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AIMS: We describe the varied clinical presentations, barriers in diagnosis and outcomes of anti-HMGCR myopathy in a large national cohort. METHODS: Adults found positive for serum anti-HMGCR autoantibodies via line blot or enzyme-immunoassay followed by immunoprecipitation were included in the study. RESULTS: Of 75 patients identified, the records of 72 (96 %) described weakness as the presenting symptom. The records of 65 gave a reliable description of proximal weakness. In 22/65 (33.8 %) the weakness was described as predominantly or solely lower limb weakness. Forty-five of 75 (60 %) presented with a subacute onset (duration of symptoms >4 weeks -≤6 months), whilst 22/75 (29.3 %) presented with a more indolent chronic onset (duration of symptoms >6 months). Eighteen of 75 (24 %) suffered falls and 2/75 (2.7 %) had "general decline". In three patients no weakness was described: two presented with myalgia and one with a skin rash characterized as Jessner lymphocytic skin rash. Median creatine kinase at presentation was 7337 U/L (range 1050-25,500). Muscle biopsy was performed in 38 (50.7 %). Associated malignancy was infrequent. Four patients recovered without immunosuppression. Five-year and 10-year survival was 92.7 % (95 % CI 80.6-97.4 %), and 82.5 % (95 % CI 61.2-92.8 %) respectively. CONCLUSION: Recurrent falls, a long prodrome and dominant lower limb proximal weakness were common in this anti-HMGCR myopathy cohort. These features overlap with frailty syndrome and sporadic inclusion body myositis emphasizing the importance of considering anti-HMGCR myopathy in that clinical context. A minority of patients recover after statin withdrawal alone.

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BACKGROUND: In 2014 the incidence of anti-HMGCR myopathy in New Zealand was ∼1.7 case/million persons/year. OBJECTIVE: Re-estimate the population incidence and assess ethnic variation in those >40-year -olds. SETTING: An incidence cohort was defined by seropositivity for immunoprecipitating anti-HMGCR autoantibodies tested at a national reference laboratory between 1 October 2019-30 September 2021.Separately, ethnicity standardized incidence in > 40-year-olds discharged from New Zealand public hospitals for idiopathic and unspecified myopathy (ICD AM codes M60.8/60.9), was examined for concordance. RESULTS: The forty patients identified in the incidence cohort were all >40-years-old and all had a prior history of statin use. Annual incidence was 4 cases/million/year (95%CI 2.8-5.5). In those >40 years the incidence in Polynesians (Maori and Pacific peoples combined) was 25cases/million/year (95% CI 15.9 -40.1), in Asians 5.7cases/million/year (95% CI 0.7 -20.5) and in Europeans 7cases/million/year (95% CI 3.1 -8.4). The risk in statin users aged > 40 years was ∼1/9000 in Polynesians and ∼1/48000 in Europeans.Ethnic difference in incidence of idiopathic and unspecified myopathy (ICD AM codes M60.8/60.9) was also found in hospital discharges. CONCLUSION: In the past half decade the estimated incidence of anti-HMGCR myopathy in New Zealand has doubled. Polynesian peoples of New Zealand >40-years-old have an estimated 5-fold higher risk compared with European and Asian peoples. The estimated absolute risk in statin users >40-year-olds was 108 cases/million/year in Polynesians vs 21 cases/million/year in Europeans.

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BACKGROUND: Detecting antidrug antibodies (ADAs) against infliximab or adalimumab is useful for therapeutic drug monitoring. Various ADA detection methods exist, and antibody titer is an output in some algorithms. Homogenous mobility shift assay (HMSA) measures relative ADA concentration and determines drug-ADA complex size in vitro. However, the relevance of complex size determination in drug monitoring remains unclear. Hence, the association between complex size, ADA concentration, and sample detectable neutralizing activity was evaluated. METHODS: Sera from infliximab-treated and adalimumab-treated patients who tested positive for ADA in the National Screening Service were analyzed using 3 ADA assays. HMSA determined the relative ADA concentrations and complex sizes, competitive ligand-binding assay evaluated the sample neutralizing capacity, and enzyme-linked immunosorbent assay detected immunoglobulin (Ig)G4 ADA. RESULTS: Most ADA-positive samples (>80%) formed drug-ADA dimer complexes, whereas 17% had dimer and multimer complexes, and 3% had multimeric complexes. Multimer presence had 100% positive predictive value for detectable neutralizing activity. ADA concentration and detectable neutralizing activity were moderately correlated (r = 0.65) in adalimumab-treated patients and strongly correlated (r = 0.81) in infliximab-treated patients. In adalimumab-treated patients, multimer presence was a stronger predictor of neutralizing activity than ADA concentration was, but not in infliximab-treated patients. However, in infliximab-treated patient samples, multimer presence revealed a distinct subset with high ADA concentrations, neutralizing activity, and IgG4 ADA. CONCLUSIONS: Multimers detected using HMSA had a strong positive predictive value for competitive ligand-binding assay detectable neutralizing activity. Multimeric IgG4-containing ADA-drug complexes revealed a distinct subset of infliximab-treated patient samples, whose clinical relevance merits further investigation.

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AIMS: Cardiac sarcoidosis (CS) is an important cause of mortality in patients with sarcoidosis. The aim of this retrospective cohort study was to characterize the prevalence, incidence, clinical features and outcomes of CS in the southern region of New Zealand. METHODS AND RESULTS: 45 patients were identified: 23 fulfilling international classification criteria, 9 fulfilling physician consensus criteria, and 13 classified as possible CS. As of June 2021, 26 patients were living and domiciled in the Canterbury district; estimated point prevalence was 4.43 cases per 100,000 people. The average annual incidence was 0.24 cases per 100,000 people between 2016 and 2020. We estimated a 5.14% frequency of CS in patients with sarcoidosis. Median age at presentation was 56 years (range 31-72). Common presentations included heart failure, heart block and life threatening ventricular and supraventricular arrhythmias. Electrocardiogram abnormalities were found in 93.3% and cardiac MRI was often relied upon by physicians for diagnosis. The 10-year survival was 94% (95% CI 78-99%). CONCLUSION: Our study provides further insight into the epidemiology of CS. In this retrospective cohort the frequency of CS amongst patients with sarcoidosis was estimated at 5%, whilst the estimated point prevalence of the disease was twice that of a contemporary report from the Northern hemisphere. The 10-year survival was similar to contemporaneous reports from other developed countries.

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