven beyond doubt the beneficial effects of MTX when administered to patients with established disease who had failed to respond to other compounds such as gold salts and D-penicillamine [Thompson, R.N., Watts, C., Edelman, J., Esdaile, J., and Russell, A.S., 1984. A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. J. Rheumatol. 11, 760-763; Andersen, P.A., West, S.G., O'Dell, J.R., Via, C.S., Claypool, R.G., and Kotzin, B.L., 1985. Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study. Ann. Intern. Med. 103, 489-496; Weinblatt, M.E., Coblyn, J.S., Fox, D.A., Fraser, P.A., Holdsworth, D.E., Glass, D.N., and Trentham, D.E., 1985. Efficacy of low-dose methotrexate in rheumatoid arthritis. N. Engl. J. Med. 312, 818-822; Williams, H.J., Willkens, R.F., Samuelson, C.O.J., Alarcón, G.S., Guttadauria, M., Yarboro, C., Polisson, R.P., Weiner, S.R., Luggen, M.E., Billingsley, L.M., Dahl, S.L., Egger, M.J., Reading, J.C., and Ward, J.R., 1985. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum. 28, 721-730.]. Subsequently, these four trials were included in a meta-analysis and the drug was approved by the Food and Drug Administration for use in RA [Health and Public Policy Committee, H.P.P.C. and American College Physicians, A.C.P., 1987. Methotrexate in rheumatoid arthritis. Ann. Intern. Med. 107, 418-419; Paulus, H.E., 1986. FDA Arthritis Advisory Committee meeting: Methotrexate; guidelines for the clinical evaluation of antiinflammatory drugs; DMSO in scleroderma. Arthritis Rheum. 29, 1289-1290; Tugwell, P., Bennett, K., and Gent, M., 1987. Methotrexate in rheumatoid arthritis. Indications, contraindications, efficacy, and safety. Ann. Intern. Med. 107, 358-366.]. Since then, rheumatologists have become aware of what Pincus et al. have called "the side effects" of RA comparing the morbidity and mortality caused by RA with that potentially caused by medications used to treat this disease [Pincus, T. and Callahan, L.F., 1993. The "side effects" of rheumatoid arthritis: joint destruction, disability and early mortality. Br. J. Rheumatol. 32, 28-37.]. Thus, during the 1990s the use of MTX for the treatment of RA became generalized [O'Dell, J.R., 1997. Methotrexate use in rheumatoid arthritis. Rheum. Dis. Clin. N Am. 23, 779-796 (a); Bannwarth, B., Vernhes, J., Schaeverbeke, T., and Dehais, J., 1995. The facts about methotrexate in rheumatoid arthritis. Rev. Rhum. 62, 471-473 (b); Bologna, C., Jorgensen, C., and Sany, J., 1997a. Methotrexate as the initial second-line disease modifying agent in the treatment of rheumatoid arthritis patients. Clin. Exp. Rheumatol. 15, 597-601; Bologna, C., Viu, P. (ABSTRACT TRUNCATED)

Alarcón GS. · Arthritis and Musculoskeletal Diseases Center, University of Alabama School of Medicine, Birmingham 35294, USA. · Postgrad Med. · Pubmed #10223089 No free full text.

Abstract: Rheumatoid arthritis is a painful, chronic disease that affects an estimated 2 million Americans. Although no single pharmacologic agent is completely effective against the disease, some patients have shown significant improvement when treated with minocycline. Dr Alarcón summarizes the outcomes of studies to date and offers her recommendations.

Morgan SL, Oster RA, Lee JY, Alarcón GS, Baggott JE. · University of Alabama at Birmingham, 35294-1270, USA. · Arthritis Rheum. · Pubmed #15476202 links to  free full text

Abstract: OBJECTIVE: To determine if folinic acid supplementation during methotrexate (MTX) therapy for rheumatoid arthritis (RA) reduces both urinary 5-aminoimidazole-4-carboxamide (AICA) and urinary adenosine excretion more than does folic acid supplementation. AICA and adenosine are markers for MTX interference with purine metabolism. METHODS: Forty patients with RA who received MTX for 6 weeks were randomized to receive either daily folic acid or folinic acid supplements during an additional week of MTX therapy. Colorimetric and radioimmunocompetition assays were used to measure 24-hour urinary AICA and adenosine excretion levels, respectively. RESULTS: At the end of 6 weeks, 24-hour urinary levels of AICA, but not adenosine, were elevated as compared with baseline levels (i.e., prior to MTX therapy). Folinic acid, but not folic acid, supplementation normalized urinary AICA levels during MTX therapy. Relatively high urinary levels of AICA were correlated with reduced disease activity. No similar correlations were seen with urinary adenosine levels. CONCLUSION: The blockade of purine nucleotide biosynthesis by MTX at the AICA ribonucleotide transformylase-catalyzed step may be related to the efficacy of MTX, and this blockade is effectively relieved by folinic acid, but not by folic acid, supplementation.

