BackgroundDepression, and its improvement with disease modifying anti-rheumatic drugs (DMARDs) is understudied in psoriatic arthritis (PsA).ObjectivesTo determine the effectiveness of DMARDs on depression in PsA patients.MethodsPatients enrolled from January 2000 to May 2020 in a large PsA cohort were included. Depression was defined as medical outcomes study short form-36 (SF-36) mental component summary score (MCS) ≤ 40 or mental health (MH) subscale score ≤ 56. Primary outcome was resolution of depression within 1 year of DMARDs, defined by two definitions: 1) MCS > 40 and/or MH subscale score of > 56; 2) Increase in MCS by 2.5 and MH subscale score by 5, the minimal clinically important difference (MCID). Baseline medications [non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional or targeted (c/t) DMARDs] were recorded for all patients and stratified into 3 mutually exclusive ordinal categories: I-No treatment/NSAIDs; II-cDMARDs±NSAIDs without tDMARDs; III-tDMARDs±cDMARDs/NSAIDs. Univariable and multivariable logistic regression models were created to determine the association between medications and resolution of depression, after controlling for age, sex, disease duration and baseline MCS/MH subscale score.ResultsBased on the MCS and MH subscale score definitions, 608 (48%) and 655 (52%) of the 1270 patients, respectively were depressed at baseline. 374 (50.8% males) and 399 (52.4% males) patients were followed up in the groups defined by MCS and MH subscales, respectively for 1 year. Patients in both groups had comparable body mass indices, baseline psoriasis area and severity index and active joint count. Mean MCS and MH subscale scores (standard deviation) were 33.2 (5.2) and 46.0 (10.2). A mean of 11.9 and 11.7 months was noted for resolution of depression in the MCS based analysis and MH subscale-based analysis groups, respectively. More patients achieved resolution of depression based on definition 2 (MCS, 64.7%; MH, 62.2%) as compared to definition 1 (MCS, 54.5%; MH, 53.9). The proportion of patients on each category of medications in both models is shown in the Figure 1. Table 1 depicts the univariate and multivariable regression results by both the definitions of primary outcome in the MH subscales model. The global p-value for medication categories showed a trend towards significance in both models using definition 2. There was a trend towards higher likelihood of response when comparing patients in treatment category III vs category I. A significant response was noted when comparing patients in category III with category II as reference (OR 1.71; 95% CI 1.05-2.76; p 0.03). No significant effect of treatment category on depression was noted using definition 1.Table 1.Association between treatment and resolution of depression in the MH Subscale model (n = 399)VariableResolution by MCIDResolution by MH subscale reductionUnivariable modelMultivariable modelUnivariate modelMultivariate modelOR (95% CI)p valueOR (95% CI)p valueOR (95% CI)p valueOR (95% CI)p valueMale vs. Female0.81 (0.54–1.22)0.310.83 (0.5–1.26)0.391.02 (0.68–1.51)0.940.94 (0.63 –1.42)0.79Baseline age1.01 (1.00 –1.03)0.091.01 (1.00 –1.03)0.161.02 (1.00–1.03)0.051.01 (0.99 –1.03)0.30Baseline PsA duration1.02 (1.00 –1.04)0.121.01 (0.99 –1.03)0.371.02 (1.00– 1.04)0.071.01 (0.99 –1.03)0.22Baseline MH subscale score0.98 (0.96 –1.00)0.030.98 (0.95 –1.00)0.021.04 (1.02– 1.06)<0.00011.04 (1.02 –1.06)<0.0001Medication category0.07*0.09*0.20*0.20* IReference II0.81 (0.48 –1.36)0.420.83 (0.48 –1.41)0.481.09 (0.65– 1.82)0.751.12 (0.66 –1.91)0.67 III1.40 (0.84 –2.36)0.201.41 (0.83 –2.38)0.201.51 (0.92– 2.49)0.101.55 (0.92 –2.59)0.10*global p valueFigure 1.Patients in each drug category.ConclusionIn an observational setting, resolution of depression occurs in majority of patients with PsA within 1 year. Patients on t-DMARDs may experience better improvement in depression compared to other treatments. Future effectiveness studies warrant better definitions of depression and treatment response.AcknowledgementsAJM was supported by the National Psoriasis Foundation Fellowship grant.Disclosure of InterestsAshish Jacob Mathew Speakers bureau: Novartis, IPCA Laboratories, Grant/research support from: Novartis, IPCA Laboratories, Mitchell Sutton: None declared, Daniel Pereira: None declared, Dafna D Gladman Consultant of: AstraZeneca, Grant/research support from: AbbVie, Vinod Chandran Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen and Eli-Lilly
