Effect of in utero hydroxychloroquine exposure on the development of cutaneous neonatal lupus erythematosus.

OBJECTIVE: Cutaneous neonatal lupus (cNL) occurs in possibly 5%-16% of anti-Ro±anti-La antibody-exposed infants. Data suggest in utero exposure to hydroxychloroquine (HCQ) may prevent cardiac NL. The aim was to assess whether in utero exposure to HCQ decreases the risk of cNL and/or delays onset. METHODS: A multicentre case-control study was performed with 122 cNL cases and 434 controls born to women with a rheumatological disease who had documentation of maternal anti-Ro±anti-La antibodies at pregnancy and confirmation of medication use and the child's outcome. A secondary analysis was performed on 262 cNL cases, irrespective of maternal diagnosis, to determine if HCQ delayed time to cNL onset. RESULTS: Twenty (16%) cNL cases were exposed to HCQ compared with 146 (34%) controls (OR 0.4 (95% CI 0.2 to 0.6); p<0.01). Exposure to HCQ was associated with a reduced risk of cNL; exposure to anti-La antibody and female gender were associated with an increased risk of cNL. Exposure to HCQ remained significantly associated with a reduced cNL risk in the analyses limited to mothers with systemic lupus erythematosus and those who developed rash ≤1 month. When analysing all 262 cNL cases, HCQ-exposed infants were older (6.0 (95% CI 5.7 to 6.3) weeks) at cNL onset versus HCQ-non-exposed infants (4.4 (95% CI 3.9 to 5.0) weeks), but the difference was not statistically significant (p=0.21). CONCLUSION: Exposure to HCQ was associated with a reduced risk of cNL. Among cNL cases, those exposed to HCQ tend to have later onset of rash. Both findings suggest a protective effect of HCQ on cNL.

Pegloticase in gout treatment - safety issues, latest evidence and clinical considerations.

Gout is a common rheumatic condition, with increasing prevalence in recent decades. The mainstay of treatment for gout is oral urate-lowering therapy (ULT), typically with xanthine oxidase inhibitors (XOIs). Unfortunately, a proportion of patients have persistent gout that is refractory to ULT. Pegloticase, a recombinant pegylated uricase, has been approved by the US Food and Drug Administration for the treatment of refractory gout. However, concern has been raised regarding the risk of infusion reactions, which are now understood to be largely due to the development of antipegloticase antibodies. Discontinuation of pegloticase upon failure to lower serum urate has been shown to markedly reduce infusion reaction risk, but deprives patients of what, in many cases, is a last-resort treatment. In this manuscript, we review the rationale, mechanism of action, efficacy and safety of pegloticase. Additionally, we focus on potential strategies to reduce pegloticase immunogenicity and potentially make this important agent available to a wider group of patients requiring treatment.

Pegloticase failure and a possible solution: Immunosuppression to prevent intolerance and inefficacy in patients with gout.

INTRODUCTION: Pegloticase is a highly effective therapy for patients with refractory and/or tophaceous gout, but has a high discontinuation rate (30-50%) due to development of anti-drug antibodies causing loss of efficacy and risk of infusion reactions. OBJECTIVE: To describe the use of azathioprine or other immunosuppressive therapies as a pegloticase adjunct to prevent pegloticase immunogenicity when treating gout. METHODS: Case report of azathioprine use in a patient receiving pegloticase therapy for refractory tophaceous gout, and review of the literature for the impact of immunosuppressive agents on development of anti-drug antibodies. RESULTS: A 56-year-old man with severe refractory tophaceous gouty arthritis was placed on low-dose azathioprine (50mg daily) in combination with pegloticase, with successful treatment after 98 weeks illustrated by significant improvement of caliper-measured tophi (77% decrease), resolution of gouty attacks, maintenance of low serum urate (sUA) level, absence of infusion reactions, and good toleration of the treatment by the patient. Two transient increases in sUA (maximal sUA 1.0 and 6.2mg/dL, respectively), were associated with azathioprine non-compliance and resolved with azathioprine reinstitution. Literature review confirmed successful use of DMARDs for prevention of anti-drug antibodies to anti-TNF-α therapies in RA, spondyloarthropathies, and inflammatory bowel disease. Additionally, one open-label trial of pegloticase for refractory tophaceous gout included 7 organ transplant recipients on immunosuppressive medications (mycophenolate mofetil, cyclosporine, azathioprine, and/or tacrolimus), only one of whom (14%) was noted to experience treatment failure (anti-pegloticase antibodies and loss of urate-lowering efficacy without infusion reaction), versus 52% (n =12) of non-immunosuppressed subjects (n = 23). CONCLUSIONS: Low doses of oral immunosuppressive therapy may provide a safe, cost-effective adjunct to prevent the development of anti-drug antibodies associated with infusion reactions and high rate of pegloticase failure in patients with refractory gout. Controlled studies to assess an immunosuppressive strategy when using pegloticase are warranted.

Gout and Osteoarthritis: Associations, Pathophysiology, and Therapeutic Implications.

Osteoarthritis (OA), the most common type of arthritis worldwide, is a degenerative disease of diarthrodial joints resulting in pain, reduced quality of life, and socioeconomic burden. Gout, the most common form of inflammatory arthritis, is a consequence of persistently elevated levels of urate and the formation of proinflammatory monosodium urate crystals in joints. Clinicians have long noted a predilection for both diseases to occur in the same joints. In this review, we provide an overview into research elucidating possible biochemical, mechanical, and immunological relationships between gout and OA. We additionally consider the potential implications of these relationships for OA treatment.