Conventional Synthetic Disease-modifying Antirheumatic Drugs Research Articles

Establishment and verification of a nomogram and a preliminary study on predicting the clinical response of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is an autoinflammatory disease, its core treatment principle is to achieve remission as soon as possible. There is no good prediction model that can accurately predict the remission rate of patients to choose a good treatment scheme. Here, we aimed to verify the prognostic value of some inflammatory indicators in RA and establish a prediction model to predict the remission rate after treatment. A total of 223 patients were enrolled at Qilu Hospital from June 2014 to June 2020. Baseline clinical data were collected and plasma was obtained to detect the inflammatory indicators. All patients were treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). All patients were followed up and were recorded the time to reach the disease activity score-28 with erythrocyte sedimentation rate (DAS28-ESR) of <2.6. A total of 156 patients were randomly assigned to the development cohort, and 67 patients were assigned to the validation cohort. Inflammatory indicators in plasma were detected by enzyme-linked immunosorbent assay (ELISA). The predictive factors were screeded by using least absolute shrinkage and selection operator (LASSO) and Cox regression. The model was created and verified by using the standard method. A total of 6 independent risk factors were analyzed to construct a nomogram to predict the remission rate in 3, 6 and 12 months. The remission rates after treatment in 3, 6 and 12 months were 38.76%, 58.91%, and 81.40%, respectively. Patient age, C-reactive protein (CRP), interleukin (IL)-6, galectin-9 (Gal-9), health assessment questionnaire (HAQ), and DAS28-ESR were included in the prognostic model to predict the remission rate. The resulting model had good discrimination ability in both the development cohort (C-index, 0.729) and the validation cohort (C-index, 0.710). Time-dependent receiver operating characteristic (ROC) curve, calibration analysis, and decision curve analysis (DCA) showed that the model has significant discriminant power and clinical practicability in predicting the remission rate. We established a new predictive model and validated it. The model can predict the remission rate in 3, 6 and 12 months after receiving csDMARDs treatment. By using this model, we can facilitate the identification of high-risk patients early and intervene with them as soon as possible.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING)

BackgroundStudies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. MethodsA national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. Findings4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53–65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5–0.8) and 0.7 (0.6–0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2–2.0) and 1.4 (1.2–1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1–2), 1.2 (1.1–1.4) and 1.5 (1.2–1.8) for prednisolone ≤7.5 mg respectively]. InterpretationThere was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Late-onset rheumatoid arthritis has a similar time to remission as younger-onset rheumatoid arthritis: results from the Ontario Best Practices Research Initiative

BackgroundThe prevalence of rheumatoid arthritis (RA) in persons 60 years or older is estimated to be 2%. Late-onset rheumatoid arthritis (LORA) is traditionally defined as the onset of RA after the age of 60 years. Compared to younger-onset rheumatoid arthritis (YORA) which occurs before the age of 60 years, LORA has unique characteristics and disease manifestations. To date, few reports have addressed LORA and the prognosis of LORA patients remains unclear. We compared the clinical characteristics, time to remission and treatment regimen at remission between LORA and YORA patients.MethodsThis prospective cohort study used a registry database in Ontario, Canada from 2008 to 2020. Patients were included if they had active rheumatoid arthritis (RA) disease (≥1 swollen joint) and were enrolled within 1 year of diagnosis. LORA was defined as a diagnosis of RA in persons 60 years and older and YORA as a diagnosis of RA in persons under the age of 60. Remission was defined by Disease Activity Score 28 (DAS28) ≤2.6. A multivariable Cox proportional hazards model was used to estimate time to remission.ResultsThe study included 354 LORA patients and 518 YORA patients. The mean (standard deviation) baseline DAS28 score was 5.0 (1.3) and 4.8 (1.2) in LORA and YORA patients, respectively (p=0.0946). Compared to YORA patients, the hazard ratio for remission in LORA patients was 1.10 (95% confidence interval 0.90 to 1.34 p=0.36) after adjusting for other prognostic factors. For patients who reached remission, LORA patients were less likely to be on a biologic or Janus kinase (JAK) inhibitor (16% vs. 27%) and more likely to be on a single conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) (34% vs. 27%) than YORA patients (p=0.0039).ConclusionLORA and YORA patients had similar prognosis in terms of time to remission. At remission, LORA patients were more likely to be on a single csDMARD without a biologic or JAK inhibitor.