Kelley JM, Hughes LB, Faggard JD, Danila MI, Crawford MH, Edberg Y, Padilla MA, Tiwari HK, Westfall AO, Alarcón GS, Conn DL, Jonas BL, Callahan LF, Smith EA, Brasington RD, Allison DB, Kimberly RP, Moreland LW, Edberg JC, Bridges SL. · University of Alabama at Birmingham, Birmingham, AL, USA. · PLoS Genet. · Pubmed #19300490 links to  free full text

Abstract: Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is approximately 1.0%; RA is purportedly less common in black Africans, with little known about its prevalence in African Americans. We sought to determine if CTLA4 polymorphisms are associated with RA in African Americans. We performed a 2-stage analysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patients and 712 African American controls using Illumina and TaqMan platforms. The minor allele (G) of the rs231778 SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462 x 10(-26), Fisher's exact). The presence of the G allele was associated with a substantially reduced odds ratio (OR) of having RA (AG+GG genotypes vs. AA genotype, OR 0.19, 95% CI: 0.13-0.26, p = 2.4 x 10(-28), Fisher's exact), suggesting a protective effect. This SNP is polymorphic in the African population (minor allele frequency [MAF] 0.09 in the Yoruba population), but is very rare in other groups (MAF = 0.002 in 530 Caucasians genotyped for this study). Markers associated with RA in populations of European ancestry (rs3087243 [+60C/T] and rs231775 [+49A/G]) were not replicated in African Americans. We found no confounding of association for rs231778 after stratifying for the HLA-DRB1 shared epitope, presence of anti-cyclic citrullinated peptide antibody, or degree of admixture from the European population. An African ancestry-specific genetic variant of CTLA4 appears to be associated with protection from RA in African Americans. This finding may explain, in part, the relatively low prevalence of RA in black African populations.

Wolfe F, Petri M, Alarcón GS, Goldman J, Chakravarty EF, Katz RS, Karlson EW. · National Data Bank for Rheumatic Diseases, 1035 N. Emporia, Suite 288, Wichita, KS 67214, USA. · J Rheumatol. · Pubmed #19004039 No free full text.

Abstract: OBJECTIVE: To determine if fibromyalgia (FM) or fibromyalgia-ness (the tendency to respond to illness and psychosocial stress with fatigue, widespread pain, general increase in symptoms, and similar factors) is increased in patients with compared to those without systemic lupus erythematosus (SLE); to determine whether FM or fibromyalgia-ness biases the SLE Activity Questionnaire (SLAQ); and to determine if the SLAQ is overly sensitive to FM symptoms. METHODS: We developed a 16-item SLE Symptom Scale (SLESS) modeled on the SLAQ and used that scale to investigate the relation between SLE symptoms and fibromyalgia-ness in 23,321 patients with rheumatic disease. FM was diagnosed by survey FM criteria, and fibromyalgia-ness was measured using the Symptom Intensity (SI) Scale. As comparison groups, we combined patients with rheumatoid arthritis and noninflammatory rheumatic disorders into an "arthritis" group and also utilized a physician-diagnosed group of patients with FM. RESULTS: FM was identified in 22.1% of SLE and 17.0% of those with arthritis. The SI scale was minimally increased in SLE. The correlation between SLAQ and SLESS was 0.738. SLESS/SLAQ scale items (Raynaud's phenomenon, rash, fever, easy bruising, hair loss) were significantly more associated with SLE than FM, while the reverse was true for headache, abdominal pain, paresthesias/stroke, fatigue, cognitive problems, and muscle pain or weakness. There was no evidence of disproportionate symptom-reporting associated with fibromyalgia-ness. Self-reported SLE was associated with an increased prevalence of FM that was unconfirmed by physicians, compared to SLE confirmed by physicians. CONCLUSION: The prevalence of FM in SLE is minimally increased compared with its prevalence in patients with arthritis. Fibromyalgia-ness does not bias the SLESS and should not bias SLE assessments, including the SLAQ.

