Recent Advances in the Treatment of SLE
Recent Advances in the Treatment of SLE
Antimalarials have been used in rheumatic diseases for many years. HCQ's immunomodulating properties were discovered after it was used as malaria prophylaxis in the 1950s. This drug acts on different pathways and has multiple mechanisms of action, including blockage of low-affinity antigens (such as self-antigens), alteration of intracellular pH, decrease in macrophage-mediated cytokine production, inhibition of phospholipase A2 and C, decrease of estrogen production, inhibition of platelet aggregation and adhesion, induction of apoptosis, antiproliferative effects and it can dissolve circulating immune complexes. Because the immune response against high-affinity antigens such as bacterial peptides is not impaired, the result is immunomodulation without immunosuppression. HCQ prevents and alleviates articular and skin flares, protects from UV light and is associated with a milder disease. It improves sicca syndrome and facilitates the response to MMF in patients with renal involvement. Among other benefits, HCQ can reduce total cholesterol, very low density lipoprotein cholesterol and triglyceride and increase high density lipoprotein cholesterol levels. By helping to control glycaemia it may also decrease the risk of diabetes. There are reports of an association with a reduction of up to 50% of the frequency of coronary heart disease and of the risk of development of carotid plaque, which makes it an especially good option for patients who are also treated with corticosteroids. It also has antithrombotic properties and some potential antineoplastic effects have been described.
Most importantly, HCQ prevents damage. In two studies in three ethnic groups, in the LUMINA cohort, HCQ use was associated with a longer time to integument damage over a mean disease duration of 5.9 ± 3.7 years (hazard ratio: 0.23; 95% CI: 0.12–0.47) and with a reduced risk of damage accrual de novo over a follow-up period of 5 years; other groups demonstrated the same benefit.
A systemic review on the clinical efficacy and safety of antimalarial therapy notes that disease activity was reduced in all studies in approximately 50% of the patients.
Probably as a result of all this, it reduces mortality. Both in the study by Ruiz-Irastorza et al. with a mostly Caucasian cohort, and in the LUMINA cohort, with an multiethnic group, HCQ was shown to have a protective effect on survival.
It should be stated that, regarding the overall efficacy of antimalarials, confounders cannot be excluded because these drugs are frequently used in milder cases and frequently discontinued in patients with severe disease.
The toxicity of antimalarials is mild and not common, with an even lower incidence in HCQ compared with chloroquine. The most frequently affected organs are the skin and gastrointestinal system.
Advances in the Use of Nonsteroidals/Immunosuppressives
Antimalarials have been used in rheumatic diseases for many years. HCQ's immunomodulating properties were discovered after it was used as malaria prophylaxis in the 1950s. This drug acts on different pathways and has multiple mechanisms of action, including blockage of low-affinity antigens (such as self-antigens), alteration of intracellular pH, decrease in macrophage-mediated cytokine production, inhibition of phospholipase A2 and C, decrease of estrogen production, inhibition of platelet aggregation and adhesion, induction of apoptosis, antiproliferative effects and it can dissolve circulating immune complexes. Because the immune response against high-affinity antigens such as bacterial peptides is not impaired, the result is immunomodulation without immunosuppression. HCQ prevents and alleviates articular and skin flares, protects from UV light and is associated with a milder disease. It improves sicca syndrome and facilitates the response to MMF in patients with renal involvement. Among other benefits, HCQ can reduce total cholesterol, very low density lipoprotein cholesterol and triglyceride and increase high density lipoprotein cholesterol levels. By helping to control glycaemia it may also decrease the risk of diabetes. There are reports of an association with a reduction of up to 50% of the frequency of coronary heart disease and of the risk of development of carotid plaque, which makes it an especially good option for patients who are also treated with corticosteroids. It also has antithrombotic properties and some potential antineoplastic effects have been described.
Most importantly, HCQ prevents damage. In two studies in three ethnic groups, in the LUMINA cohort, HCQ use was associated with a longer time to integument damage over a mean disease duration of 5.9 ± 3.7 years (hazard ratio: 0.23; 95% CI: 0.12–0.47) and with a reduced risk of damage accrual de novo over a follow-up period of 5 years; other groups demonstrated the same benefit.
A systemic review on the clinical efficacy and safety of antimalarial therapy notes that disease activity was reduced in all studies in approximately 50% of the patients.
Probably as a result of all this, it reduces mortality. Both in the study by Ruiz-Irastorza et al. with a mostly Caucasian cohort, and in the LUMINA cohort, with an multiethnic group, HCQ was shown to have a protective effect on survival.
It should be stated that, regarding the overall efficacy of antimalarials, confounders cannot be excluded because these drugs are frequently used in milder cases and frequently discontinued in patients with severe disease.
The toxicity of antimalarials is mild and not common, with an even lower incidence in HCQ compared with chloroquine. The most frequently affected organs are the skin and gastrointestinal system.
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