Cancers and cardiovascular diseases in patients with seropositive rheumatoid arthritis treated with JAK inhibitors, biologics and conventional synthetic DMARDs.

Janus kinase inhibitors and biologics (JAKi/biologics) are cornerstone treatments for rheumatoid arthritis (RA). We evaluated the risks of cancers and cardiovascular diseases (CVDs) in patients with seropositive RA (SPRA) treated with JAKi/biologics. Patients with new-onset SPRA during 2010-2020 in the national healthcare database were identified. Events of overall and site-specific cancers, as well as CVD outcomes, including deep vein thrombosis, pulmonary embolism, and composite cardiovascular events, were investigated. The relative risk of cancers and CVDs compared to conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) users was compared by evaluating the incidence rate ratios (IRRs). Time-dependent Cox analyses were performed to evaluate the relationship between JAKi/biologics usage and patient outcomes. A total of 101,816 and 96,220 patients with SPRA were analysed for cancers and CVD outcomes, respectively. Compared with patients treated only with csDMARDs, the IRRs of overall cancers and CVDs in patients administered JAKi/biologics were 0.88 (95% confidence interval [CI] 0.86-0.89) and 0.91 (95% CI 0.90-0.92), respectively. Site-specific lung, liver, prostate, and skin cancers were more frequent in JAKi/biologics users; JAKi did not confer a greater risk of overall CVDs and cancers compared with other biologics and csDMARDs. JAKi/biologics usage was not accounted for overall cancers and CVDs in adjusted Cox analyses. The incidence of overall cancer and CVD were not increased in patients with SPRA treated with JAKi/biologics and was relatively lower than csDMARD only users, underscoring optimal disease control for risk mitigation. The higher incidence of several site-specific cancers requires further investigation.

Methotrexate, leflunomide and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease.

To examine the association between MTX, LEF and tacrolimus use and the progression of RA-associated interstitial lung disease (ILD). The Korean RA-ILD cohort prospectively enrolled patients with RA-associated ILD at multiple centres from 2015 to 2018 and followed up with them for 3 years. ILD progression was defined by any of the followings: a decrease of ≥10% in forced vital capacity, a decrease of ≥15% in the diffusing capacity of the lung for carbon monoxide, or death from respiratory failure. Of 143 patients, 64 patients experienced ILD progression during a median follow-up period of 33 months. The use of MTX [adjusted hazard ratio (aHR), 1.06; 95% CI, 0.59, 1.89], LEF (aHR, 1.75; 95% CI, 0.88, 3.46) and tacrolimus (aHR, 0.94; 95% CI, 0.52, 1.72) did not increase the risk of ILD progression. However, the association between LEF use and the risk of ILD progression was significant in subgroups with poor lung function (aHR, 8.42; 95% CI, 2.61, 27.15). Older age, male sex, a shorter RA duration, higher RA disease activity and extensive disease at baseline were independently associated with ILD progression. None of the three treatments increased the risk of RA-associated ILD progression, except for LEF, which increased the risk of ILD progression in patients with severe ILD. The appropriate use of conventional synthetic disease-modifying antirheumatic drugs considering RA disease activity and ILD severity would be important for the management of RA-associated ILD.

Multidisciplinary Rheuma-Derma Clinics: 5 Years of Experience at the San Marco Hospital in Catania.

