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PubMed1983

Risk/benefit analysis of hydroxychloroquine sulfate treatment in rheumatoid arthritis.

Controlled studies have their limitations in assessing the clinical effectiveness of drugs, particularly in patients requiring years of treatment. Retrospective analysis of long-term therapy can be useful and can be summarized easily by life-table analysis. Our first analysis revealed that side effects were more common in patients treated with gold than in those receiving hydroxychloroquine sulfate. Relapses in patients who were treated with gold occurred at a continuous rate over time, whereas in patients treated with hydroxychloroquine this rate leveled off after 20 months of treatment. Our second analysis revealed that the rate of drug discontinuation was lowest with hydroxychloroquine, followed--in order of discontinuation--by gold, D-penicillamine, and levamisole. In both studies, no definite retinopathy was seen in any patient. Since hydroxychloroquine is better tolerated and easier to use than D-penicillamine, gold, or levamisole, it is a reasonable choice for the first trial of a slow-acting antirheumatic drug.

Actuarial Analysis↗
PubMed1987

Hydroxychloroquine treatment of hypercalcemia in a patient with sarcoidosis undergoing hemodialysis.

Hypercalcemia developed in a patient undergoing long-term hemodialysis, and she was found to have noncaseating granulomas on lymph node biopsy. Hydroxychloroquine was administered as therapy for the hypercalcemia. Over 24 weeks of treatment with the drug, concentrations of calcium and 1,25-dihydroxyvitamin D returned to normal. The results demonstrate the capacity of hydroxychloroquine to inhibit the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, and emphasize the efficacy of hydroxychloroquine as an alternate to corticosteroids in the treatment of hypercalcemia of granulomatous disease. Hydroxychloroquine may be preferred when existing skeletal disease, or a predisposition to osteopenia, provides relative contraindications to corticosteroid therapy.

Female↗
PubMed1989

Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis.

The effects of hydroxychloroquine and sulphasalazine on progression of joint damage shown by X-rays were compared in a double-blind, randomised trial in 60 patients with rheumatoid arthritis not previously treated with slow-acting antirheumatic drugs. X-rays of the hands and feet at the start and after 24 and 48 weeks of treatment were available for 28 patients treated with hydroxychloroquine and 22 treated with sulphasalazine. Erosions and joint space narrowing were scored by a single observer unaware of treatment. At baseline there were no significant differences in demographic, clinical, or radiographic characteristics between the treatment groups. Patients withdrawn because of lack of effect were included in the analysis. The median number of erosions was lower in the sulphasalazine than the hydroxychloroquine group at 24 weeks of treatment (2.5 vs 10) and the difference was significant at 48 weeks (5 vs 16; p less than 0.02). The difference in median total score of joint damage was significant at 24 weeks (6.5 vs 17; p less than 0.02) and at 48 weeks (8 vs 33; p less than 0.02). The increase in number of erosions and total score was significantly greater in the hydroxychloroquine than the sulphasalazine group, both after 24 weeks and after 48 weeks of treatment.

Adult↗
PubMed2002

Hydroxychloroquine ototoxicity in a child with idiopathic pulmonary haemosiderosis.

Hydroxychloroquine, a quinoline compound, rarely causes ototoxicity. According to the few reports in existence, hydroxychloroquine-induced ototoxicity occurred following prolonged therapy in adult patients with rheumatoid arthritis and lupus erythematosus. We report a case of unilateral sensorineural hearing loss in a 7-year-old girl with idiopathic pulmonary haemosiderosis, after 2 years of hydroxychloroquine treatment. Sensorineural hearing loss has previously been reported with hydroxychloroquine treatment, but this is the first report in a child and associated to idiopathic pulmonary haemosiderosis and has the characteristic of being unilateral.

Acoustic Impedance Tests↗
PubMed1984

Cutaneous lesions of dermatomyositis are improved by hydroxychloroquine.

