Routine blood monitoring in maintenance immunoglobulin treatment of inflammatory neuropathy: Is it clinically relevant?

Abstract

BackgroundPre-treatment screening for IgA deficiency and close monitoring of full blood count (FBC) and urea and electrolytes (U&E) is recommended with intravenous immunoglobulin (IVIg) therapy in neurological diseases. AimsTo examine the frequency of biochemically defined and clinically significant episodes of treatment associated haemolysis, neutropenia, thrombocytopenia and acute renal impairment in a cohort of patients on maintenance Immunoglobulin (Ig) therapy for inflammatory neuropathy. MethodsA retrospective review of routine blood monitoring in a cohort of patients from two UK specialist peripheral nerve centres. Accepted definitions for clinically and biochemically significant haemolysis, neutropenia, thrombocytopenia and acute kidney injury (AKI) were used.Results 1919 infusion episodes in 90 patients were analysed. Age (mean(S.D))= 58.09(14.4)years, 63% male, 72% CIDP (28% MMN), 97% IVIg (3% SCIg). Dose= 1.57 (0.79) g/kg/month or 97.1(37.3)g/infusion, frequency: 3.9 (1.4) weeks.Relative IgA deficiency was noted in 2 individuals (prevalence: 2.2%, 95% C.I.: 0-5.2) who received a combined total of 38 infusions (3800g IVIg) without adverse event. No clinically significant episodes of haemolysis, neutropenia, thrombocytopenia or AKI occurred in relation to treatment. An asymptomatic drop>10g/L haemoglobin (Hb) occurred in 3.5% (95% CI: 2.7-4.3) of treatment episodes in 38 individuals, mean reduction: 17.7(7.4)g/L; lowest Hb: 86g/L. Lower pre-treatment haemoglobin correlated with risk of recurrent episodes Ig-related drop (p:0.007). Two patients with chronic renal failure (stage 1 and 3) had received 28 (IV) and 104 (SC) infusions respectively, (6416g Ig) without impact on estimated glomerular filtration rate (eGFR). ConclusionsNo clinically significant Ig-related events were identified in this representative cohort. We suggest annual screening or clinically indicated testing as safe and more appropriate in long-term Ig use. Screening for IgA deficiency and baseline FBC and U&E may be helpful in identifying those at greater risk of complication.

Incidence and risk factors for intravenous immunoglobulin‐related hemolysis: A systematic review of clinical trial and real‐world populations

“…21 Differences in patient co-morbidities and underlying health conditions may also affect hemolysis risk. [6][7][8]10,11,15,18,19,35,39,43 A high incidence of hemolysis has been observed among studies and case reports in patients with KD: a rare disease where hemolysis risk appears much greater than in most other conditions for which IVIG is indicated. 35,39,43 This increased risk could be related to patients' underlying inflammatory state.…”

“…The reported incidence proportions of hemolysis ranged from 0% to 40% across all realworld studies (Table 1). [6][7][8]10,12,14,15,17,19,20 However, the studies by Tong et al and Pendergrast et al assessed incidence in non-O blood group patients only. 20,21 When these studies were removed to ensure hemolysis incidence was reported as a percentage of all blood groups, the estimated incidence proportions of hemolysis ranged from 0% to 19% in the remaining real-world studies (Table 1).…”

“…Among the 16 observational, real-world studies included in this review, the patient sample size ranged from 16 to over 20,000 patients (Table 1). Patients treated with IVIG were aged between 2 and 85 years old and 52% were male (sex breakdown detailed in 12 studies [6][7][8][9][10][11][12][14][15][16][17]21 ). The most commonly reported conditions treated by IVIG included KD (three studies 7,18,19 ) and dermatologic conditions (two studies 8,16 ).…”

Predicting long‐term trends in inflammatory neuropathy outcome measures using latent class modelling

“…In well-documented patient cohorts, there is marked variation of dosing regimens among patients. 4,[11][12][13] If the neuropathy is in remission, intermittent treatment reduction or cessation is indicated. Small variations between assessments may represent measurement noise.…”

“…A major challenge remains accurately determining ongoing disease activity in the maintenance phase of regular Ig treatment. In well‐documented patient cohorts, there is marked variation of dosing regimens among patients 4,11‐13 . If the neuropathy is in remission, intermittent treatment reduction or cessation is indicated.…”