Do JAK inhibitors affect immune response to COVID-19 vaccination? Data from the MAJIK-SFR Registry.
Ontology highlight
ABSTRACT:
SUBMITTER: Seror R
PROVIDER: S-EPMC8494471 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
Publications
Do JAK inhibitors affect immune response to COVID-19 vaccination? Data from the MAJIK-SFR Registry.
Seror Raphaèle R Camus Marine M Salmon Jean-Hugues JH Roux Christian C Dernis Emmanuelle E Basch André A Germain Vincent V Leske Charles C Brousseau Steeve S Truchetet Marie-Elise ME Ramon André A Gottenberg Jacques-Eric JE Felten Renaud R Coury Fabienne F Colombey Antoine A Prati Clément C Mariette Xavier X Avouac JérÔme J
The Lancet. Rheumatology 20211006 1
Similar Datasets
Project description:ObjectivesThis study aimed to identify characteristics of patients with rheumatoid arthritis (RA) with an inadequate response to Janus kinase inhibitors (JAKi-IR) and evaluate the efficacy and safety of subsequent treatments.MethodsThis study included 434 patients with RA who started JAKi treatment. JAKi-IR patients were those who switched to another drug due to inadequate response or did not reach low disease activity within 26 weeks of beginning JAKi. The efficacy and safety of switched biological disease-modifying anti-rheumatic drugs (bDMARDs) or cycled targeted synthetic disease-modifying anti-rheumatic drugs were analysed 26 weeks after switching treatment in JAKi-IR patients.ResultsPatients with JAKi-IR RA accounted for 31.8% (n=138/434). Multiple logistic regression identified factors contributing to JAKi-IR, such as the prior use of multiple ineffective bDMARDs and suboptimal JAKi dosing. There were no differences in patient background when comparing patients with RA with JAKi-IR who cycled to another JAKi (n=31) versus those who switched to bDMARDs (n=45). Among those cycling to another JAKi, the Clinical Disease Activity Index (CDAI) scores improved by week 26, with higher remission rates, while retention and adverse events remained similar. Trajectory analysis identified three CDAI response patterns, with the 'treatment response' group showing rapid and sustained improvement when cycling to another JAKi. Multiple logistic regression in this group identified another JAKi cycle as the critical factor for the treatment response.ConclusionsCycling JAKis is more effective than switching to bDMARDs in JAKi-IR RA, with no differences in safety or retention. This study suggests that cycling to another JAKi may be appropriate for patients with RA with JAKi-IR.
| S-EPMC11759213 | biostudies-literature
Project description:ObjectiveTo examine the course of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) in France on treatment with Janus kinase inhibitors (JAKis) using the MAJIK-SFR registry.MethodsProspective national multicentre observational study identifying patients with RA-ILD from the MAJIK-SFR registry. Pulmonary assessment data were collected at JAKi initiation and follow-up visits (6 months, 12 months and a median of 21 months postinclusion), including chest high-resolution CT (HRCT), pulmonary function tests (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)), acute exacerbations of ILD, respiratory infections and lung cancers.ResultsWe enrolled 42 patients (26 women, 62%) with RA-ILD with a mean age of 61±13 years and a mean disease duration of 16±10 years. Compared with the 778 RA patients without ILD from the MAJIK registry, RA-ILD patients were older, displayed more severe and active disease and had more prevalent comorbidities. Non-specific interstitial pneumonia and usual interstitial pneumonia accounted for 46% and 43% of the chest HRCT ILD patterns, respectively. No significant changes in FVC and DLCO were observed during the follow-up period. Chest HRCT lesions remained stable in 69% of patients. Progressive ILD was identified in 8 patients (19%). 16 (38%) respiratory tract infections were observed. Only one acute regressive exacerbation of ILD was noted, and no lung cancer was diagnosed. No deaths occurred. JAKi was discontinued in 17 patients including 8 for inefficacy on joint involvement and 5 for intolerance.ConclusionThe analysis indicates stability of RA-ILD in patients treated with JAKi. The tolerance profile of JAKi in this higher risk population did not reveal new safety signal.