Dermatomyositis (DM) is a collagen vascular disease with prominent cutaneous findings. Although the myositis often responds to therapy with corticosteroids and/or immunosuppressives, the cutaneous disease may not respond. Seven patients with cutaneous lesions of DM that had not responded to therapy were treated with hydroxychloroquine in an open study. Three patients had idiopathic DM, one had DM without myositis, one had DM with malignancy, and one had adolescent DM. The response to the addition of hydroxychloroquine was good in all of the patients, and three had total resolution of their skin lesions. In two patients the corticosteroid dosage could be tapered. Therapy with hydroxychloroquine did not appear to have any beneficial effect on the myositis. We conclude that hydroxychloroquine may have a role as an adjuvant to the therapy of patients with cutaneous lesions of DM.

Adenocarcinoma↗
PubMed2001

Treatment of hydroxychloroquine overdose.

Hydroxychloroquine overdoses are rarely reported with 7 previous cases found in the English medical literature. We report a case and review the literature. A 16-year-old girl ingested a handful of hydroxychloroquine 200mg, 30 minutes before presentation and presented with tachycardia (heart rate 110 beats/min), hypotension (systolic blood pressure 63 mm Hg), central nervous system depression, conduction defects (QRS = 0.14 msec), and hypokalemia (K = 2.1 meq/L). She was treated with fluid boluses and dopamine, oxygen, and potassium supplementation. Toxicologic tests confirmed the presence of hydroxychloroquine. The patient's hypotension resolved within 4.5 hours, serum potassium stabilized in 24 hours, and tachycardia gradually decreased over 3 days. Although hydroxychloroquine overdoses are very rare, life-threatening hypotension, conduction problems, and hypokalemia can occur within 30 minutes of ingestion. Symptoms are similar to chloroquine and treatment must be implemented quickly and should be modeled after experience with chloroquine overdoses. Treatment modalities need further study, but current recommendations are: (1) diazepam for seizures and sedation; (2) early intubation and mechanical ventilation; (3) epinephrine for treatment of vasodilation and myocardial depression; (4) potassium replacement with close monitoring of levels; (5) charcoal for gastrointestinal decontamination if ingestion occurred within an hour; (6) high dose diazepam for life-threatening symptoms, until more information becomes available. No value was found for serum alkalinization or extracorporeal methods of drug removal.

Adolescent↗
PubMed1986

Penicillamine and hydroxychloroquine in the treatment of severe juvenile rheumatoid arthritis. Results of the U.S.A.-U.S.S.R. double-blind placebo-controlled trial.

One hundred sixty-two children with severe juvenile rheumatoid arthritis were entered in a randomized, double-blind, placebo-controlled 12-month clinical trial designed to establish the efficacy and safety of two slower-acting antirheumatic drugs, penicillamine and hydroxychloroquine. The study was a cooperative effort of the United States and the Soviet Union. One group of subjects received 10 mg of penicillamine per kilogram of body weight per day, another group received 6 mg of hydroxychloroquine per kilogram daily, and a third group received placebo. All three groups were allowed a single concurrent nonsteroidal antiinflammatory drug, but no other antirheumatic medications, including corticosteroids. All three groups had dramatic improvement in many of the clinical and laboratory outcome variables after one year of study. There were no significant differences in efficacy between the penicillamine and placebo groups. Pain on movement was the only index of articular disease that was alleviated more by hydroxychloroquine than by placebo. Serious adverse drug reactions attributable to the active agents were rare. We were unable to demonstrate that, in the presence of a nonsteroidal antiinflammatory drug, either penicillamine or hydroxychloroquine is superior to placebo in the treatment of children with juvenile rheumatoid arthritis.

Administration, Oral↗
PubMed1996

Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications.