Gaffo AL, Alarcón GS. · Division of Clinical Immunology and Rheumatology, Department of Medicine/Rheumatology, University of Alabama at Birmingham, 510 20th St S, Faculty Office Tower, Room 830, Birmingham, AL 35294-3408. · Arch Intern Med. · Pubmed #18809822 No free full text.

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Hughes LB, Morrison D, Kelley JM, Padilla MA, Vaughan LK, Westfall AO, Dwivedi H, Mikuls TR, Holers VM, Parrish LA, Alarcón GS, Conn DL, Jonas BL, Callahan LF, Smith EA, Gilkeson GS, Howard G, Moreland LW, Patterson N, Reich D, Bridges SL. · University of Alabama at Birmingham 35294-2182, USA. · Arthritis Rheum. · Pubmed #18240241 links to  free full text

Abstract: OBJECTIVE: To determine whether shared epitope (SE)-containing HLA-DRB1 alleles are associated with rheumatoid arthritis (RA) in African Americans and whether their presence is associated with higher degrees of global (genome-wide) genetic admixture from the European population. METHODS: In this multicenter cohort study, African Americans with early RA and matched control subjects were analyzed. In addition to measurement of serum anti-cyclic citrullinated peptide (anti-CCP) antibodies and HLA-DRB1 genotyping, a panel of >1,200 ancestry-informative markers was analyzed in patients with RA and control subjects, to estimate the proportion of European ancestry. RESULTS: The frequency of SE-containing HLA-DRB1 alleles was 25.2% in African American patients with RA versus 13.6% in control subjects (P = 0.00005). Of 321 patients with RA, 42.1% had at least 1 SE-containing allele, compared with 25.3% of 166 control subjects (P = 0.0004). The mean estimated percent European ancestry was associated with SE-containing HLA-DRB1 alleles in African Americans, regardless of disease status (RA or control). As reported in RA patients of European ancestry, there was a significant association of the SE with the presence of the anti-CCP antibody: 86 (48.9%) of 176 patients with anti-CCP antibody-positive RA had at least 1 SE allele, compared with 36 (32.7%) of 110 patients with anti-CCP antibody-negative RA (P = 0.01, by chi-square test). CONCLUSION: HLA-DRB1 alleles containing the SE are strongly associated with susceptibility to RA in African Americans. The absolute contribution is less than that reported in RA among populations of European ancestry, in which approximately 50-70% of patients have at least 1 SE allele. As in Europeans with RA, the SE association was strongest in the subset of African American patients with anti-CCP antibodies. The finding of a higher degree of European ancestry among African Americans with SE alleles suggests that a genetic risk factor for RA was introduced into the African American population through admixture, thus making these individuals more susceptible to subsequent environmental or unknown factors that trigger the disease.

Mikuls TR, Hughes LB, Westfall AO, Holers VM, Parrish L, van der Heijde D, van Everdingen M, Alarcón GS, Conn DL, Jonas B, Callahan LF, Smith EA, Gilkeson G, Howard G, Moreland LW, Bridges SL. · Department of Medicine, University of Nebraska Medical Center and Omaha VA Medical Center, Omaha, NE 68198-6270, USA. · Ann Rheum Dis. · Pubmed #18198196 No free full text.

Abstract: OBJECTIVE: To examine the association of smoking with clinical and serological features in African Americans with recent-onset rheumatoid arthritis (RA) and to explore whether this association is dependent on the presence of the HLA-DRB1 shared epitope (SE). METHODS: In African Americans with recent-onset RA (n = 300), we examined the association of cigarette smoking (current versus past versus never and pack-years of exposure) with anti-cyclic citrullinated peptide antibody, rheumatoid factor (RF) (IgM and IgA), rheumatoid nodules and baseline radiographic erosions using logistic and cumulative logistic regression (adjusting for SE status). We also examined for evidence of interaction between smoking status and SE for all outcomes. RESULTS: Although there was no association with RF-IgA seropositivity, current smokers were approximately twice as likely as never smokers to have higher IgA-RF concentrations (based on tertiles; OR = 1.74; 95% CI 1.05 to 2.88) and nodules (OR = 2.43; 95% CI 1.13 to 5.22). These associations were most pronounced in those with more than 20 pack-years of exposure. There was no association of smoking status or cumulative tobacco exposure with anti-cyclic citrullinated peptide antibody, IgM-RF or radiographic erosions. There was also no evidence of a biological or statistical SE-smoking interaction for any of the outcomes examined. CONCLUSIONS: This is the first study to systematically examine the association of cigarette smoking with RA-related features in African Americans. Cigarette smoking is associated with both subcutaneous nodules and higher serum concentrations of IgA-RF in African Americans with RA, associations that may have important implications for long-term outcomes in this population.

