ABSTRACT
Introduction: Patients with multiple sclerosis (MS) often receive disease-modifying therapies (DMTs) which can reduce the response to vaccines. BNT162b2 (Pfizer-BioNTech) is the first COVID-19 vaccine authorized in Italy but was not evaluated in MS patients receiving DMTs. Objectives: To evaluate serological response and safety to BNT162b2 in patients with MS. Methods: This is an early multicenter, case-control and prospective study. Patients were healthcare workers (HCWs) with MS, receiving at least one DMT, and having received BNT162b2. Blood samples were collected between 2 and 6 weeks after the second vaccine dose and analyzed to quantify anti-Spike antibodies (Abbott). Anti-Spike cut-off for response was set at 7.1 BAU/ ml. Anti-Spike levels in patients considered at-risk of reduced response were compared to those considered non-at-risk, according to literature and expert consensus. Anti-Spike levels were compared to those of a control population of HCWs, without MS or immune-related disease, untreated, and having received BNT162b2. Total follow up was of 9 weeks from the first vaccine dose. Results: From February 2020, 39 MS patients were enrolled. One patient, treated with ocrelizumab, did not develop serological response (1.8 BAU/ml). The remaining patients responded to the vaccine, including two ocrelizumab-treated patients. The control population consisted of 273 HCWs. All controls responded to BNT162b2. Median anti-Spike levels in patients (1471.0 BAU/ ml;range 779.7-2357.0) and controls (1479.0 BAU/ml;range 813.1-2528.0) were comparable. Patients receiving at-risk treatments (n=9;5 fingolimod, 3 ocrelizumab, 1 natalizumab) showed significantly reduced median anti-Spike levels (241.9 BAU/ml;range 40.2-530.0) compared to non-at-risk (n=30;15 dimethyl fumarate, 5 teriflunomide, 4 interferons, 3 glatiramer acetate, 2 cladribine, 1 alemtuzumab) ones (1707.7 BAU/ml;range 1356.2- 2432.8) (p<0.001). No COVID-19 cases were reported. Two patients had a clinical MS relapse after 17 and 30 days after the second dose. A causal relationship with the vaccination could not be established. Conclusions: In our study, most MS patients produce a serological response to BNT162b2 similar to non-MS controls;however, at-risk DMTs resulted in reduced anti-Spike levels and one ocrelizumab- treated patient did not respond. These observations should be better investigated and replicated in larger studies to support clinical decision in COVID-19 vaccine management.
ABSTRACT
Objective: Chloroquine (CLQ)/hydroxychloroquine (HCQ) are two of the most studied drugs for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are very limited data on the effect of treatment of patients affected by rheumatic diseases with HCQ/CLQ and other conventional disease-modifying anti-rheumatic drugs (cDMARDs) on COVID-19. The aim of this study is to investigate the hypothesis that treatment of rheumatic diseases with hydroxychloroquine (HCQ)/chloroquine (CLQ) as compared to other conventional disease-modifying anti-rheumatic drugs (cDMARDs) might decrease the COVID-19-related risk of hospitalization and mortality. Methods: This large-scale case-control study nested within a cohort of cDMARD users was conducted in the Lombardy, Veneto, Tuscany and Lazio regions and Reggio Emilia (Emilia Romagna) Local Health Unit, covering a total of 25.1 million inhabitants. Claims databases were linked to loco-regional COVID-19 surveillance registries from the same catchment area through unique fully-anonymized patient identifiers. Risk of COVID-19-related outcomes was estimated as odds ratios (ORs) along with 95% confidence intervals (CIs), using a multivariate conditional logistic regression analysis, by comparing HCQ/CLQ vs methotrexate (primary comparator) and other cDMARDs (secondary comparator). In addition, the same risk for HCQ/CLQ, methotrexate and other cDMARDs separately vs nonuse of these drugs as well as for presence of rheumatic diseases vs. absence in a non-nested population was investigated. Results: From the cohort of cDMARD users, 1275 cases who were hospitalized due to COVID-19 were identified and matched to 12,734 controls. When compared to recent use of methotrexate, no statistically significant association between recent HCQ/CLQ monotherapy with COVID-19 hospitalization (OR 0.83 [95% CI, 0.69 to 1.00]) or mortality (OR 1.19 [95% CI, 0.85 to 1.67]) was observed. A statistically significant lower risk was found when comparing recent use of HCQ/CLQ to treatment with other cDMARDs and glucocorticoids concomitantly. In the sensitivity analysis in the non-nested population, HCQ/CLQ was not associated with COVID-19 hospitalization as compared with non-use, whereas a mild statistically significant increased risk for recent use of both methotrexate as monotherapy (OR 1.19 [95% CI, 1.05 to 1.34]) or other cDMARDs (OR 1.21 [95% CI, 1.08 to 1.36]) vs non-use was found. Finally, the presence of rheumatoid arthritis or systemic lupus erythematosus was not associated with COVID-19 hospitalization (OR 0.98 [95% CI, 0.89 to 1.07]) or mortality (OR 0.88 [95% CI, 0.74 to 1.05]). Conclusion: Prior exposure to HCQ/CLQ in rheumatic patients was not associated with a protective effect against COVID-19-related hospitalization and mortality. On the contrary, an increased risk in patients receiving other cDMARDs was observed when compared to non-use, especially in those patients concomitantly treated with glucocorticoids. This is likely attributable to a synergistic immunosuppressive effect, leading to increased risk of severe SARS-CoV-2 infection.