BACKGROUND: Rheumatoid arthritis is a common disease that causes substantial morbidity and mortality. The responses of patients with rheumatoid arthritis to treatment with a single so-called disease-modifying drug, such as methotrexate, are often suboptimal. Despite limited data, many patients are treated with combinations of these drugs. METHODS: We enrolled 102 patients with rheumatoid arthritis and poor responses to at least one disease-modifying drug in a two-year, double-blind, randomized study of treatment with methotrexate alone (7.5 to 17.5 mg per week), the combination of sulfasalazine (500 mg twice daily) and hydroxychloroquine (200 mg twice daily), or all three drugs. The dose of methotrexate was adjusted in an attempt to achieve remission in all patients. The primary and point of the study was the successful completion of two years of treatment with 50 percent improvement in composite symptoms of arthritis and no evidence of drug toxicity. RESULTS: Fifty of the 102 patients had 50 percent improvement at nine months and maintained at least that degree of improvement for two years without evidence of major drug toxicity. Among them were 24 of 31 patients treated with all three drugs (77 percent), 12 of 36 patients treated with methotrexate alone (33 percent, P < 0.001 for the comparison with the three-drug group), and 14 of 35 patients treated with sulfasalazine and hydroxychloroquine (40 percent), P = 0.003 for the comparison with the three-drug group). Seven patients in the methotrexate group and three patients in each of the other two groups discontinued treatment because of drug toxicity. CONCLUSIONS: In patients with rheumatoid arthritis, combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine is more effective than either methotrexate alone or a combination of sulfasalazine, and hydroxychloroquine.

Adult↗
PubMedDate not supplied

Aurothiomalate and hydroxychloroquine inhibit nitric oxide production in chondrocytes and in human osteoarthritic cartilage.

OBJECTIVES: Nitric oxide (NO) is a destructive mediator produced by activated chondrocytes. The aim of the present study was to investigate the effect of disease-modifying anti-rheumatic drugs (DMARDs) on interleukin-1beta (IL-1beta)-induced NO production in chondrocyte cultures, and in human osteoarthritic cartilage. RESULTS: Aurothiomalate, hydroxychloroquine, methotrexate and leflunomide inhibited IL-1beta-induced inducible NO synthase (iNOS) expression and NO production in immortalized H4 chondrocytes, while penicillamine and sulfasalazine had no effect. This can be explained by the fact that the four effective DMARDs also suppressed IL-1beta-induced activation of nuclear factor kappa B (NF-kappaB), which is a crucial transcription factor for iNOS. Aurothiomalate and hydroxychloroquine also inhibited IL-1beta-induced NO production in OA cartilage whereas methotrexate and leflunomide had no effect. CONCLUSION: Aurothiomalate and hydroxychloroquine suppressed IL-1beta-induced NO production in chondrocyte cultures and in OA cartilage. The results suggest an additional anti-inflammatory mechanism for aurothiomalate and hydroxychloroquine and indicates their possible therapeutic value in the treatment of osteoarthritis (OA).

Analysis of Variance↗
PubMed1987

The prescribing of chloroquine and hydroxychloroquine by consultant rheumatologists in the UK.

A questionnaire on chloroquine and hydroxychloroquine prescribing was circulated nationally to 212 consultant rheumatologists and 119 replies were analysed. Of all patients receiving second-line drugs, 10% were prescribed antimalarials, with hydroxychloroquine being used four times more frequently than chloroquine. Eighty-five per cent of rheumatologists always used the same dose of hydroxychloroquine or chloroquine. Only 5% considered patient's weight in deciding the dose. Fear of ocular toxicity was expressed by many physicians; 54% had experienced corneal deposits; 4% retinopathy and 40% believed cumulative dose determined toxicity. Much confusion existed over the necessity for and frequency of ophthalmological monitoring. Only 56% requested ophthalmological tests before commencing treatment, although 86% monitored the eyes during therapy. Other side-effects were believed to affect 1-10% of patients, with no anticipated difference between doses of 250 mg chloroquine and 400 mg hydroxychloroquine daily.

Arthritis, Rheumatoid↗
PubMed2004

Hydroxychloroquine therapy in patients with primary Sjögren's syndrome may improve salivary gland hypofunction by inhibition of glandular cholinesterase.