| S-EPMC11749054 | biostudies-literature
Project description:During SARS-CoV-2 infection, the innate immune response can be inhibited or delayed, and the subsequent persistent viral replication can induce emergency signals that may culminate in a cytokine storm contributing to the severe evolution of COVID-19. Cytokines are key regulators of the immune response and virus clearance, and, as such, are linked to the-possibly altered-response to the SARS-CoV-2. They act via a family of more than 40 transmembrane receptors that are coupled to one or several of the 4 Janus kinases (JAKs) coded by the human genome, namely JAK1, JAK2, JAK3, and TYK2. Once activated, JAKs act on pathways for either survival, proliferation, differentiation, immune regulation or, in the case of type I interferons, antiviral and antiproliferative effects. Studies of graft-versus-host and systemic rheumatic diseases indicated that JAK inhibitors (JAKi) exert immunosuppressive effects that are non-redundant with those of corticotherapy. Therefore, they hold the potential to cut-off pathological reactions in COVID-19. Significant clinical experience already exists with several JAKi in COVID-19, such as baricitinib, ruxolitinib, tofacitinib, and nezulcitinib, which were suggested by a meta-analysis (Patoulias et al.) to exert a benefit in terms of risk reduction concerning major outcomes when added to standard of care in patients with COVID-19. Yet, only baricitinib is recommended in first line for severe COVID-19 treatment by the WHO, as it is the only JAKi that has proven efficient to reduce mortality in individual randomized clinical trials (RCT), especially the Adaptive COVID-19 Treatment Trial (ACTT-2) and COV-BARRIER phase 3 trials. As for secondary effects of JAKi treatment, the main caution with baricitinib consists in the induced immunosuppression as long-term side effects should not be an issue in patients treated for COVID-19.We discuss whether a class effect of JAKi may be emerging in COVID-19 treatment, although at the moment the convincing data are for baricitinib only. Given the key role of JAK1 in both type I IFN action and signaling by cytokines involved in pathogenic effects, establishing the precise timing of treatment will be very important in future trials, along with the control of viral replication by associating antiviral molecules.
| S-EPMC9035837 | biostudies-literature
Project description: Not available
| S-EPMC8975261 | biostudies-literature
Project description:This study evaluated the immune response to vaccination against COVID-19 in 534 healthcare frontline workers in Vilnius, Lithuania. The incidence of COVID-19 was reduced significantly after vaccination started in the healthcare sector. SARS-CoV-2 antibodies were detected in groups V-VII and this level of antibodies was found to be effective in preventing COVID-19. Sustained immune response was achieved after two vaccination doses, which remained stable for up to 6 months. After the booster dose, antibody levels remained high for an additional 12 months. Although SARS-CoV-2 antibody levels decreased after 6 months, even lower levels of antibodies provided protection against the Delta strain. The booster dose distributed the antibody titer in the high-level antibody groups, offering maximum protection at 12 months. However, even individuals with high antibody titers were observed to contract COVID-19 after vaccination with a booster dose and 6 months in the presence of the Omicron strain. Unfortunately, high levels of antibodies did not provide protection against the new strain of COVID-19 (the Omicron variant), posing a risk of infection. When comparing the antibody titer of vaccinated participants without COVID-19 and those with COVID-19, the change in antibodies after vaccination was significantly lower in infected participants. Individuals with comorbidities and specific conditions had lower antibody levels.
| S-EPMC10891992 | biostudies-literature
Project description:Introduction La réponse vaccinale chez les patients atteints de maladies auto-immunes et inflammatoires peut être fortement impactée sous certains traitements de fond, tels que le RTX. À ce jour, peu de données sont disponibles concernant les JAK inhibiteurs (JAKi), et aucune en lien avec la vaccination anti-SARS-CoV-2. L’objectif de cette étude était d’étudier la réponse vaccinale anti-SARS-CoV-2 chez des patients sous JAKi. Patients et méthodes Dans cette étude ancillaire du registre MAJIK-SFR (NCT04602091), les patients toujours sous anti-JAKi au moment de la vaccination et ayant eu une sérologie anti-SARS-CoV-2 effectuée au moins 2 semaines après un schéma vaccinal complet (2 injections du vaccin Pfizer, Moderna ou AstraZeneca, ou 1 injection du vaccin Janssen, ou infection COVID-19 suivi d’une injection de n’importe quel vaccin). Les taux d’anticorps IgG ou totaux anti-protéine spike (S1, S1/S2 ou RBD) ont été détectés à l’aide de kits commerciaux utilisant majoritairement la technique d’immunoanalyse par chimiluminescence, ou dans 4 cas par ELISA ou enzyme linked fluorescence assay (ELFA). Le patient était considéré répondeur si le taux d’anticorps détecté était ≥ au seuil de positivé du kit. Les caractéristiques des patients ont été comparées entre les répondeurs et non-répondeurs afin d’identifier les facteurs associés a la non-réponse. Résultats Cent treize patients ont été inclus (98 [86,7 %] atteints de PR, 15 [13,4 %] de PsA) dont 56 (49,6 %) sous baricitinib, 30 (26,5 %) sous tofacitinib et 27 (23,9 %) sous upadacitinib. Quatre-vingt-dix-sept (85,8 %) patients ont reçu une vaccination par vaccin à ARNm (Pfizer ou Moderna). Neuf patients avaient eu une infection COVID avant la vaccination. Cinq patients ont reçu une 3e dose. La réponse vaccinale a été évaluée en moyenne 8,7 semaines (±5,2) après la dernière injection. Le taux de séroconversion était de 88,5 %. Le taux de non-réponse était plus élevé sous upadacitinib (n = 7/27, 25,9 %, p = 0,013) comparé au baricitinib (n = 5/56, 8,9 %) ou tofacitinib (n = 1/30, 3,3 %). Les non-répondeurs étaient plus âgés que les répondeurs (p = 0,02), mais l’âge moyen à la vaccination était similaire pour chaque JAKi. Sous barictinib et tofacitinib les non-répondeurs avaient tous ≥ 65 ans ; 4 des 7 non-répondeurs sous upadacitinib avaient moins de 65 ans. L’intervalle entre la dernière injection et la sérologie était légèrement plus long chez les non-répondeurs (11,25 ± 5,94 vs 8,32 ± 5,01, p = 0,099). Aucun autre paramètre (utilisation concomitante de MTX ou corticostéroïdes, dose de JAKi, activité de la maladie, type de vaccin) n’était associé à une non-réponse. Un antécédent de traitement par RTX (n = 18, 15,9 %) n’avait pas non plus d’impact sur la réponse vaccinale ; néanmoins, la dernière injection datait de ≥ 6 mois avant la vaccination chez tous les patients. Conclusion Le taux de séroconversion après vaccination anti-SARS-CoV-2 chez les patients traités par JAKi reste élevé (88,5 %). Cependant, la non-réponse peut survenir principalement chez les patients âgés ≥ 65 ans. De plus, l’upadacitinib était associé à un taux de non-réponse plus élevé (25,9 %). Ces résultats doivent être confirmés mais suggèrent que chez les patients sous JAKi de ≥ 65 ans ou traités par upadacitinib, une évaluation sérologique pourrait être discuter pour guider la décision clinique (3e dose de vaccin et/ou vaccination familiale). L’évaluation de la réponse immunitaire cellulaire chez les non-répondeurs sera également intéressante pour déterminer si une autre forme d’immunité peut avoir été acquise.
| S-EPMC8626125 | biostudies-literature
Project description:BackgroundThe innate immune response is important for the development of the specific adaptive immunity, however it may also be associated with reactogenicity after vaccination. We explore the association between innate responsiveness, reactogenicity, and antibody response after first COVID-19 vaccination.MethodsWe included 146 healthy Dutch individuals aged 12-59 who received their first BNT162b2 (Comirnaty, Pfizer) COVID-19 vaccination. Data on reactogenicity were collected for each individual through daily questionnaires from day 0-5 after vaccination. From 60 participants, serum (adults) and plasma (adolescents) samples were collected before and/or 2 ± 1 days after vaccination to measure cytokines/chemokines as markers for innate responsiveness. Each individual was categorised into innate low, intermediate and high responder based on above or below the median value for each analyte detected after vaccination. For 137 participants, serum was collected at day 28 after vaccination for Spike S1- and RBD-antibody concentration. The associations between reactogenicity and/or innate responsiveness and/or log-transformed antibody concentration were explored using logistic and linear regressions.ResultsMost participants (85 %) reported both local and systemic symptoms after vaccination. Two participants reported no symptoms. More than half (54 %) reported one or more moderate symptoms. Significantly higher levels of pro-inflammatory mediators CXCL9, CXCL10, CXCL11, IFNγ and CCL20 in adults, and CXCL9, CXCL10 and CXCL11 in adolescents, were found after vaccination. Participants who showed high innate immune responsiveness had higher odds (OR 6.0; 95 % CI 1.4-33) of experiencing one or more moderate symptoms. No association was found between innate responsiveness or having one or more moderate symptoms with Spike S1- or RBD-antibody concentration at day 28 after vaccination.ConclusionOur results suggest an association between the strength of the innate immune response and the severity of reactogenicity to SARS-CoV-2 vaccination. However, more research is needed to understand the relation between reactogenicity and immunogenicity of COVID-19 vaccines.
