Lack of correlation between blood gold concentrations and clinical response in patients with definite or classic rheumatoid arthritis receiving auranofin or gold sodium thiomalate

Dahl, Stephen L.; Coleman, Miki L.; Williams, H. James; Altz‐Smith, Mary; Kay, Donald R.; Paulus, Harold E.; Weinstein, Arthur; Kaplan, Stanley B.

doi:10.1002/art.1780281104

Cited by 31 publications

(2 citation statements)

References 17 publications

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“…From these studies, it was not possible to define a therapeutic range or therapeutic threshold for QCQ. Althpugh this is disappointing, it is not a surprise, as several investigators have failed to demonstrate a relationship between blood levels of gold compounds or penicillamine and response in RA (10)(11)(12). Our results 'are consistent with those of Wollheim and coworkers, who found no relationship BRIEF REPORTS between increased CQ levels and therapeutic response (6).…”

Section: Global Evaluationmentioning

confidence: 99%

Plasma hydroxychloroquine concentrations and efficacy in rheumatoid arthritis

Miller

Fiechtner

Carpenter

et al. 1987

Arthritis & Rheumatism

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Plasma levels of hydroxychloroquine (HCQ) and its metabolites were measured, by high performance liquid chromatography, in 37 rheumatoid arthritis patients who could be clearly distinguished As responders (n = 28) or nonresponders (n = 9) to HCQ, 400 mglday. Efficacy in both groups was determined by the patients' erythrocyte sedimentation rates, joint counts, morning stiffness, globai assessments, Concurrent drug therapies, and grip strength. The response rate was 76%. Responders had a mean HCQ level of 213 ng/ml, versus 306 in nonresponders (P < 0.05). The mean level of HCQ plus total metabolites in respohders +as 363 ng/ml, versus 554 in nonresponders,(P < O.bI). We conclude that monitoring plasma kCQ levels is unlikely to be helpful in individualizing eeective drug dosage.The 4-aminoquinoline (4-AQ) compounds, chloroquine (CQ) and hydrox ychloroquine (HCQ), were introduced as aiitimalarials in 1943 have been used as antirheumatic compounds since 1951 (1). Their wide use has been inhibited by concern about irreversible ocular toxicity, which sometimes occurs. Many rheumatologists now believe that limitation of daily dosage and regular monitofing can prevent serious ocular hazards (1-4).By relating dosage to body weight, MacKenzie and Scherbel have estimated that 4.0 mg/kg/day of CQ or 6.4 mglkglday of HCQ offers high safety, while 5.4 mg/kg and 7.8 mg/kg cross the threshold into the toxic range (1). Even a dosage standardized for body weight, however, results in large inter-individual variation in blood levels of 4-AQ compounds. For example, a 5 mg/kg dosage of HCQ resulted in blood levels that ranged tenfold, from 0.1-1.0 pg/ml, in a pediatric population (4). For many drugs, clinical effects correlate better with blood concentration than With dosage (5); therefore, several researchers have attempted to correlate 4-AQ levels with their effects.Frisk-Holmberg and coworkers (3) found a strong correlation between serum concentration of CQ and incidence of all side effects. A safe concentration was 0.4 pg/ml, below which no side effects were observed. At concentrations >0.8 pg/ml, the incidence of side effects was 89%. Laaksonen et a1 (4) found that toxicity of any kind was rare in children who had serum concentrations of CQ <0.28 p g h l or HCQ CO.47 pg/ml. Wollheim and colleagues, however, found no correlation between therapeutic response and serum concentration of CQ in 15 rheumatoid arthritis (RA) patients after 3 months of treatment (6).Tht: above data thus suggest that monitoring of serum concentrations of the 4-AQ drugs may be helpful to avoid side effects, but not as an indicator of

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Section: Global Evaluationmentioning

confidence: 99%

Plasma hydroxychloroquine concentrations and efficacy in rheumatoid arthritis

Miller

Fiechtner

Carpenter

et al. 1987

Arthritis & Rheumatism

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“…They suggested significant clinical benefits in the patients receiving the adjusted dose compared with the fixed dose group. In contrast, Dahl et al (1985), who gave adult rheumatoid arthritis patients auranofin 3mg twice daily and sodium aurothiomalate IOmg in the first week, 25mg in the second week and 50mg weekly for 19 weeks, did not find a meaningful relationship between serum gold concentrations (0.8 to 0.9 mg/L after auranofin and 1 to 4 mg/L after sodium aurothiomalate) and efficacy. No such evaluation has been conducted in children.…”

Section: Goldmentioning

confidence: 82%

Clinical Pharmacokinetics of Drugs Used in Juvenile Arthritis

Skeith

Jamali

1991

Clinical Pharmacokinetics

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Juvenile arthritis is defined as the occurrence of objective evidence of arthritis for a minimum of 6 weeks, in a child 16 years of age or younger. With a reported incidence of 9 to 19.6 per 100,000 children, juvenile arthritis is considered to be a rare disease. There is no known cure; however, up to 75% of patients will undergo remission by late adolescence. Drugs used in the treatment of juvenile arthritis are divided into 2 major classes: (a) the nonsteroidal anti-inflammatory drugs (NSAIDs) including salicylates, naproxen, ibuprofen, fenoprofen, ketoprofen, flurbiprofen, indomethacin, sulindac, tolmetin and diclofenac, and (b) disease modifying agents which encompass drugs such as antimalarial agents, gold, methotrexate, penicillamine and sulfasalazine. In almost all the reports dealing with the pharmacokinetics of NSAIDs, the level of disease activity has not been noted. The level of activity is important since, during a flare, the plasma albumin may fall to the point that it causes a substantial and clinically significant increase in the unbound serum concentration of highly bound drugs. The relationship between the concentration of these drugs in the systemic circulation and their efficacy is not clear. However, for many of them, therapeutic drug monitoring is recommended as a means of reducing the possibility of toxic reactions. Further pharmacokinetic and -dynamic evaluations are needed for many of these drugs in juvenile arthritis.

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Treatment of rheumatoid arthritis

Weinblatt

Maier

1989

Arthritis & Rheumatism

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The management of the rheumatoid patient involves the considered use of pharmacologic agents as therapies to induce symptomatic relief and to reduce disease activity. Aspirin and nonsteroidal antiinflammatory drugs are used initially to lessen the degree of pain and swelling associated with the inflammatory disease process. The aggressive institution of second‐line therapy, previously known as disease‐modifying antiinflammatory rheumatic drugs, is advocated to modify the disease course itself. These second‐line treatments include antimalarials, gold salts, methotrexate, d‐penicillamine, and azathioprine. Randomized placebo controlled trials have demonstrated the efficacy of these compounds in this illness. Improvement in standard parameters of disease activity (number of painful and swollen joints, duration of morning stiffness, erythrocyte sedimentation rate) can be related to the therapeutic value of second‐line agents. Whether they modify radiographic progression is under rigorous study. Newer therapies under research investigation include sulfasalazine, cyclosporin A, and combination therapy.

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Lack of correlation between blood gold concentrations and clinical response in patients with definite or classic rheumatoid arthritis receiving auranofin or gold sodium thiomalate

Cited by 31 publications

References 17 publications

Plasma hydroxychloroquine concentrations and efficacy in rheumatoid arthritis

Plasma hydroxychloroquine concentrations and efficacy in rheumatoid arthritis

Clinical Pharmacokinetics of Drugs Used in Juvenile Arthritis

Treatment of rheumatoid arthritis

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