OBJECTIVE: To determine whether (i) cholinesterase activity is increased in the saliva of patients with primary Sjogren's syndrome (pSS), (ii) increased levels of cholinesterase of lymphocyte origin could interfere with the secretory activity of submandibular acinar cells, and (iii) hydroxychloroquine at therapeutic doses could interfere with cholinesterase activity. METHODS: The Ellman method was used to determine the levels of salivary cholinesterase activity and the K(i) of both chloroquine and hydroxychloroquine for serum cholinesterase. The ability of lymphocyte cholinesterase to inhibit the acetylcholine (ACh)-evoked rise in [Ca(2+)](i) in mouse submandibular acinar cells was determined using fura-2 microfluorimetry. RESULTS: Patients with pSS had significantly higher levels of cholinesterase activity in both their unstimulated (P < 0.05) and stimulated saliva (P < 0.0001) compared with control subjects. Lymphocyte cholinesterase was capable of inhibiting the ACh-evoked rise in [Ca(2+)](i). The in vitro K(i) for hydroxychloroquine inhibition of cholinesterase was 0.38 +/- 1.4 microM. CONCLUSION: These data suggest that increased levels of cholinesterase present in the salivary glands of patients with pSS may contribute to glandular hypofunction and provide evidence that the therapeutic enhancement of salivary secretion in patients with pSS by hydroxychloroquine may be mediated by inhibition of glandular cholinesterase activity, although further in vivo investigation is needed.

Animals↗
PubMedDate not supplied

Pilot tolerability studies of hydroxychloroquine and colchicine in Alzheimer disease.

Anti-inflammatory drugs may be useful in the treatment of Alzheimer disease (AD). In preparation for therapeutic trials, we conducted pilot feasibility studies of hydroxychloroquine alone and in combination with colchicine in subjects with AD. A total of 20 subjects with probable AD were treated with hydroxychloroquine 200 mg twice daily for 11 weeks, or hydroxychloroquine 200 mg twice daily plus colchicine 0.6 mg twice daily for 12 weeks; subjects were monitored for adverse medical, cognitive, or behavioral effects. Neither regimen caused adverse effects on cognitive or behavioral assessment scores. There were no significant side effects in subjects receiving hydroxychloroquine alone; 2 subjects receiving the two drugs together experienced diarrhea. We conclude that these regimens of anti-inflammatory therapy are well tolerated in subjects with AD, indicating the feasibility of large-scale therapeutic trials of these agents.

Aged↗
PubMed2003

Multifocal electroretinography evaluation for early detection of retinal dysfunction in patients taking hydroxychloroquine.

PURPOSE: To evaluate macular function using multifocal electroretinography (mfERG) in a cohort of asymptomatic patients taking hydroxychloroquine and a patient with maculopathy secondary to hydroxychloroquine treatment. METHODS: mfERG recordings were obtained for both eyes of 11 patients taking hydroxychloroquine without clinical signs of toxicity and 1 patient with toxic maculopathy. Initially, the classic m-sequence paradigm for the first-order kernel (103 hexagons; 2.7 candela x seconds/m2 peak luminance) was recorded. After that, another special stimulation mode was applied, which emphasized second-order adaptational effects (modulated multifocal flashes with interleaved global flashes, MF0F0 paradigm). RESULTS: The patient with toxic maculopathy and one patient without toxicity had multiple areas of decreased retinal responses bilaterally (classic m-sequence). The patient with toxicity and another three patients without toxicity presented with multiple areas of decreased retinal function in both eyes with the second-order component of the MF0F0 paradigm. Repeated recordings of 1 patient 8 months after the initial recording demonstrated evidence for reproducibility of the second-order adaptive effects. CONCLUSION: Clinically asymptomatic patients receiving hydroxychloroquine treatment can have substantial local decreases in their retinal function, as reflected by the changes in mfERG recordings, possibly indicating a preclinical stage of drug-related toxicity.

Adult↗
PubMed1997

Hydroxychloroquine and visual screening in a rheumatology outpatient clinic.

OBJECTIVE: To review 10 years' data relating to visual screening of patients taking hydroxychloroquine. METHODS: Following baseline visual assessment, ophthalmic monitoring was carried out at six monthly intervals on 758 patients while on hydroxychloroquine. This consisted of corrected visual acuity, central field screening with a red Amsler grid, slit lamp examination, and retinoscopy. RESULTS: None of the patients suffered visual impairment from retinal toxicity, though 12 reported visual disturbance. This was related to ocular muscle imbalance in four. In the remainder, none of the ocular findings was directly attributable to hydroxychloroquine. Ten patients reported defects when tested with a red Amsler grid. None was related to retinal toxicity. Seven patients developed corneal drug deposits which cleared on stopping or reducing the dose of hydroxy-chloroquine. CONCLUSIONS: The findings support the view that following baseline ophthalmic examination for patients receiving hydroxychloroquine, regular ophthalmic screening is not required if the daily dose is less than 6.5 mg kg-1 and the cumulative dose is less than 200 g.