Bajaj S, Lopez-Ben R, Oster R, Alarcón GS. · Division of Clinical Immunology and Rheumatology, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, USA. · Skeletal Radiol. · Pubmed #17033852 No free full text.

Abstract: OBJECTIVE: To evaluate and compare sequential ultrasound exams (US) with power-Doppler (PD) to radiography for the detection of synovitis and erosions in patients with early RA. METHODS: Radiographs and US with PD of the hands and feet were performed at baseline and 6+/- 2 months afterwards in 21 early RA patients. Their mean (range) age was 42.6 (21-81) years and the female/male ratio was 4:3; mean disease duration was 9 (1-28) months. Joints assessed were bilateral 2nd and 5th MCPs, 5th MTPs and the most swollen PIP in each hand, for a total of eight joints per patient. Radiographs (PA, lateral and pronated oblique) were read for erosions using the method of Sharp/van der Heijde. On US, erosions were defined as cortical defects greater than 2 mm in diameter with an irregular floor. Synovitis was rated as +1 (increase in joint fluid without synovial hyperemia), +2 (mild blood flow), +3 (moderate blood flow), and +4 (severe blood flow). Two blinded trained assessors read all images. RESULTS: US detected 15 erosions in 10 patients at baseline and 31 erosions in 12 patients on follow-up; radiographs could detect only one erosion at baseline and five erosions in three patients on follow-up. PD detected synovitis in all patients at baseline and on follow-up. Of the joints found to have synovitis, 64% were identified as such at baseline and 38% on follow-up. CONCLUSIONS: Sequential US can determine disease progression in patients with early RA. Such data may allow the clinician to treat RA patients earlier in the hope of preventing joint damage.

Mikuls TR, Holers VM, Parrish L, Kuhn KA, Conn DL, Gilkeson G, Smith EA, Kamen DL, Jonas BL, Callahan LF, Alarcón GS, Howard G, Moreland LW, Bridges SL. · University of Nebraska Medical Center, Omaha Veterans Administration Medical Center, Omaha, NE, USA. · Arthritis Rheum. · Pubmed #16948136 links to  free full text

This publication has no abstract.

Alarcón GS. · The Faculty of Office Towers, University of Alabama at Birmingham, in Birmingham, Alabama 35294-3408, USA. · Nat Clin Pract Rheumatol. · Pubmed #16932705 No free full text.

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Hughes LB, Beasley TM, Patel H, Tiwari HK, Morgan SL, Baggott JE, Saag KG, McNicholl J, Moreland LW, Alarcón GS, Bridges SL. · Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 415 Lyons-Harrison Research Building, Birmingham, AL 35294-0007, USA. · Ann Rheum Dis. · Pubmed #16439441 No free full text.

Abstract: BACKGROUND: The anti-folate drug methotrexate (MTX) is commonly used to treat rheumatoid arthritis. OBJECTIVE: To determine the allele frequencies of five common coding single-nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene in African-Americans and Caucasians with rheumatoid arthritis and controls to assess whether there are differences in allele frequencies among these ethnic or racial groups and whether these SNPs differentially affect the efficacy or toxicity of MTX. METHODS: Allele frequencies in the 677, 1298 and 3 additional SNPs in the MTHFR coding region in 223 (193 Caucasians and 30 African-Americans) patients with rheumatoid arthritis who previously participated in one of two prospective clinical trials were characterised, and genotypes were correlated with the efficacy and toxicity of MTX. Another 308 subjects with rheumatoid arthritis who participated in observational studies, one group predominantly Caucasian and the other African-American, as well as 103 normal controls (53 African-Americans and 50 Caucasians) were used to characterise allele frequencies of these SNPs and their associated haplotypes. RESULTS: Significantly different allele frequencies were seen in three of the five SNPs and haplotype frequencies between Caucasians and African-Americans. Allele frequencies were similar between patients with rheumatoid arthritis and controls of the same racial or ethnic group. Frequencies of the rs4846051C, 677T and 1298C alleles were 0.33, 0.11 and 0.13, respectively, among African-Americans with rheumatoid arthritis. Among Caucasians with rheumatoid arthritis, these allele frequencies were 0.08 (p<0.001 compared with African-Americans with rheumatoid arthritis), 0.30 (p = 0.002) and 0.34 (p<0.001), respectively. There was no association between SNP alleles or haplotypes and response to MTX as measured by the mean change in the 28-joint Disease Activity Score from baseline values. In Caucasians, the 1298 A (major) allele was associated with a significant increase in MTX-related adverse events characteristic of a recessive genetic effect (odds ratio 15.86, 95% confidence interval 1.51 to 167.01; p = 0.021), confirming previous reports. There was an association between scores of MTX toxicity and the rs4846051 C allele, and haplotypes containing this allele, in African-Americans, but not in Caucasians. CONCLUSIONS: : These results, although preliminary, highlight racial or ethnic differences in frequencies of common MTHFR SNPs. The MTHFR 1298 A and the rs4846051 C alleles were associated with MTX-related adverse events in Caucasians and African-Americans, respectively, but these findings should be replicated in larger studies. The rs4846051 SNP, which is far more common in African-Americans than in Caucasians, can also be proved to be a useful ancestry informative marker in future studies on genetic admixture.

