Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
1.
Ann Rheum Dis ; 81(6): 889-897, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1709161

ABSTRACT

OBJECTIVE: To evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in patients with rheumatoid arthritis (RA). METHODS: This was a single-centre, prospective, randomised, investigator-blinded, intervention study (NCT04754698, CoronavRheum) including adult patients with RA (stable Clinical Disease Activity Index (CDAI) ≤10, prednisone ≤7.5 mg/day) randomised (1:1) to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at day 0 (D0), D28 and D69. Coprimary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralising antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titres (GMT) and flare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and for safety reasons those who flared at D28 (CDAI >10) and did not withdraw MTX twice. RESULTS: Randomisation included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations). Safety evaluation included 60 patients in the MTX-hold and 69 patients in the MTX-maintain group. Further exclusions included 27 patients (13 (21.7%) vs 14 (20.3%), p=0.848) with positive baseline IgG/NAb and 10 patients (21.3%) in MTX-hold with CDAI >10 at D28. At D69, the MTX-hold group (n=37) had a higher rate of SC than the MTX-maintain group (n=55) (29 (78.4%) vs 30 (54.5%), p=0.019), with parallel augmentation in GMT (34.2 (25.2-46.4) vs 16.8 (11.9-23.6), p=0.006). No differences were observed for NAb positivity (23 (62.2%) vs 27 (49.1%), p=0.217). At D28 flare, the rates were comparable in both groups (CDAI, p=0.122; Disease Activity Score in 28 joints with C reactive protein, p=0.576), whereas CDAI >10 was more frequent in MTX-hold at D69 (p=0.024). CONCLUSION: We provided novel data that 2-week MTX withdrawal after each dose of the Sinovac-CoronaVac vaccine improves anti-SARS-CoV-2 IgG response. The increased flare rates after the second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of flares.


Subject(s)
Arthritis, Rheumatoid , COVID-19 Vaccines , COVID-19 , Methotrexate , Adult , Antibodies, Neutralizing , Antibodies, Viral , Arthritis, Rheumatoid/drug therapy , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Humans , Immunoglobulin G , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Prospective Studies , SARS-CoV-2 , Withholding Treatment
2.
Ann Rheum Dis ; 80(11): 1376-1384, 2021 11.
Article in English | MEDLINE | ID: covidwho-1462911

ABSTRACT

OBJECTIVES: There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of 'usual' (5 mg every 4 weeks) versus 'fast' (5 mg every 2 weeks) escalation of oral MTX. METHODS: This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat. RESULTS: 178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen. CONCLUSION: A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially. TRIAL REGISTRATION NUMBER: CTRI/2018/12/016549.


Subject(s)
Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Methotrexate/administration & dosage , Adolescent , Adult , Arthritis, Rheumatoid/physiopathology , Chemical and Drug Induced Liver Injury/epidemiology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/epidemiology , Humans , Leukopenia/chemically induced , Leukopenia/epidemiology , Male , Methotrexate/analogs & derivatives , Methotrexate/blood , Middle Aged , Polyglutamic Acid/analogs & derivatives , Polyglutamic Acid/blood , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Treatment Outcome , Young Adult
3.
BMJ Case Rep ; 14(1)2021 Jan 07.
Article in English | MEDLINE | ID: covidwho-1015617

ABSTRACT

Symptomatic drug-induced liver injury (DILI) is an uncommon problem. Direct DILI is dose-related, predictable with short latency (hour to days) and is generally associated with transient and reversible transaminitis without jaundice. Antimetabolites including methotrexate are a common cause for direct DILI. Hepatotoxicity associated with high-dose methotrexate (HD-MTX) is generally transient and includes reversible elevation of transaminase in up to 60% and associated hyperbilirubinaemia (≤grade 2) in 25% of courses and therefore is of no clinical significance. Severe grades of DILI with HD-MTX (grade ≥4) are extremely rare. We describe an adolescent with Burkitt leukaemia who had reversible grade 4 DILI including hyperbilirubinaemia postfirst course of HD-MTX. Rechallenge with two-third dose of HD-MTX in subsequent chemotherapeutic cycle did not cause recurrence of DILI.


Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Burkitt Lymphoma/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Hyperbilirubinemia/chemically induced , Methotrexate/adverse effects , Antimetabolites, Antineoplastic/administration & dosage , Child , Dose-Response Relationship, Drug , Humans , Male , Methotrexate/administration & dosage , Severity of Illness Index
4.
Int J Infect Dis ; 103: 549-551, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-974113

ABSTRACT

Type 2 leprosy reaction (T2LR), or Erythema Nodosum Leprosum (ENL), often poses a therapeutic challenge to clinicians and commonly requires long courses of steroids for control. While immunosuppressants are known to achieve control and lower steroid dependence in T2LR, the prospect of managing a severe T2LR in conjunction with COVID-19, with the concern of worsening COVID-19 with long-term immunosuppression has not previously been encountered. We report a case of severe T2LR treated with oral steroids and methotrexate, with COVID-19 infection acquired during hospital stay, and a favourable outcome achieved despite the continued use of immunosuppressants. We discuss the possible reasons for this both in terms of the drug pharmacodynamics and the immunological profile of T2LR.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , COVID-19/drug therapy , Erythema Nodosum/drug therapy , Immunosuppressive Agents/therapeutic use , Leprosy, Lepromatous/drug therapy , Methotrexate/administration & dosage , SARS-CoV-2 , Adult , COVID-19/immunology , Erythema Nodosum/immunology , Humans , Leprosy, Lepromatous/immunology , Male
5.
Reumatismo ; 72(3): 173-177, 2020 Nov 19.
Article in English | MEDLINE | ID: covidwho-937593

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19) has involved more than 159 countries and more than 5 million people worldwide. A 40-year-old man with a history of rheumatoid arthritis treated with prednisolone, Disease-Modifying Anti-Rheumatic Drugs (DMARDs), and biologic agents was admitted with chief complaints of fever, chills, malaise, myalgia, and dyspnea. Chest computed tomography showed bilateral subsegmental atelectasis and diffuse ground-glass opacities in both lungs inducing the suspicion of COVID-19 infection. The oro-nasopharynx swab sample for COVID-19 polymerase chain reaction was positive. In addition to supportive care, lopinavir/ritonavir 400/100 mg twice daily and oseltamivir (75 mg) twice daily were started in combination with a starting dose of hydroxychloroquine (400 mg). The methotrexate dose was decreased, and the dose of prednisolone was increased to 30 mg for 10 days. Azathioprine and adalimumab were continued at previous doses. The use of biologic agents and DMARDs in rheumatic patients is a serious challenge in the COVID-19 pandemic. In conclusion, during the COVID-19 pandemic, due to the key roles of cytokines in the promotion of the disease, the rheumatic patients may benefit from continuing their previous treatment, which may have protective effects.


Subject(s)
Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adalimumab/administration & dosage , Adult , Antiviral Agents/administration & dosage , Arthritis, Rheumatoid/complications , Azathioprine/administration & dosage , Biological Therapy , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/methods , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Drug Combinations , Drug Therapy, Combination/methods , Humans , Lopinavir/administration & dosage , Male , Methotrexate/administration & dosage , Oseltamivir/administration & dosage , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Prednisolone/administration & dosage , Ritonavir/administration & dosage , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL