Rheumatoid Arthritis: Furst D

Lipani JA, Strand V, Woodworth T, Furst D, Singh G, Johnson K, Day R, Brooks P. · No affiliation provided · J Rheumatol. · Pubmed #10782801 No free full text.

This publication has no abstract.

Lipani JA, Strand V, Johnson K, Woodworth T, Furst D, Singh G, Day R, Brooks P, Anonymous00241. · Department of Medicine, Standford Universiity, Palo Alto, CA, USA. · J Rheumatol. · Pubmed #11361208 No free full text.

Abstract: This paper proposes the creation of an objectively acquired reference database to more accurately characterize the incidence and longterm risk of relatively infrequent, but serious, adverse events. Such a database would be maintained longitudinally to provide for ongoing comparison with new rheumatologic drug safety databases collecting the occurrences and treatments of rare events. We propose the establishment of product-specific registries to prospectively follow a cohort of patients with rheumatoid arthritis (RA) who receive newly approved therapies. In addition, a database is required of a much larger cohort of RA patients treated with multiple second line agents of sufficient size to enable case-controlled determinations of the relative incidence of rare but serious events in the treated (registry) versus the larger disease population. The number of patients necessary for agent-specific registries and a larger patient population adequate to supply a matched case-control cohort will depend upon estimates of the detectability of an increased incidence over background. We suggest a system to carry out this proposal that will involve an umbrella organization, responsible for establishment of this large patient cohort, envisioned to be drawn from around the world.

Figueroa F, Braun-Moscovici Y, Khanna D, Voon E, Gallardo L, Luinstra D, Pina X, Henstorf G, Laurence S, Neiman R, Furst D. · Department of Medicine, Universidad de los Andes, Santiago de Chile, Chile. · J Rheumatol. · Pubmed #17216678 No free full text.

Abstract: OBJECTIVE: To examine whether self-assessment of tender and swollen joints by patients with rheumatoid arthritis (RA) can be used to evaluate changes in disease activity instead of joint counts by physicians. METHODS: Eighty-two patients with RA taking part in controlled studies were recruited for investigation. The patient's self-assessment of joint tenderness and swelling was completed both before and 30 minutes after examination by a physician. Examinations of tender and swollen joints by a rheumatologist were performed at baseline and 3 months later. The correlations and verification of agreement of these clinical assessments were analyzed. RESULTS: Within-patient and patient-physician correlations for joint tenderness counts were high (r = 0.96 and 0.78, respectively). Patient-physician correlation for joint swelling counts was still significant, although much lower (r = 0.34). Patients' and physicians' estimations of the change in disease activity over 3 months did not differ (p > 0.76 for all comparisons). CONCLUSION: Joint tenderness counts were consistent when comparing intra-patient and patient-physician assessments, while joint swelling counts were poorly correlated. Patient and physician assessments of change over 3 months were parallel and similar for joint tenderness count. Self-administered tender joint counts might be a useful tool to evaluate the response to therapy in RA.

Maini RN, Breedveld FC, Kalden JR, Smolen JS, Furst D, Weisman MH, St Clair EW, Keenan GF, van der Heijde D, Marsters PA, Lipsky PE, Anonymous00061. · Kennedy Institute of Rheumatology, Hammersmith, London, UK. · Arthritis Rheum. · Pubmed #15077287 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy and safety of repeated administration of infliximab plus methotrexate (MTX) over a 2-year period in patients with rheumatoid arthritis (RA) who previously experienced an incomplete response to MTX. METHODS: Four hundred twenty-eight patients were randomly assigned to receive MTX plus placebo or infliximab at a dose of 3 or 10 mg/kg plus MTX for 54 weeks, with an additional year of followup. The protocol was later amended to allow for continued treatment during the second year. Of 259 patients who entered the second year of treatment, 216 continued to receive infliximab plus MTX for 102 weeks. Ninety-four of these 259 patients experienced a gap in therapy of >8 weeks before continuing therapy. Infusions were administered at weeks 0, 2, and 6, followed by treatment every 4 weeks or every 8 weeks (alternating with placebo infusions in the interim 4-week visits) at a dose of 3 or 10 mg/kg for a total of 102 weeks (including the gap in therapy). For safety and efficacy assessments, data on the patients who were randomized to receive treatment, irrespective of whether treatment was administered for 102 weeks, were evaluated using all actual observations available. The efficacy measures included the Health Assessment Questionnaire (HAQ) (physical function), Short Form 36 health survey (SF-36) (health-related quality of life), total radiographic scores (structural damage), and the American College of Rheumatology 20% improvement criteria (ACR20) (signs and symptoms). RESULTS: The infliximab plus MTX regimens resulted in significantly greater improvement in HAQ scores (P < or = 0.006) and SF-36 physical component summary scores (P < or = 0.011) compared with the MTX-only group. There also was stability in the SF-36 mental component summary score among patients who received the infliximab plus MTX regimens. Median changes from baseline to week 102 in the total radiographic score were 4.25 for patients who received the MTX-only regimen and 0.50 for patients who received the infliximab plus MTX regimen. The proportion of patients achieving an ACR20 response at week 102 varied from 40% to 48% for the infliximab plus MTX groups compared with 16% for the MTX-only group. CONCLUSION: Throughout 102 weeks of therapy, infliximab plus MTX provided significant, clinically relevant improvement in physical function and quality of life, accompanied by inhibition of progressive joint damage and sustained improvement in the signs and symptoms of RA among patients who previously had an incomplete response to MTX alone.

Kavanaugh A, Genovese M, Baughman J, Kivitz A, Bulpitt K, Olsen N, Weisman M, Matteson E, Furst D, van Vollenhoven R, Anderson J, Cohen S, Wei N, Meijerink J, Jacobs C, Mocci S. · Division of Rheumatology, Allergy and Immunology, University of California, San Diego, San Diego, CA 92037-0943, USA. · J Rheumatol. · Pubmed #12610799 No free full text.

Abstract: OBJECTIVE: Human cartilage glycoprotein 39 (HC gp-39) appears to be a relevant autoantigen in patients with rheumatoid arthritis (RA). Administration of major histocompatibility complex (MHC) Class II complexed antigens without requisite costimulatory signals can induce immunologic tolerance. We evaluated the safety, pharmacokinetics, and preliminary efficacy of AG4263 in patients with RA. AG4263 is a soluble complex of native HLA-DR4 (beta*0401) complexed to Org 36601, a 13-mer peptide derived from HC gp-39 (also referred to as CDP263). METHODS: Thirty-one HLA-DRB1*0401 positive patients with persistent RA disease activity despite concurrent methotrexate were randomized to 7 infusions of AG4263 (n = 24) or placebo (n = 7) over 6 weeks. The initial dose of 0.5 micro g/kg was escalated in subsequent cohorts to a maximum of 150 micro g/kg. Safety analyses included recording of adverse events and measurement of CD4/CD8 counts, reactivity to recall antigens, and development of antibodies to HLA-DR4. Efficacy was assessed using the Paulus 20 criteria. RESULTS: Treatment was well tolerated, with injection site reaction the most common adverse event. There was no loss of reactivity to recall antigens, change in cell counts, or antibodies to HLA-DR. The mean half-life of AG4263 was 12.5 h. Some evidence of clinical response was seen; responses were more common among patients receiving the highest doses of AG4263 and among those with baseline T cell reactivity to CDP263. CONCLUSION: AG4263 was safe, well tolerated, and without evidence of generalized immune suppression. Along with the observed trend toward clinical efficacy, the results suggest that this therapeutic approach warrants further investigation in patients with RA.

Cohen S, Cannon GW, Schiff M, Weaver A, Fox R, Olsen N, Furst D, Sharp J, Moreland L, Caldwell J, Kaine J, Strand V. · St Paul Medical Center, Dallas, TX, USA. · Arthritis Rheum. · Pubmed #11592358 links to  free full text

Abstract: OBJECTIVE: Three 6-12-month, double-blind, randomized, controlled trials have shown leflunomide (LEF; 20 mg/day, loading dose 100 mg x 3 days) to be effective and safe for the treatment of rheumatoid arthritis (RA). This analysis of the North American trial assessed whether the clinical benefit evident at month 12 was sustained over 24 months of treatment with LEF as compared with the efficacy and safety of methotrexate (MTX), an equivalent disease-modifying antirheumatic drug, at 24 months. METHODS: The year-2 cohort, comprising patients continuing into the second year of treatment with > or = 1 dose of study medication and > or = 1 followup visit after week 52, consisted of 235 patients (LEF n = 98; placebo n = 36; MTX n = 101). The mean (+/- SD) maintenance dose of LEF was 19.6 +/- 1.99 mg/day in year 2 and that of MTX was 12.6 +/- 4.69 mg/week. Statistical analyses used an intent-to-treat (ITT) approach. Statistical comparisons of the active treatments only were prospectively defined in the protocol. RESULTS: In total, 85% and 79% of LEF and MTX patients, respectively, who entered year 2 completed 24 months of treatment. From month 12 to month 24, the American College of Rheumatology improvement response rates of > or = 20% (LEF 79% versus MTX 67%; P = 0.049), > or = 50% (LEF 56% versus MTX 43%; P = 0.053), and > or = 70% (LEF 26% versus MTX 20%; P = 0.361) were sustained in both of the active treatment groups. The mean change in total Sharp radiologic damage scores at year 2 compared with year 1 and baseline (LEF 1.6 versus MTX 1.2) showed statistically equivalent sustained retardation of radiographic progression in the active treatment groups. Maximal improvements evident at 6 months in the Health Assessment Questionnaire (HAQ) disability index (HAQ DI) and the physical component score of the Medical Outcomes Survey 36-item short form were sustained over 12 months and 24 months; improvement in the HAQ DI with LEF4(-0.60) was statistically significantly superior to that with MTX (-0.37) at 24 months (P = 0.005). Over 24 months in the ITT cohort, serious treatment-related adverse events were reported in 1.6% of the LEF-treated patients and 3.7% of the MTX-treated patients. Frequently reported adverse events included upper respiratory tract infections, diarrhea, nausea and vomiting, rash, reversible alopecia, and transient liver enzyme elevations. CONCLUSION: The safety and efficacy of LEF and MTX were maintained over the second year of this 2-year trial. Both active treatments retarded radiographic progression over 24 months. LEF was statistically significantly superior to MTX in improving physical function as measured by the HAQ DI over 24 months of treatment. Results indicate that LEF is a safe and effective initial treatment for active RA, with clinical benefit sustained over 2 years of treatment without evidence of new or increased toxicity.

Furst D, Felson D, Thoren G, Gendreau RM. · Virginia Mason Research Center and University of Washington, Seattle 98101, USA. · Ther Apher. · Pubmed #11111818 No free full text.

Abstract: A double-blind, randomized, placebo controlled study was conducted to determine the efficacy of a promising immunoadsorption treatment device containing staphylococcal protein A (Prosorba Immunoadsorption Column, Cypress Bioscience, Inc., San Diego, CA, U.S.A.) in patients with refractory rheumatoid arthritis (RA). Eligibility criteria required adult RA patients who had failed either methotrexate or 2 other disease modifying antirheumatic drugs (DMARD) and who had predefined active disease. All disease-modifying agents were discontinued at least 30 days prior to entry. Patients received 12 weekly procedures after being randomized to the active treatment arm or to the sham treatment arm (apheresis only). Evaluations were double-blinded and occurred at baseline and periodically for 24 weeks thereafter. Primary efficacy was assessed at 7 and 8 weeks after the completion of 12 treatments (at trial Weeks 19 and 20) using the American College of Rheumatology (ACR) definition of improvement (1,2), and results from the assessments at Weeks 19 and 20 were averaged. Ninety-nine randomized patients had a mean disease duration of 15.4 years and received an average of greater than 5 DMARD regimens prior to entry. Analysis of patients who completed all treatments and follow-up indicated that 15 of 36 (41.7%) column-treated patients responded compared to 5 of 32 (15.6%) sham-treated patients (p < or = 0.003). Intent to treat analysis of all patients who were randomized in the study indicated 15 of 52 (28.9%) column-treated patients responded compared to only 5 of 47 (10.6%) patients who received sham treatments (p = .005). Common adverse events (AEs) included joint pain, fatigue, joint swelling, and hypotension. Central line usage was clearly associated with significant AEs during this trial and is not recommended. Hemoglobin, hematocrit, and mean corpuscular volume values decreased similarly in both treatment arms, attributed to phlebotomy for laboratory and scientific studies and to small, repetitive (normal) apheresis losses. Other AEs such as nausea, rash, pruritus, flushing, and fever occurred in 1 to 6% of treatments in each arm (NS). There was no significant increase in AEs in column-treated patients compared to sham-treated patients. Protein A immunoadsorption was proven to be a new therapeutic alternative in patients with severe, refractory disease.

Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, Smolen J, Emery P, Harriman G, Feldmann M, Lipsky P. · The Kennedy Institute of Rheumatology and The Imperial College School of Medicine at Charing Cross Hospital, London, UK. · Lancet. · Pubmed #10622295 No free full text.

Abstract: BACKGROUND: Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate, a standard treatment for this disease. There is evidence that antitumour necrosis factor alpha (TNFalpha) is efficacious in relief of signs and symptoms. We therefore investigated whether infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate. METHODS: In an international double-blind placebo-controlled phase III clinical trial, 428 patients who had active rheumatoid arthritis, who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks, were randomised to placebo (n=88) or one of four regimens of infliximab at weeks 0, 2, and 6. Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate (median 15 mg/week for > or =6 months, range 10-35 mg/wk). Patients were assessed every 4 weeks for 30 weeks. FINDINGS: At 30 weeks, the American College of Rheumatology (20) response criteria, representing a 20% improvement from baseline, were achieved in 53, 50, 58, and 52% of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks, respectively, compared with 20% of patients receiving placebo plus methotrexate (p<0.001 for each of the four infliximab regimens vs placebo). A 50% improvement was achieved in 29, 27, 26, and 31% of infliximab plus methotrexate in the same treatment groups, compared with 5% of patients on placebo plus methotrexate (p<0.001). Infliximab was well-tolerated; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group. INTERPRETATION: During 30 weeks, treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate.

Strand V, Cohen S, Schiff M, Weaver A, Fleischmann R, Cannon G, Fox R, Moreland L, Olsen N, Furst D, Caldwell J, Kaine J, Sharp J, Hurley F, Loew-Friedrich I. · Stanford University, Calif, USA. · Arch Intern Med. · Pubmed #10573044 links to  free full text

Abstract: CONTEXT: Leflunomide is a reversible inhibitor of de novo pyrimidine synthesis shown to be effective in a phase 2 trial in 402 patients with active rheumatoid arthritis (RA). OBJECTIVE: To compare the efficacy and safety of leflunomide treatment with placebo and methotrexate treatment in patients with active RA. DESIGN: Randomized, double-blind, placebo, and active-controlled 12-month study. SETTING: Forty-seven university and private rheumatology practices in the United States and Canada. PATIENTS: Diagnosis of RA by the American College of Rheumatology (ACR) criteria for duration of 6 months or longer and no previous methotrexate treatment. INTERVENTION: Leflunomide treatment (20 mg/d), placebo, or methotrexate treatment (7.5-15 mg/wk). MAIN OUTCOME MEASURES: American College of Rheumatology success rate (completed 52 weeks of treatment and met the ACR > or = 20% response criteria), disease progression as assessed by x-ray films, and improvement in function and health-related quality of life using the intent-to-treat population. RESULTS: The 482 patients studied were predominantly women (mean age, 54 years; mean disease duration, 6.7 years) for whom a mean of 0.8 disease-modifying antirheumatic drugs had failed. The ACR response and success rates for patients receiving leflunomide treatment (52% and 41%, respectively) and methotrexate treatment (46% and 35%, respectively) were significantly higher than those for patients receiving placebo (26% and 19%, respectively) (P<.001), and they were statistically equivalent, with mean time to initial response at 8.4 weeks for patients receiving leflunomide vs 9.5 weeks for patients receiving methotrexate therapy. X-ray analyses demonstrated less disease progression with leflunomide (P=.001) and methotrexate (P = .02) therapy than with placebo. Leflunomide and methotrexate treatment improved measures of physical function and health-related quality of life significantly more than placebo (P<.001 and P<.05, respectively). Common adverse events for patients receiving leflunomide treatment included gastrointestinal complaints, skin rash, and reversible alopecia. Asymptomatic transaminase elevations resulted in treatment discontinuations for 7.1% of patients receiving leflunomide therapy, 1.7% of patients receiving placebo, and 3.3% of patients receiving methotrexate therapy. CONCLUSIONS: Clinical responses following administration of leflunomide, a new therapeutic agent for the treatment of RA, were statistically superior to those with placebo and equivalent to those with methotrexate treatment. Both active treatments improved signs and symptoms of active RA, delayed disease progression as demonstrated by x-ray films, and improved function and health-related quality of life.

