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Biochemical Indices Ofresponse to Hydroxychloroquine and Sodium Aurothiomalate in Rheumatoid Arthritis 481

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Biochemical Indices Ofresponse to Hydroxychloroquine and Sodium Aurothiomalate in Rheumatoid Arthritis 481 Ann Rheum Dis: first published as 10.1136/ard.40.5.480 on 1 October 1981. Downloaded from Annals of the Rheumatic Diseases, 1981, 40, 480-488 Biochemical indices of response to hydroxychloroquine and sodium aurothiomalate in rheumatoid arthritis J. S. DIXON, M. E. PICKUP, H. A. BIRD, M. R. LEE, V. WRIGHT, AND W. W. DOWNIE From the Clinical Pharmacology Unit, Royal Bath Hospital, Harrogate, and the University Department of Medicine, General Infirmary, Leeds SUMMARY Biochemical and clinical changes have been monitored in 30 patients with rheumatoid arthritis treated with either hydroxychloroquine or sodium aurothiomalate over a period of 6 months. Acute-phase reactants improved in both treatment groups, while serum sulphydryl and serum histidine improved only in the gold-treated patients. Correlation matrices were constructed from mean clinical and biochemical data at successive clinic visits. Correlations obtained with gold were more frequent and of a higher level of significance than those obtained with hydroxychloro- quine at the doses we studied. This lends support to the use of correlation matrices as a screening test for potential long-term antirheumatoid activity of drugs in man. copyright. In an attempt to define biochemical and clinical 39 to 66 years; 2 male, aged 31 and 49 years) were changes that occur when patients with rheumatoid allocated to HCQ therapy, and a further 15 patients arthritis are exposed for the first time to 'specific (11 female, mean age 52 7, range 36 to 67 years; antirheumatoid' therapy, and to see if these changes 4 male, mean age 54*5, range 45 to 64 years) were differ between drugs we have performed serial allocated to gold therapy. All patients had classical biochemical and clinical assessments over the first 6 or definite RA (American Rheumatism Association months of treatment with a series of drugs for which criteria) and at least moderate disease activity http://ard.bmj.com/ antirheumatoid action has been claimed. Our previously defined 12 by the presence of at least 3 of results for groups of 15 patients treated with D- the following 5 criteria: (a) tenderness of more than penicillamine' 2 and alclofenac2 have been described. 6 joints; (b) swelling of more than 3 joints; (c) morn- We have now added 2 further groups of patients ing stiffness longer than 45 minutes; (d) articular treated with hydroxychloroquine sulphate (HCQ) index more than 20; (e) ESR more than 28 mm. h-1. and sodium aurothiomalate (gold) in order to None of the patients had received specific anti- compare possible differences in biochemical response rheumatoid drug therapy (e.g., gold, penicillamine, and to consider whether any particular changes are HCQ) before the present study. Patient exclusions on September 27, 2021 by guest. Protected indicative of specific antirheumatoid effect. We were also as previously described.' 2 have previously suggested that comparison of cor- relation matrices, constructed between mean data DRUG DOSAGE for biochemical and clinical variables, has relevance Over a 24-week period HCQ was given in a dose of as a screening test for antirheumatoid activity.2 We 200 mg b.d. and gold in a dose of 50 mg.week- have therefore compared similar matrices for HCQ intramuscularly until lg had been given; then 50 mg. and gold. month-' irrespective of clinical response. Both groups received enteric coated aspirin in a Patients and methods dose of 3- 6g.day-' in the 2 weeks immediately preceding the study to establish 'baseline' conditions PATIENTS for clinical and systemic variables. During the 24 Fifteen patients (13 female, mean age 51-8, range weeks of the study patients took supplementary Accepted for publication 6 November 1980 enteric coated aspirin as required. However, 1 Correspondence to Professor V. Wright, Clinical Pharma- cology Unit, Royal Bath Hospital, Cornwall Road, Harrogate patient in each group took dextropropoxyphene and HGI 2PS. paracetamol tablets (Distalgesic) in place of aspirin 480 Ann Rheum Dis: first published as 10.1136/ard.40.5.480 on 1 October 1981. Downloaded from Biochemical indices ofresponse to hydroxychloroquine and sodium aurothiomalate in rheumatoid arthritis 481 HYDROXYCHLORNUINE GOLD cn cn X Ip Li (N z z - CSa -_ 0 CY CN ciCY a CL- CL Fi.