Early psoriatic arthritis (PsA) diagnosis is critical to prescribe timely treatment to prevent the irreversible joint damage and the many other problems that patients with PsA experience. This retrospective study aimed to highlight the benefits of a Rheuma-Derma Clinic focused on the early diagnosis and prompt treatment of PsA with a shared approach among Italian psoriasis patients. Diagnosing PsA early is the main goal to reduce joint damage and disability in the patients affected. Studies describing the results of rheuma-derma clinics aimed to reach this goal emerged in the last decade. This study presents limitations and advantages typical of retrospective designs. A Rheuma-Derma Clinic was created in 2017 at the Rheumatology Department of the Hospital Policlinico Gaspare Rodolico of the University of Catania in San Marco, Italy. This study compared the number of patients under disease-modifying antirheumatic treatment 5years before and after the joint clinic was created. A rheumatologist and dermatologist simultaneously assessed patients with psoriasis and/or PsA to obtain a rapid multidisciplinary diagnostic approach and a shared therapeutic strategy. In addition, demographic, clinical, and clinimetrics data were collected. The number of patients with PsA receiving biological disease-modifying antirheumatic drugs increased 47% (from 255 to 374 patients) before and after the joint clinic was implemented. Likewise, those receiving conventional synthetic disease-modifying antirheumatic drugs increased by 47% (from 367 to 539) as well. Additionally, for all the clinimetrics evaluated (DAS28, HAQ, BASDAI, DAPSA, PASI, PGA), there was an improvement over the 12months under the Rheuma-Derma Clinic care. The measures that improved the most were DAPSA, PGA, PASI, and BASDAI. The implementation of the Rheuma-Derma Clinic was associated with an increase in the number of patients diagnosed, the number of patients with PsA receiving DMARD treatments, and improvements in clinimetrics among the study participants.

Infection profile of immune-modulatory drugs used in autoimmune diseases: analysis of summary of product characteristic data

ObjectiveSerious infection remains a concern when prescribing immune-modulatory drugs for immune-mediated inflammatory diseases. The ‘summary of product characteristics’ (SmPCs) provide information on adverse events for example, infections, from clinical trials...

Risk of pre-eclampsia and impact of disease activity and antirheumatic treatment in women with rheumatoid arthritis, axial spondylarthritis and psoriatic arthritis: a collaborative matched cohort study from Sweden and Denmark.

To explore the risk of pre-eclampsia in rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA) and psoriatic arthritis (PsA), focusing on the impact of treatment and disease activity. We identified RA, AxSpA and PsA singleton pregnancies (2006-2018) by linking medical birth registers to Swedish (SRQ) and Danish (DANBIO) rheumatology registers. Control pregnancies from the medical birth registers were matched 1:10 on maternal age, parity and birth year.We obtained information on antirheumatic treatment before and during pregnancy and disease activity during pregnancy. Risks of pre-eclampsia in RA, AxSpA and PsA pregnancies, compared with control pregnancies, were estimated overall and by antirheumatic treatment (conventional synthetic disease-modifying antirheumatic drug (DMARD)/biological DMARD/corticosteroids, as monotherapy or combination therapy) and disease load (Health Assessment Questionnaire≥1/C-reactive protein≥10/Disease Activity Score in 28 joints≥3.2) through logistic regression (adjusted ORs (aORs) with 95% CI). We observed 69, 34, and 26 pre-eclampsia events among RA (n=1739), AxSpA (n=819) and PsA (n=489), resulting in a risk of pre-eclampsia of, respectively, aOR 1.27 (95% CI 0.96 to 1.67), 1.17 (0.76 to 1.78) and 1.85 (1.10 to 3.12), compared with controls.For RA, maternal combination therapy before and during pregnancy was associated with increased risk (1.59; 1.07 to 2.37 and 1.53; 0.97 to 2.39, respectively). For PsA, maternal monotherapy before pregnancy was associated with pre-eclampsia (2.72; 1.4 to 5.13). In RA pregnancies with available information (43%), high disease load was associated with doubled risk of pre-eclampsia (aOR 1.96; 1.26 to 3.04). PsA pregnancies, but not AxSpA pregnancies, were at increased risk of pre-eclampsia. For RA, combination therapy (potentially a surrogate for high disease activity both before and during pregnancy) and high disease load during pregnancy might be a risk factor for pre-eclampsia.

Adult-Onset Still's Disease-A Complex Disease, a Challenging Treatment.