Adolescent↗
PubMed1999

Inability of short-term, low-dose hydroxychloroquine to resolve vitamin D-mediated hypercalcemia in patients with B-cell lymphoma.

The 4-aminoquinolines, including chloroquine and hydroxychloroquine, have been successfully employed to treat patients with granuloma-forming disease-associated, vitamin D metabolite-mediated hypercalcemia. The calcium-lowering efficacy of these drugs has not been prospectively evaluated in patients with lymphoma and elevated 1,25-(OH)2D levels. Four such hypercalcemic patients with stage IV B-cell lymphoma were treated, two each, with either 400 mg daily oral hydroxychloroquine or a single course of prednisone-containing antitumor chemotherapy (CHOP). Antitumor therapy normalized the serum calcium and 1,25-(OH)2D concentration within 5 days. Over a 15-day period, hydroxychloroquine failed to reduce either the serum calcium or 1,25-(OH)2D level in lymphoma patients. In contrast, within 5 days 400 mg of hydroxychloroquine daily lowered elevated levels of calcium and 1,25-(OH)2D by 37% and 72%, respectively, in a hypercalcemic patient with sarcoidosis. These data suggest that regulation of the vitamin D-1-hydroxylase in lymphoma cells, the putative source of hormone in lymphoma patients, is refractory to the inhibitory actions of the aminoquinolines and that glucocorticoid-containing antitumor regimens are the antihypercalcemic therapies of choice in lymphoma patients with high 1,25-(OH)2D levels.

Adult↗
PubMed1985

Hydroxychloroquine treatment and the eye.

The eyes of 63 patients, age range 28 to 79 years, affected by rheumatoid arthritis and undergoing long-term hydroxychloroquine treatment were followed from 3 to 95 months. The daily dose of hydroxychloroquine was 300 mg, and after 5 months there was a pause of one month in the treatment. The total amount of hydroxychloroquine received ranged between 27 and 630 g. In the eye examination only one patient had corneal changes, and another patient had suspected retinal damage. This is in agreement with earlier studies. Hydroxychloroquine seems to be a safe alternative among the antimalarial drugs as far as eyes are concerned.

Adult↗
PubMed1999

Hydroxychloroquine in light eruption: new indication. Can be tried.

(1) Hydroxychloroquine sulphate is now approved for the prevention of light eruption. (2) The clinical file on benign summer light eruption is limited to a placebo-controlled trial showing that hydroxychloroquine does not reduce the frequency of eruptions after sunlight exposure. In contrast, it does seem to reduce the severity of these reactions, even though the effect is impossible to quantify. (3) The preventive efficacy of hydroxychloroquine in polymorphous light eruption has been demonstrated in a placebo-controlled trial showing a reduction in eruption but not in the accompanying pruritus. (4) Short treatment courses with hydroxychloroquine seem to be well tolerated. The danger of ocular lesions appears to be minimal.

Clinical Trials as Topic↗
PubMed1995

Hydroxychloroquine in the treatment of erosive osteoarthritis.

OBJECTIVE: Hydroxychloroquine has been used successfully in the treatment of inflammatory arthritides such as rheumatoid arthritis and systemic lupus erythematosus, and less commonly in the seronegative spondyloarthropathies. Our objective was to determine the effectiveness of hydroxy-chloroquine in inflammatory or erosive osteoarthritis (OA). METHODS: We retrospectively reviewed clinical records of 8 patients prescribed hydroxychloroquine therapy whose symptoms of erosive OA were unresponsive to nonsteroidal antiinflammatory drugs (NSAID). RESULTS: Hydroxychloroquine was effective in 6 of the 8 patients treated; it was well tolerated by all patients. CONCLUSION: The use of hydroxychloroquine in patients with erosive OA unresponsive to NSAID appears promising. Prospective studies are needed to confirm our observations.

Antirheumatic Agents↗