BackgroundThe impact of immunosuppressants on COVID-19 vaccination response and durability in patients with immune-mediated inflammatory diseases (IMID) is yet to be fully characterized. Humoral response may be attenuated in these patients especially those on B cell depleting therapy and higher doses of corticosteroids, but data regarding other immunosuppressants are scarce.ObjectivesWe aimed to investigate antibody and T cell responses and durability to SARS-CoV-2 mRNA vaccines (BNT162b and/or mRNA 1273) in IMID patients on immunomodulatory maintenance therapy other than B-cell depleting therapy and corticosteroids.MethodsThis prospective observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with IMIDs (psoriatic arthritis, psoriasis, inflammatory bowel disease and rheumatoid arthritis) with or without maintenance immunosuppressive therapies (anti-TNF, methotrexate/azathioprine [MTX/AZA], anti-TNF + MTX/AZA, anti IL12/23, anti-IL-17, anti-IL23) compared to healthy controls. Automated ELISA for IgGs to spike trimer, spike receptor binding domain (RBD) and the nucleocapsid (NP) and T-cell release of 9 cytokines (IFNg, IL2, IL4, IL17A, TNF) and cytotoxic molecules (sFasL, GzmA, GzmB, Perforinin) in cell culture supernatants following stimulation with spike or NP peptide arrays were conducted at 4 time points: T1=pre vaccination, T2=median 26 days after dose 1, T3=median 16 days after dose 2 and T4=median 106 days after dose 2. Neutralization assays against four SARS-CoV-2 variants (wild type, delta, beta and gamma) were conducted at T3.ResultsWe followed 150 subjects: 26 healthy controls and 124 IMID patients: 9 untreated, 44 on anti-TNF, 16 on anti-TNF with MTX/AZA, 10 on anti-IL23, 28 on anti-IL12/23, 9 on anti-IL17, 8 on MTX/AZA (Table 1). Most patients mounted antibody and T cell responses with increases from dose 1 to dose 2 (100% seroconversion at T3) and some decline by T4, with variability within groups. Antibody levels and neutralization efficacy was lower in anti-TNFgroups (anti-TNF, anti-TNF + MTX/AZA) compared to controls and waned by T4 (Figure 1). T cell responses were not consistently different between groups. Pooled data showed a higher antibody response to mRNA-1273 compared to BNT162b.Table 1.Baseline characteristics of study participantsControluntreated IMIDAnti- TNFAnti- TNF +MTX/AZAAnti-IL-23Anti -IL-12/23Anti -IL-17MTX/AZAn=26n=9n=44n=16n=10n=28n=9n=8p-valueIMID*N/A IBD9301002704 Psoriasis1318122 PA0732172 AS0830010 RA1100011Age median years [IQR]36 [26-46]33 [27-41]38 [30-51]53 [44-59]48 [45-61]34 [28-47]49 [46-61]42 [31-55]<0.001^Sex male (%)16 (62)5 (56)18 (41)8 (50)5 (50)13 (46)6 (67)4 (50)0.772~BMImedian kg/m2 [IQR]25 [23-28]26 [22-27]22 [24-26]26 [24-28]27 [24-35]22 [21-24]32 [26-34]26[25-33]0.001^Vaccine interval median days [IQR]74 [35-84]54 [31-64]60 [45-69]64 [50-72]74 [35-84]62 [49-69]65 [52-75]58 [21-97]0.372^*multiple IMIDs per patient possibleFigure 1.Antibody responses (A) Anti spike and anti RBD IgG levels at indicated time points. Blue line represents median ratio in convalescent patients. The red line is the seropositivity threshold: the median antibody level of those that pass both a 1% false positive rate and show ≥3SD from the log means of the negative controls. (B) Relative ratio of RBD, spike and NP across time. Black and gray lines indicate median and mean values, respectively. *p≤0.05, **p≤0.01, ***p≤0.001, ****p≤0.0001ConclusionFollowing 2 doses of mRNA vaccination there is 100% seroconversion in IMID patients on maintenance therapy. Antibody levels and neutralization efficacy in anti-TNF group are lower than controls, and wane substantially by 3 months after dose 2. These findings highlight the need for third dose in patients undergoing treatment with anti-TNF therapy and continued monitoring of immunity in these patient groups, taking into consideration newer variants and additional vaccine doses.AcknowledgementsThis work was funded by a donation from Juan and Stefania Speck and by grants VR-1 172711, VS1-175545, FDN-143250, GA1- 177703 and GA2- 177716, from Canadian Institutes of Health Research and COVID Immunity task force and by Sinai Health FoundationDisclosure of InterestsNaomi Finkelstein: None declared, Roya M. Dayam: None declared, Jaclyn Law: None declared, Rogier Goetgebuer: None declared, Gary Chao: None declared, Kento T. Abe: None declared, Mitchell Sutton: None declared, Joanne M. Stempak: None declared, Daniel Pereira: None declared, David Croitoru: None declared, Lily Acheampong: None declared, Saima Rizwan: None declared, Klaudia Rymaszewski: None declared, Raquel Milgrom: None declared, Darshini Ganatra: None declared, Nathalia V. Batista: None declared, Melanie Girard: None declared, Irene Lau: None declared, Ryan Law: None declared, Michelle Cheung: None declared, Bhavisha Rathod: None declared, Julia Kitaygorodsky: None declared, Reuben Samson: None declared, Queenie Hu: None declared, Nigil Haroon: None declared, Robert Inman Consultant of: AbbVie, Janssen, Lilly, Novartis., Grant/research support from: AbbVie, Novartis, Vincent Piguet Consultant of: AbbVie, Almirall, Celgene, Janssen, Kyowa Kirin Co. Ltd, LEO Pharma,Novartis, Pfizer, Sanofi, UCB, and Union Therapeutic, Grant/research support from: Unrestricted educational grants from AbbVie, Bausch Health, Celgene, Janssen, LEO Pharma, Lilly, L’Oréal, NAOS, Novartis, Pfizer, Pierre-Fabre, Sandoz, and Sanofi, Mark Silverberg Speakers bureau: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Consultant of: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Grant/research support from: AbbVie, Janssen, Takeda, Pfizer, Gilead and Amgen, Anne-Claude Grigras: None declared, Tania H. Watts: None declared, Vinod Chandran Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Eli-Lilly.
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