| S-EPMC11681879 | biostudies-literature
Project description:ObjectiveThe current study aimed to identify the association between COVID-19 vaccination and prolonged post-COVID symptoms (long-COVID) in adults who reported suffering from this condition.MethodsThis was a retrospective follow-up study of adults with long-COVID syndrome. The data were collected during a phone call to the participants in January-February 2022. We inquired about their current health status and also their vaccination status if they agreed to participate.ResultsIn total, 1236 people were studied; 543 individuals reported suffering from long long- COVID (43.9%). Chi square test showed that 15 out of 51 people (29.4%) with no vaccination and 528 out of 1185 participants (44.6%) who received at least one dose of any vaccine had long long- COVID symptoms (p = 0.032).ConclusionsIn people who have already contracted COVID-19 and now suffer from long-COVID, receiving a COVID vaccination has a significant association with prolonged symptoms of long-COVID for more than one year after the initial infection. However, vaccines reduce the risk of severe COVID-19 (including reinfections) and its catastrophic consequences (e.g., death). Therefore, it is strongly recommended that all people, even those with a history of COVID-19, receive vaccines to protect themselves against this fatal viral infection.
| S-EPMC10849259 | biostudies-literature
Project description:BackgroundInnate immune cells play a crucial role in the pathophysiology of rheumatoid arthritis (RA) via release of cytokines. Small-molecule inhibitors of Janus kinases (JAKi) are clinically efficacious in patients with RA. However, the isoform-specific action of each JAKi is difficult to assess, since JAKs form heterodimeric complexes with cytokine receptors. We assessed the effects of several JAKi on GM-CSF-primed human innate immune cells.ResultsTreatment with JAKi (tofacitinib, baricitinib, upadacitinib) prevented GM-CSF-induced JAK2/STAT5 phosphorylation at higher concentrations (400 nM) in THP-1 cells. Whereas compared with baricitinib or upadacitinib, the inhibitory effects of tofacitinib on the GM-CSF-induced JAK2/STAT5 phosphorylation were weak at lower concentrations (≤ 100 nM). All JAKi inhibited GM-CSF-induced IL-1β production by human neutrophils. However, the inhibitory effects of baricitinib on IL-1β production were larger compared to those of tofacitinib or upadacitinib at lower concentrations (≤ 100 nM). Similarly, all JAKi inhibited GM-CSF-induced caspase-1(p20) production by human neutrophils.ConclusionWe conclude that incubation with JAKi prevents GM-CSF-mediated JAK2/STAT5 activation in human innate immune cells. Although baricitinib and upadacitinib almost completely blocked GM-CSF-mediated JAK2/STAT5 signaling, the inhibitory effects of tofacitinib were weaker at lower concentrations suggesting that variation exists among these JAKi in the inhibition of JAK2 signaling pathways.
| S-EPMC7296727 | biostudies-literature
Project description:In India, COVID-19 (Corona Virus Disease-2019) continues to this day, although with subdued intensity, following two major waves of viral infection. Despite ongoing vaccination drives to curb the spread of COVID-19, the relative potential of the administered vaccines to render immune protection to the general population and their advantage over natural infection remain undocumented. In this study, we examined the humoral and cell-mediated immune responses induced by the two vaccines Covishield and Covaxin, in individuals living in and around Kolkata, India. We also compared the immune responses induced separately by vaccination and natural infection. Our results indicate that although Covishield generates a better humoral immune response toward SARS-CoV-2, both vaccines are almost equivalent in terms of cell-mediated immune response to the virus. Both Covishield and Covaxin, however, are more effective toward the wild-type virus than the Delta variant. Additionally, the overall immune response resulting from natural infection in and around Kolkata is not only similar to that generated by vaccination but the cell-mediated immune response to SARS-CoV-2 also lasts for at least ten months in some individuals after the viral infection.
| S-EPMC10257406 | biostudies-literature