Alarcón GS, Lopez-Ben R, Moreland LW. · No affiliation provided · Arthritis Rheum. · Pubmed #12124884 links to  free full text

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Morgan SL, Baggott JE, Bernreuter WK, Gay RE, Arani R, Alarcón GS. · Department of Nutrition Sciences, University of Alabama at Birmingham, 35294-3360, USA. · J Rheumatol. · Pubmed #11469449 No free full text.

Abstract: OBJECTIVE: To investigate the dose response relationships of methotrexate (MTX) therapy in rat adjuvant arthritis (AA), an animal model of rheumatoid arthritis (RA). METHODS: Female Lewis rats were fed a defined diet and were treated with 0, 0.3, 1, 2, 3, 5, and 10 mg MTX per week beginning 3 days after adjuvant injection and lasting 6 weeks. The presence or absence of arthritis, and its degree were measured by hindpaw edema scores, ankle widths, and radiographic and histopathologic scores. RESULTS: The 2, 3, 5, and 10 mg MTX per week doses resulted in deaths before the end of the protocol and suppressed normal body weight gain. Tissue destruction, measured by radiographic and histopathologic scores, was reduced in a dose dependent manner with increasing MTX dose. Suppression of inflammation, measured by ankle widths and radiographic and histopathologic scores, reached a maximum at the 1 mg MTX dose and declined at higher doses. CONCLUSIONS: Suppression of tissue destruction and inflammation in rat AA does not occur in a concerted fashion as the dose of MTX increases. The implications of these findings to human disease remain to be determined.

Alarcón GS, Bartolucci AA. · University of Alabama at Birmingham School of Medicine, 35294, USA. · J Rheumatol. · Pubmed #10685828 No free full text.

Abstract: Radiographic studies of methotrexate (MTX) treated and minocycline treated patients with rheumatoid arthritis (RA) are reviewed. A formal metaanalysis of publications of RA treated with MTX was undertaken at the time when MTX was used for patients with established RA. Thus the conclusions of that metaanalysis may not be applicable to patients treated with MTX earlier in the course of their disease. On the other hand, there are no sufficient data to conduct a formal metaanalysis of patients with RA treated with minocycline.

Tilley BC, Pillemer SR, Heyse SP, Li S, Clegg DO, Alarcón GS. · Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston 29425, USA. · Arthritis Rheum. · Pubmed #10513802 links to  free full text

Abstract: OBJECTIVE: To evaluate global statistical tests (GSTs) of treatment effectiveness for rheumatoid arthritis (RA) trials measuring multiple outcomes. METHODS: Using outcome measures from American College of Rheumatology (ACR) core set variables available in 3 RA trials, GSTs were calculated using the O'Brien ranking procedure and a procedure for binary data. GSTs take correlations among outcomes into account. Power calculations using 1 trial data set provide comparisons of GSTs and ACR criteria for improvement. RESULTS: Spearman correlations among outcomes ranged from 0.21 to 0.73. Erythrocyte sedimentation rate had the lowest correlation with other outcomes in all 3 trials. Within a trial, joint swelling and joint tenderness or patient and physician assessment had the highest correlations, depending on the trial. Results were consistent with results using the ACR criteria, although the GST was more powerful. CONCLUSION: GSTs are a useful tool for comparing treatment effects across multiple clinically meaningful outcome measures. The GST allows easy inclusion of validated, reliable new measures that are not a part of ACR criteria, such as quality of life, and can be computed with or without selecting a cutoff point defining patient improvement. GSTs should be considered for rheumatic disease treatment trials.