Caldwell J, Gendreau RM, Furst D, Wiesenhutter C, Quagliata F, Spindler J, Bertram J. · Virginia Mason Research Center, University of Washington, Seattle, USA. · J Rheumatol. · Pubmed #10451058 No free full text.

Abstract: OBJECTIVE: To assess the safety and effectiveness of extracorporeal treatments with protein A (Prosorba) columns in the treatment of patients with severe refractory rheumatoid arthritis (RA) in an open label pilot study. METHODS: Fifteen patients with RA who had failed to respond to 2 or more disease modifying antirheumatic drugs were "washed out" for 1-3 months before enrollment into this 6 month pilot study. The treatment schedule called for patients to receive apheresis treatments across staphylococcal protein A columns once a week for 12 weeks. Clinical evaluations of RA activity, defined by Paulus criteria, were conducted at study enrollment (baseline) and monthly throughout the treatment phase. In addition, examinations were conducted at 2, 4, 8, and 12 weeks after the last treatment. Fourteen patients received all 12 scheduled treatments, while one patient received only 10 treatments due to complications secondary to pneumonia. RESULTS: Using Paulus 50% criteria, 9 of 15 (60%) patients were improved at the 4th month, and one more fulfilled >20% Paulus criteria (7%) in the 5th month after starting therapy. The study group reported an average of 2.47 adverse effects per treatment, of which the most common were joint pain and swelling and fatigue of short duration (arthritic flare). CONCLUSION: The adverse effects associated with this apheresis based treatment proved to be manageable and of short duration and resolved without sequelae. The results suggest that extracorporeal protein A therapy may have a role in the management of refractory RA, and encouraged the initiation of a larger, blinded, controlled clinical trial.

Wolfe F, Michaud K, Pincus T, Furst D, Keystone E. · National Data Bank for Rheumatic Diseases, Wichita, Kansas 67214, USA. · Arthritis Rheum. · Pubmed #16320335 links to  free full text

Abstract: OBJECTIVE: The Disease Activity Score (DAS) is widely used in clinical trials. A DAS of 5.1 defines the level of severe rheumatoid arthritis (RA) and is the criterion for the initiation of anti-tumor necrosis factor therapy in the UK and The Netherlands. In North America, similar rules are sometimes imposed. However, it is not known how accurately the DAS characterizes RA activity. The present study was undertaken to determine the concordance between DAS scores and physicians' assessments of RA activity, to investigate factors relating to discrepancies, and to assess the suitability of using the DAS in individual patients. METHODS: Six hundred sixty-nine RA patients were assessed using the DAS and other clinical measures. A physician's global estimate of RA activity was performed using an 11-point predefined scale and a standard definition of disease activity. RESULTS: The DAS and physician global assessment had substantially different distributions of values. The level of agreement (Kendall's tau-a) between DAS scores and physician global assessments was 49% (95% confidence interval 45-53%), Lin's coefficient of concordance was 0.62, and the Bland-Altman 95% limits of agreement were -3.17 and 3.99. These results suggest poor-to-moderate concordance between the 2 measures of disease activity. CONCLUSION: The DAS and the physician's assessment of RA activity do not approach, value, and weight RA variables to the same extent, suggesting that RA activity is not evaluated similarly by North American physicians and with the DAS. The scales do not have acceptable levels of concordance. There is too much inherent variability in the DAS and other RA scales (e.g., the Health Assessment Questionnaire) to recommend them as sole determinants of RA activity for clinical or regulatory purposes.