- I. - 1r'- a- cl Li) Z- W z Ci C) Ci r (N- z ED copyright. U)f' CY. CN (N zaC14 http://ard.bmj.com/ W Ln _ - LiJ L C' GD- r ~C'P U (N C) LnU on September 27, 2021 by guest. Protected LiJ CL! Uci -I I L-i I - C.) r_ Li 6 12 16 20 2' T 8 E 1E2 16 20 2 TIME ILWEEKS1 T IME WEEKS) Fig. 1 Clinical data (mean±SE) for rheumatoidpatients treated with hydroxychloroquine (left) and sodium aurothiomalate (right). Changes in individualparameters reaching statistical significance (Wilcoxon rank sum test) when compared with data at week 0 are indicated by hatched (p<0-05) and closed (p<O.OJ) data points. Ann Rheum Dis: first published as 10.1136/ard.40.5.480 on 1 October 1981. Downloaded from 482 Dixon, Pickup, Bird, Lee, Wright, Downie HYDROXYCHLOROQUINE GOLD -CD c3 CD N- IJ J CD un C C Q~C'4 o EDCD CD C-) CD4 copyright. M>I CD zCD O _F CD a C) cI http://ard.bmj.com/ r'- C) - CD CD C-D on September 27, 2021 by guest. Protected - T i CY N-) I , I 0 W 8 12 16 20 24 0 8 12 16 20 2Y T IME (WEEKSI TI ME (WEEKS) 2A Figs. 2 A, B, C Biochemical data (mean +SE) for rheumatoid patients treated with hydroxychloroquine (left) and sodium aurothiomalate (right). Changes in individual parameters reaching statistical significance (Wilcoxon rank sum test) when compared with data at week 0 are indicated by hatched (p <0-05) and closed (p <0-01) data points. Ann Rheum Dis: first published as 10.1136/ard.40.5.480 on 1 October 1981. Downloaded from Biochemical indices ofresponse to hydroxychloroquine and sodium aurothiomalate in rheumatoid arthritis 483 HYDROXYCHLOROQUINE GOLD z Lii ID C-z C' a, LA. LA. CN I 0, GD a:, N. C) LD _u N.wC - N. z z copyright. u iD N-. CLN. a c,4 ol_ ED CY) http://ard.bmj.com/ .1- a,Co cn - j_ _naT) cr) C) CND Z r n CN dm onCV CV on September 27, 2021 by guest. Protected CV) I cn4 - IC' C..' - C:. a, - I I I I I 0 Y, 8 12 16 20 2Y, 0 Y- 8 1 2 1 6 20 2Y T IME (WEEKS1 TI MiE (WEEKS) 2B Ann Rheum Dis: first published as 10.1136/ard.40.5.480 on 1 October 1981. Downloaded from 484 Dixon, Pickup, Bird, Lee, Wright, Downiie HYDROXYCILOROQUINE GOLD C6- 0- (-A CD CD- ar. Q CD 0 - .- a'_ J- copyright. LU) Ca LCD 1r- 0(Y) CO cm In ^t9 CD (D- _A CC) a.CMC http://ard.bmj.com/ E_ 3 0 L3 -~ (Ea Q Xn LCDCD on September 27, 2021 by guest. Protected Ln -A (- CD4 CD4 CY 2:lfl lLn _4 tJ T L- U)-cn I Wr 8 12 16 20 2Y 0 8 1 2 1 6 20 2N TIMEfWEEKS1 T IME (WEEKS ) 2C Ann Rheum Dis: first published as 10.1136/ard.40.5.480 on 1 October 1981. Downloaded from Biochemical indices ofresponse to hydroxychloroquine and sodium aurothiomalate in rheumatoid arthritis 485 owing to aspirin intolerance. No other drugs were STATISTICAL METHODS allowed except prednisolone therapy in constant To test for significant changes in individual clinical dosage (maximum 7 5 mg.daily) for 2 patients in or laboratory variables over the 24-week treatment each drug group. period week 0 data were compared in turn with data from successive clinic visits by the Wilcoxon matched ASSESSMENT PROCEDURES pairs signed rank test for paired data.6 One-way Patients were seen at weeks -2, 0, 2, 4, 8, 12, 16, 20, analysis of variance was used to test for any dif- and 24 (0 = date of starting specific antirheumatoid ferences between week 0 data for each variable in the drug therapy). At each visit 18 biochemical and 8 2 drug groups. Correlation matrices were con- clinical assessments were made as previously structed between clinical and laboratory variables described.' 2 for both HCQ and gold in turn. Each laboratory In view of the reported retinopathy associated variable was correlated (Pearson correlation) in with chloroquine and HCQ therapy" routine turn with each clinical variable; mean data obtained ophthalmological tests were performed on the 15 from each of the 8 clinic visits from the start of HCQ-treated patients. specific therapy were used.2 All patients completed the 24-week treatment Results period, irrespective of clinical response, though 2 patients on hydroxychloroquine who failed to HYDROXYCHLOROQUINE THERAPY attend after week 4 were not replaced. Of the 13 patients completing 24 weeks' treatment Table 1 Correlation matrices for (A) hydroxychloroquine and (B) sodium aurothiomalate. Figures shown represent the significance (p<) ofPearson correlations (r) between mean clinical and mean biochemical variables at successive clinic visits (n=8). Biochemical variables are arranged so that those showing highly significant correlations with clinical variables are placed towards the top Articular Joint size Summated Aspirin Early Grip Pain score Functional copyright. index change dose morning strength grade score stiffness A. Hydroxychloroquine CRP 0.01 0.01 0.001 - - - 0.01 0-05 Alkaline phosphatase 0.05 0.01 0-05 0.001 0.01 - - - Plasma viscosity 0 01 0-001 0.001 - - - 0°05 ESR 0-01 0-05 - - - - 0-05 - Albumin 0.05 0-01 0.05 - 0.05 - - Haptoglobin 0-05 0-01 0.01 - - - 0.05 GGTP - - 0*05 - - 005 0.05 - http://ard.bmj.com/ WBC - 0-05 0-05 - - - - - Fibrinogen - 0-05 0-01 - - SGOT - -- - 0.05 - _ Platelet count - - - - 0.05 Bilirubin - - - - - - - - Creatinine - - -- - - - - Globulin - - - - - - - - Protein - - - - - - - - Sulphydryl - - - - - - - - Histidine - - - - - - - - on September 27, 2021 by guest.
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