Showing posts with label Sjogren's Syndrome. Show all posts
Showing posts with label Sjogren's Syndrome. Show all posts

Friday, December 23, 2016

Risk Reduction of Retinopathy in the Therapy with Chloroquine and Hydroxychloroquine in Rheumatology




Chloroquine (CQ) has been developed for the therapy of malaria. It’s an old drug as the substance had already been discovered in 1934. You might know hydroxychloroquine (HCQ) Plaquenil or Quensyl, which differs from chloroquine just by the presence of a hydroxyl group. We use these antimalarials in rheumatology as DMARD (Disease Modifying Anti Rheumatic Drugs) to treat rheumatoid arthritis (often in combination with methotrexate), systemic lupus erythematodes (SLE), Sjoegren’s syndrome, and others. A study in 1985 found a lower rate of retinopathy in hydroxychloroquine when compared to chloroquine. As retinopathy is not reversible and as there is no present therapy, we need to reduce the risk for the development of antimalarial associated retinopathy.

In June 2016 the American Academy of Ophthalmology published recommendations on screening for chloroquine and hydroxychloroquine retinopathy. They recommend a maximum daily HCQ use of ≤5.0 mg/kg real weight. “The risk of toxicity is dependent on daily dose and duration of use. At recommended doses, the risk of toxicity up to 5 years is under 1% and up to 10 years is under 2%, but it rises to almost 20% after 20 years.” Higher dosage means higher risk, so we have to keep the daily dosage down. Long duration of therapy with antimalarials is another significant risk factor, so we must try to reduce the duration of this therapy. This might be hard to achieve in lupus. Renal disease is another risk factor to look for, but rheumatologists usually screen their patients for renal disease. And we have to look for tamoxifen, as this drug increases the risk for chloroquine and hydroxychloroquine retinopathy. This is sad to hear as the group of patients needing tamoxifen is also the group, where other therapy options like biologicals are contraindicated.

Risk Reduction of Retinopathy:
·         adapted dosage of CQ and HCQ
·         avoiding long duration of therapy
·         screening for renal disease
·         monitoring concomitant medication
·         screening for retinopathy

Links:

Wednesday, December 21, 2016

Iguratimod – new developments




You might have noticed, that I’ve been following the development of iguratimod very closely since 2012. Iguratimod is a disease modifying anti-rheumatic drug (DMARD); chemical formula: N-(3-Formamido-4-oxo-6-phenoxy-4H-chromen-7-yl)-methanesulfonamide. “Iguratimod is characterized by inhibitory effects on immunoglobulin production in B cells as well as inhibiting cytokine production. Its' mode of action comes by suppression of nuclear factor kappa B (NF-kB) activation.” It is approved for the treatment of rheumatoid arthritis in Japan as well as in China!

Rong Mu and colleagues presented the following study at the 2016 ACR Annual Meeting [#1622]: “Safety and Efficacy of Iguratimod in Patients with Active Rheumatoid Arthritis: A Multicenter, Single-Arm, Open-Label, Real World Study”. Conclusion: “Iguratimod was effective and well tolerated in active RA patients in this large sample phase IV clinical trial. No unexpected adverse drug reaction was found.” And let me add, I would have been surprised if this study showed any new data. But it confirms data from underpowered earlier studies. “1759 patients were enrolled in this study, among them 1751 were included in safety analysis, and 1597 patients were evaluated for efficacy.” 164 missing patients! That’s about 10%.

A second study by Lingshu Zhang and colleagues is about Sjoegren’s syndrome [#2666]: “Therapeutic Efficacy of Iguratimod in Patients with Primary Sjogren’s Syndrome”. Conclusion: “In subjects with pSS, IGU treatment resulted in clinically meaningful improvements in disease activity compared with conventional therapy. IGU affected B cell frequency and functions in pSS via inhibition of BAFF-R expression on B cells and inhibition of B cell antibody production.” The data supports the conclusion. I stumbled about the word meaningful, but as the ESSPRI is a patient reported index, I can live with the wording.

I see a potential for this drug on the world market, but I don’t see any commitment by the producers Eisai and Toyama Chemical to come to the international markets outside of East Asia.


Links:


Mu R. Safety and Efficacy of Iguratimod in Patients with Active Rheumatoid Arthritis: A Multicenter, Single-Arm, Open-Label, Real World Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/safety-and-efficacy-of-iguratimod-in-patients-with-active-rheumatoid-arthritis-a-multicenter-single-arm-open-label-real-world-study/. Accessed December 21, 2016.

Zhang L, Jiang W, Chu CQ, Liu Y. Therapeutic Efficacy of Iguratimod in Patients with Primary Sjogren’s Syndrome [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/therapeutic-efficacy-of-iguratimod-in-patients-with-primary-sjogrens-syndrome/. Accessed December 21, 2016.