Dervieux T, Furst D, Lein DO, Capps R, Smith K, Caldwell J, Kremer J. · Prometheus Laboratories, San Diego, CA, USA. · Ann Rheum Dis. · Pubmed #15677700 links to  free full text

Abstract: OBJECTIVE: To investigate the contribution of red blood cell (RBC) methotrexate polyglutamates (MTX PGs), RBC folate polyglutamates (folate PGs), and a pharmacogenetic index to the clinical status of patients with rheumatoid arthritis treated with MTX. METHODS: 226 adult patients treated with weekly MTX for more than 3 months were enrolled at three sites in a multicentred cross sectional observational study. Clinical status was assessed by the number of joint counts, physician's global assessment of disease activity, and a modified Health Assessment Questionnaire (mHAQ). RBC MTX PG and folate PG metabolite levels were measured by high performance liquid chromatography fluorometry and radioassay, respectively. A composite pharmacogenetic index comprising low penetrance genetic polymorphisms in reduced folate carrier (RFC-1 G80A), AICAR transformylase (ATIC C347G), and thymidylate synthase (TSER*2/*3) was calculated. Statistical analyses were by multivariate linear regression with clinical measures as dependent variables and metabolite levels and the pharmacogenetic index as independent variables after adjustment for other covariates. RESULTS: Multivariate analysis showed that lower RBC MTX PG levels (median 40 nmol/l) and a lower pharmacogenetic index (median 2) were associated with a higher number of joint counts, higher disease activity, and higher mHAQ (p<0.09). Multivariate analysis also established that higher RBC folate PG levels (median 1062 nmol/l) were associated with a higher number of tender and swollen joints after adjustment for RBC MTX PG levels and the pharmacogenetic index (p<0.05). CONCLUSION: Pharmacogenetic and metabolite measurements may be useful in optimising MTX treatment. Prospective studies are warranted to investigate the predictive value of these markers for MTX efficacy.

Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, Kremer J. · Prometheus Laboratories, San Diego, California, USA. · Arthritis Rheum. · Pubmed #15457444 links to  free full text

Abstract: OBJECTIVE: Methotrexate (MTX) enters cells through the reduced folate carrier (RFC-1) and exerts part of its effects through polyglutamation to MTX polyglutamates (MTXPGs) and inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) and thymidylate synthase (TS). We investigated the contribution of common genetic polymorphisms in RFC-1 (G80A), ATIC (C347G), and TS (28-bp tandem repeats located in the TS enhancer region [TSER*2/*3]) and of MTXPGs to the effect of MTX in patients with rheumatoid arthritis. METHODS: The study was cross-sectional. All patients received MTX for at least 3 months. The numbers of tender and swollen joints, the Visual Analog Scale (VAS) scores for the physician's global assessment of disease activity, and the modified Health Assessment Questionnaire scores were collected. Using the VAS score for the physician's assessment of patient's response to MTX, the population of patients was dichotomized into responders to MTX (VAS score < or =2 cm) and nonresponders to MTX (VAS score >2 cm). A pharmacogenetic index was calculated as the sum of homozygous variant genotypes (RFC-1 AA + ATIC 347GG + TSER *2/*2) carried by the patients. MTXPG concentrations were measured in red blood cells (RBCs) by high-performance liquid chromatography. RESULTS: The dose of MTX was not associated with the effects of MTX (P > 0.05). In contrast, increased RBC long-chain MTXPG concentrations (median 40 nmoles/liter; range <5-131 nmoles/liter) and an increased pharmacogenetic index were associated with a lower number of tender and swollen joints (P < 0.05) and a lower score for the physician's global assessment of disease activity (P < or = 0.001). Patients with RBC MTXPG levels of >60 nmoles/liter and carriers of a homozygous variant genotype were 14.0-fold (95% confidence interval [95% CI] 3.6-53.8) and 3.7-fold (95% CI 1.7-9.1), respectively, more likely to have a good response to MTX (P <or = 0.01). CONCLUSION: These data suggest that measuring RBC MTXPG levels and/or the common polymorphisms in the folate-purine-pyrimidine pathway may help in monitoring MTX therapy.