Alarcón GS, Tilley BC, Li S, Fowler SE, Pillemer SR. · University of Alabama, Birmingham 35294-3296, USA. · J Rheumatol. · Pubmed #10332969 No free full text.

Abstract: OBJECTIVE: To determine the comparability of a text to a mannequin format for the assessment of joint counts (JC) among patients with rheumatoid arthritis (RA) participating in a randomized clinical trial (RCT). METHODS: A subgroup of patients participating in the MIRA (Minocycline in RA) RCT completed self-administered JC and joint scores (JS), which were compared to those of a trained assessor. RESULTS: JC and JS data were consistently higher for the patient than for the assessor. Higher correlations were obtained for JC than for JS. CONCLUSION: Our data suggest JC can be used in the context of clinical trials or in the clinical setting, but are not interchangeable with trained assessor JC.

Calvo FA, Calvo A, Berrocal A, Pevez C, Romero F, Vega E, Cusi R, Visaga M, De La Cruz RA, Alarcón GS. · Department of Medicine, The University of Alabama at Birmingham, 35294, USA. · J Rheumatol. · Pubmed #10090158 No free full text.

Abstract: OBJECTIVE: To test the reliability and validity of a self-administered 36 joint count developed after the Rapid Assessment of Disease Activity in Rheumatology (RADAR) questionnaire for assessing pain/tenderness. METHODS: Two self-administered formats (mannequin and text) were evaluated in 60 patients with rheumatoid arthritis (RA). Reliability between both formats was tested by Spearman rank correlation. Criterion validity/accuracy was tested by Spearman correlation coefficient between each self-report format and a joint count performed by a physician. Construct validity was ascertained by correlation of each format with other variables of disease activity. RESULTS: Reliability between the 2 formats was high (R = 0.94). Correlations between each format and the physician's joint count were also high (R = 0.77 for mannequin, 0.75 for text). Patients consistently rated their joint pain/tenderness higher than the physician (means 29, 27, and 12 for text, mannequin, and physician, respectively; p < 0.01). Construct validity of the text, mannequin, and physician formats compared with the modified Health Assessment Questionnaire showed R = 0.61, 0.65, 0.63; with Steinbrocker functional class R = 0.41, 0.46, 0.56; with pain R = 0.59, 0.61, 0.62; with global evaluation R = 0.66, 0.71, 0.84; and with morning stiffness R = 0.64, 0.59, 0.60, respectively. CONCLUSION: Although both self-administered formats exhibited adequate reliability and construct validity, a systematic difference between patient and physician/trained assistant performed joint counts was observed, with patients consistently rating their pain/tenderness higher. We thus do not believe they can replace standard physician/trained assistant evaluation in obtaining clinical research data in rheumatology.

Rich E, Moreland LW, Alarcón GS. · Department of Medicine, University of Alabama at Birmingham, 35294, USA. · J Rheumatol. · Pubmed #9972955 No free full text.

Abstract: OBJECTIVE: To determine disease progression in patients with rheumatoid arthritis (RA) using methotrexate (MTX) as the first disease modifying antirheumatic drug (DMARD). METHODS: Patients with RA treated with MTX as their first DMARD and in whom hand/wrist radiographs prior to MTX administration had been obtained and who had received MTX for at least 10 months were evaluated radiographically for disease progression. Coded radiographs were read for erosions by 2 experienced readers using the modified method of Sharp. Erosion scores and rate of progression (per month) were calculated. RESULTS: Of 24 patients studied, baseline radiographs showed erosions (one or more) in 11 and none in 13. Patients with and without erosions at baseline had comparable demographic and clinical features, although patients with erosions had longer disease duration and higher rheumatoid factor positivity than those without erosions (statistically nonsignificant, however). Half of all patients showed no progression; 73% of those patients with erosions at baseline but only 31% of those without erosions at baseline progressed (p = 0.049); progression rates were 0.017 (+/-0.033) and 0.049 (+/-0.078) for the 2 groups (p = 0.040). CONCLUSION: Patients with RA starting MTX before erosions have occurred are less likely to develop them; these patients also experienced a lesser degree of disease progression than patients who started MTX with erosions already present.

Morgan SL, Baggott JE, Alarcón GS. · No affiliation provided · Arthritis Rheum. · Pubmed #16646062 links to  free full text

This publication has no abstract.