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with an unknown cause characterized by high-spiking fever, lymphadenopathy, hepatosplenomegaly, hyperferritinemia, and leukocytosis. The clinical course can be divided into three significant patterns, each with a different prognosis: Self-limited or monophasic, intermittent or polycyclic systemic, and chronic articular. Two criteria sets have been validated. The Yamaguchi criteria are the most generally used, although the Fautrel criteria offer the benefit of adding ferritin and glycosylated ferritin values. AOSD's pathogenesis is not yet completely understood. Chemokines and pro-inflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor α (TNFα), interleukin (IL)-1, IL-6, IL-8, and IL-18, play a crucial role in the progression of illness, resulting in the development of innovative targeted therapeutics. There are no treatment guidelines for AOSD due to its rarity, absence of controlled research, and lack of a standard definition for remission and therapy objectives. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CS), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are used in AOSD treatment. Biological therapy, including IL-1, IL-6, IL-18, and IL-17 inhibitors, as well as TNFα or Janus-kinases (JAKs) inhibitors, is administered to patients who do not react to CS and csDMARDs or achieve an inadequate response.

Attitudes and practices in the laboratory monitoring of conventional synthetic disease modifying anti-rheumatic drugs by rheumatologists and rheumatology trainees

ObjectivesThere is scant research about laboratory monitoring in people taking conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for rheumatic disease. Our objective was to conduct a scoping study to assess the range of current attitudes and the variation in practice of laboratory monitoring of csDMARDs by rheumatologists and trainees.MethodsAustralian and overseas rheumatologists or trainees were invited through newsletter, Twitter and personal e-mail, to complete an anonymous online survey between 1 February and 22 March 2021. Questions focused on laboratory tests requested by csDMARD prescribed, frequency/pattern of monitoring, influence of additional factors and combination therapy, actions in response to abnormal tests, and attitudes to monitoring frequencies. Results were presented descriptively and analysed using linear and logistic regression.ResultsThere were 221 valid responses. Most respondents were from Australia (n = 53, 35%) followed by the US (n = 39, 26%), with a slight preponderance of women (n = 84, 56%), ≥ 11 years in rheumatology practice (n = 83, 56%) and in mostly public practice (n = 79, 53%). Respondents had a wide variation in the frequency and scheduling of tests. In general, respondents reported increasing monitoring frequency if patients had numerous comorbidities or if both methotrexate and leflunomide were being taken concurrently. There was a wide variety of responses to abnormal monitoring results and 27 (40%) considered that in general, monitoring tests are performed too frequently.ConclusionsThe results demonstrated a wide variation in the frequency of testing, factors that should influence this, and what responses to abnormal test results are appropriate, indicates a likely lack of evidence and the need to define the risks, benefits and costs of different csDMARD monitoring regimens.

Polyarthritis presented in a patient with untreated chronic hepatitis B infection.

Hepatitis B virus (HBV) infection can cause arthritis, but it is rarely reported. In the current report, we present a case of chronic polyarthritis in a patient with untreated HBV infection. A 63-year-old woman suffering from polyarthritis in her fingers visited our institution. She had experienced exacerbations and remissions of polyarthritis for more than 20 years. She had been diagnosed with rheumatoid arthritis and had been treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and nonsteroidal anti-inflammatory drugs by her primary care doctor, but the csDMARDs were discontinued at the request of the patient 10 years before the first visit to our hospital. The blood test showed negative for rheumatoid factor and anticyclic citrullinated peptides antibody but positive for hepatitis B surface antigen. Hepatitis B surface antigen and HBV-Deoxyribo Nucleic Acid (DNA) were increased to 312.6 (IU/ml) and 4.6 (log copies/ml), respectively. Based on the results of abdominal computed tomography and echography, she was diagnosed with liver cirrhosis. Treatment for HBV infection was begun with oral tenofovir at 25 mg/day. The polyarthritis in her fingers gradually disappeared and has not relapsed for 6 months after the initiation of treatment for HBV infection. When polyarthritis is diagnosed, the possibility that chronic HBV infection can be one of the causes of polyarthritis should be considered.

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis.

Abatacept (Orencia) is a drug used to treat patients with rheumatoid arthritis. The agent improves patients' pain and joint inflammation through modulation of a co-stimulatory signal necessary for T cell activation. We aimed to analyse the efficacy and safety of abatacept in the management of rheumatoid arthritis using the Cochrane systematic review. We conducted a systematic search among PubMed, Cochrane central register of controlled trials, Web of Science, and Embase databases from the establishment of these databases to April 2022. The effectiveness and safety of abatacept in treating rheumatoid arthritis were assessed in terms of American College of Rheumatology (ACR) 20/50/70/90 responses, Disease Activity Score-28 for Rheumatoid Arthritis with C-reactive protein (DAS-28-CRP), and adverse events. The Relative Risks (RRs) of relative safety and efficacy and their corresponding 95 confidence intervals (CIs) were used to compute the pooled assessments of the outcomes. We used the review manager software version 5.4 to analyse our data, and the PRISMA checklist 2020 was used to ensure that our work conforms with the specification of meta-analysis. Our study included 13 randomised control trials with a total of 5978 adult patients from different geographic regions and races. Following the combined analysis of these enrolled studies, the RRs for ACR 20/50/70/90 responses were 1.57 [95%CI 1.27, 1.93], 1.84 [95%CI 1.38, 2.44], 2.36 [95%CI 1.60, 3.47], and 2.95 [95%CI 1.88, 4.63], respectively. Such findings suggest that abatacept-treated patients were 1.57, 1.84, 2.36, and 2.95 times more likely to achieve ACR 20/50/70/90 responses, respectively, than those treated with placebo, conventional synthetic disease-modifying antirheumatic drugs, and or other biologic disease-modifying anti-rheumatic drugs. An exclusive comparison of abatacept and other biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) indicated that participants who were treated with abatacept could achieve better ACR responses than those treated with other b/tsDMARDs. Adverse events were less seen in abatacept-treated patients than in those who were given other b/tsDMARDs. This meta-analysis concludes that in adult with rheumatoid arthritis, abatacept can achieve better health outcomes than other biologic drugs.

Complications After Open Reduction and Internal Fixation for Distal Radius Fractures in Patients With and Without Rheumatoid Arthritis

Rheumatoid arthritis (RA) can have severe impact on patients' functional abilities and increase the risk of fragility fractures. Little is known about how patients with RA fare after operative management of distal radius fractures. The purpose of this study was to compare postoperative complications after surgical fixation in patients with RA and controls, hypothesizing that patients with RA would have higher levels of postoperative complications. Patients were identified using Current Procedural Terminology and International Classification of Diseases, Ninth and Tenth Revision, codes for open treatment of distal radius fractures and RA at 3 level 1 trauma centers over a 5-year period (2015-2019). Chart abstraction provided details regarding injuries and treatment. Age- and sex-matched controls were identified in a 2:1 ratio. Postoperative complications were classified according to the Clavien-Dindo-Sink classification system and divided into early (less than 90 days) and late groups. Sixty-four patients (21 with RA and 43 controls) were included. The patients were predominantly women, with a mean age of 62 years and a mean Charlson comorbidity index of 2.1. The RA medications at the time of injury included conventional synthetic disease-modifying antirheumatic drugs (5/21), biologic disease-modifying antirheumatic drugs (5/21), or chronic oral prednisone (6/21). Rheumatoid medications, except hydroxychloroquine, were withheld for 2-3 weeks after surgery. Rheumatoid patients were significantly more likely to sustain a complication compared with the control group, although this was no longer significant on adjusted analysis. Class I complications were the most common. The incidence of early versus late complications was similar between the groups. A high rate of early return to surgery for fixation failure occurred in the RA group compared with none in the control group. Patients with RA undergoing operative management of distal radius fractures are at risk of postoperative complications, particularly fracture fixation failure, necessitating return to the operative room. High levels of pain, stiffness, and mechanical symptoms were noted in the RA group. Prognostic IV.

TOFA-PREDICT study protocol: a stratification trial to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in psoriatic arthritis (PsA)

IntroductionPsoriatic arthritis (PsA) is a chronic, inflammatory, musculoskeletal disease that affects up to 30% of patients with psoriasis. Current challenges in clinical care and research include personalised treatment, understanding the...

Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials.

