Background and Objectives: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced... Show moreBackground and Objectives: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Delta) and baseline values in predicting the development of SSc-ILD. Methods: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (+/- 4) (t1) and 24 (+/- 4) (t(2)) months. Results: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t(2). Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t(2) (p = 0.0031). Neither the mean t0 to t1 change (Delta) of DLCO nor the mean t(0) to t(1) FVC Delta predicted the appearance of ILD at t(2). Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (+/- 4) months, we observed a moderate predictive capability of t(0) DLCO < 80%, stronger than that of FVC < 80%. Conclusions: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc. Show less
Winchow, L.L.; Tikly, M.; Musenge, E.; Chopra, A.; Huizinga, T.W.J.; Salomon-Escoto, K.; ... ; Govind, N. 2023
Background: We investigated sensitivity to change of three scoring methods of the Health Assessment Questionnaire (HAQ) in relation to change in disease activity in patients with active rheumatoid... Show moreBackground: We investigated sensitivity to change of three scoring methods of the Health Assessment Questionnaire (HAQ) in relation to change in disease activity in patients with active rheumatoid arthritis (RA).Patients and Methods: Adult RA-patients with complete data in the Measurement of Efficacy of Treatment in the Era of Outcome in Rheumatology database with respect to the 20 HAQ questions and disease activity score with 28-joint count using the erythrocyte sedimentation rate (DAS28-ESR) for 2 visits, at least 6-12 months apart, and high disease activity (DAS28-ESR >5.1) at visit 1. Changes in HAQ scored by the (1) conventional method (HAQ-8), (2) HAQ-Tomlin method (HAQ-T), and (3) HAQ-20-item method (HAQ-20) were analyzed in relation to the European League Against Rheumatism (EULAR) RA response criteria, dichotomized to good/moderate and no response.Results: In 421 patients, mean standard deviation (SD) DAS28-ESR declined significantly (6.1 [0.8]-4.8 [1.6], P < 0.0001), over a mean period (SD) of 8.7 (1.9) months. Median HAQ scores improved by all three scoring methods, HAQ-8 (1.6-1.4); HAQ-T (1.2-0.7); and HAQ-20 (1.2-0.9) with similar effect sizes of 0.97, 0.96, and 0.95, respectively. The proportion who achieved a HAQ minimally clinically important improvement (MCII) of >= 0.22 was significantly higher in 47% of patients with EULAR good/moderate score compared to the no response patients (64% vs. 11%, P < 0.0001). Good/moderate EULAR response, higher baseline DAS28, and higher baseline HAQ (7.11, 1.55, and 1.06, respectively) were independent predictors of achieving a HAQ-MCII.Conclusion: Three HAQ scoring methods performed similarly in sensitivity to change with no advantage of alternative scoring methods compared to the conventional HAQ-8 method. A good/moderate EULAR response, despite long disease duration, was associated with a significant likelihood of achieving a HAQ-MCII. Show less
Moel, E.C. de; Trouw, L.A.; Terao, C.; Govind, N.; Tikly, M.; El-Gabalawy, H.; ... ; Woude, D. van der 2023
Background: Rheumatoid arthritis (RA) occurs across the globe in different ethnic populations. Most RA patients harbor anti-modified protein antibodies (AMPA); however, it is unclear whether... Show moreBackground: Rheumatoid arthritis (RA) occurs across the globe in different ethnic populations. Most RA patients harbor anti-modified protein antibodies (AMPA); however, it is unclear whether differences exist in autoantibody responses at different geographic locations and between different ethnic groups, which could provide new clues regarding factors underlying autoantibody development. We therefore investigated AMPA prevalence and association with HLA DRB1 alleles and smoking in four ethnically diverse populations on four different continents. Methods: Anti-carbamylated (anti-CarP), anti-malondialdehyde acetaldehyde (anti-MAA), and anti-acetylated protein antibodies (anti-AcVim) IgG were determined in anti-citrullinated protein antibody-positive Dutch (NL, n = 103), Japanese (JP, n = 174), First Nations Peoples in Canada (FN, n = 100), and black South African (SA, n = 67) RA patients. Ethnicity-matched local healthy controls were used to calculate cut-offs. Risk factors associated with AMPA seropositivity in each cohort were identified using logistic regression. Results: Median AMPA levels were higher in First Nations Peoples in Canada and especially South African patients, as reflected by percentage seropositivity: NL, JP, FN, and SA: anti-CarP: 47%, 43%, 58%, and 76% (p < 0.001); anti-MAA: 29%, 22%, 29%, and 53% (p < 0.001); and anti-AcVim: 20%, 17%, 38%, and 28% (p < 0.001). Total IgG levels also differed markedly, and when autoantibody levels were normalized to total IgG, differences between cohorts became less pronounced. Although there were some associations with AMPA and HLA risk alleles and smoking, none was consistent across all four cohorts. Conclusions: AMPA against various post-translational modifications could consistently be detected on different continents across ethnically diverse RA populations. Differences in AMPA levels corresponded to differences in total serum IgG levels. This suggests that, despite differences in risk factors, a common pathway may be involved in AMPA development across geographic locations and ethnicities. Show less
Moel, E.C. de; Trouw, L.A.; Terao, C.; Govind, N.; Tikly, M.; El-Gabalawy, H.; ... ; Woude, D. van der 2023
BackgroundRheumatoid arthritis (RA) occurs across the globe in different ethnic populations. Most RA patients harbor anti-modified protein antibodies (AMPA); however, it is unclear whether... Show moreBackgroundRheumatoid arthritis (RA) occurs across the globe in different ethnic populations. Most RA patients harbor anti-modified protein antibodies (AMPA); however, it is unclear whether differences exist in autoantibody responses at different geographic locations and between different ethnic groups, which could provide new clues regarding factors underlying autoantibody development. We therefore investigated AMPA prevalence and association with HLA DRB1 alleles and smoking in four ethnically diverse populations on four different continents.MethodsAnti-carbamylated (anti-CarP), anti-malondialdehyde acetaldehyde (anti-MAA), and anti-acetylated protein antibodies (anti-AcVim) IgG were determined in anti-citrullinated protein antibody-positive Dutch (NL, n = 103), Japanese (JP, n = 174), First Nations Peoples in Canada (FN, n = 100), and black South African (SA, n = 67) RA patients. Ethnicity-matched local healthy controls were used to calculate cut-offs. Risk factors associated with AMPA seropositivity in each cohort were identified using logistic regression.ResultsMedian AMPA levels were higher in First Nations Peoples in Canada and especially South African patients, as reflected by percentage seropositivity: NL, JP, FN, and SA: anti-CarP: 47%, 43%, 58%, and 76% (p < 0.001); anti-MAA: 29%, 22%, 29%, and 53% (p < 0.001); and anti-AcVim: 20%, 17%, 38%, and 28% (p < 0.001). Total IgG levels also differed markedly, and when autoantibody levels were normalized to total IgG, differences between cohorts became less pronounced. Although there were some associations with AMPA and HLA risk alleles and smoking, none was consistent across all four cohorts.ConclusionsAMPA against various post-translational modifications could consistently be detected on different continents across ethnically diverse RA populations. Differences in AMPA levels corresponded to differences in total serum IgG levels. This suggests that, despite differences in risk factors, a common pathway may be involved in AMPA development across geographic locations and ethnicities. Show less
Dekkers, J.S.; Bergstra, S.A.; Chopra, A.; Tikly, M.; Fonseca, J.E.; Salomon-Escoto, K.; ... ; Woude, D. van der 2019