IntroductionThe Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported outcome tool recommended for the assessment of disease activity in patients with rheumatoid arthritis (RA) in clinical practice. This analysis evaluated the long-term effect of upadacitinib vs. comparators on RAPID3 scores in patients with RA in the phase 3 SELECT clinical trial program.MethodsThis post hoc analysis included data from five randomized controlled trials (RCTs) in patients receiving upadacitinib 15 mg or 30 mg once daily (QD) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The proportions of patients reporting RAPID3 remission (scores ≤ 3) were assessed at week 60. Correlations between absolute scores for RAPID3 and Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and 28-joint Disease Activity Score with C-reactive protein (DAS28[CRP]) at week 60 were assessed using Spearman correlation coefficients.ResultsA total of 3117 patients were included from the SELECT-NEXT, -BEYOND, -MONOTHERAPY, -COMPARE, and -EARLY trials. By week 60, 32–52% of methotrexate-naïve and csDMARD inadequate responder (IR) patients treated with either upadacitinib 15 mg QD or upadacitinib 30 mg QD reported RAPID3 scores consistent with remission. The proportions were slightly lower in the biologic DMARD-IR SELECT-BEYOND population (19–28%). RAPID3 scores highly correlated (Spearman correlation values ≥ 0.58) with CDAI, SDAI, and DAS28(CRP) scores through week 60 (all p < 0.001).ConclusionsUpadacitinib, as monotherapy or in combination with csDMARDs, was associated with patient-reported remission assessed by RAPID3 over 60 weeks across the SELECT RCTs in patients with RA.Trial registrationSELECT-BEYOND (NCT02706847); SELECT-NEXT (NCT02675426); SELECT-MONOTHERAPY (NCT02706951); SELECT-EARLY (NCT02706873); SELECT-COMPARE (NCT02629159).Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00483-4.

Tofacitinib treatment modulates the levels of several inflammation-related plasma proteins in rheumatoid arthritis and baseline levels of soluble biomarkers associate with the treatment response.

The data on the effects of tofacitinib on soluble proteins in patients with rheumatoid arthritis (RA) is currently very limited. We analyzed how tofacitinib treatment and thus inhibition of the Janus kinase-signal transducer and activation of transcription pathway affects the in vivo levels of inflammation-related plasma proteins in RA patients. In this study, 16 patients with active RA [28-joint disease activity score (DAS28) >3.2] despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) started tofacitinib treatment 5 mg twice daily. Levels of 92 inflammation-related plasma proteins were determined by proximity extension assay at baseline and at 3 months. Tofacitinib treatment for 3 months, in csDMARD background, decreased the mean DAS28 from 4.4 to 2.6 (P < 0.001). Marked (>20%) and statistically significant (P < 0.05) changes were found in the levels of 21 proteins, 18 of which decreased and 3 increased. Of these proteins, 17 are directly involved in inflammatory responses or in the cellular response to cytokines. The highest (>50%) decrease was observed for interleukin-6 (IL-6), C-X-C motif chemokine ligand 1, matrix metalloproteinase-1, and AXIN1. Higher baseline levels of IL-6 and lower levels of C-C motif chemokine 11 and Delta and Notch-like epidermal growth factor-related receptors were associated with DAS28 improvement. Our results indicate that tofacitinib downregulates several proinflammatory plasma proteins that may contribute to the clinical efficacy of tofacitinib. In addition, soluble biomarkers may predict the treatment response to tofacitinib.

Safety and immunogenicity of a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases compared with healthy controls

ObjectivesA third COVID-19 vaccination is recommended for immunosuppressed patients. However, data on immunogenicity and safety of a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) are sparse and...

Comparison of Respiratory Complications of COVID-19 among Patients with Rheumatological Conditions Taking Biological Disease-Modifying Anti-Rheumatic Drugs and Conventional Synthetic Disease-Modifying Antirheumatic Drugs

Objective: To compare the respiratory complications of COVID-19 among patients with rheumatological conditions taking bDMARDs and csDMARDs at Pak Emirates Military Hospital Rawalpindi.&#x0D; Study Design: Comparative prospective study.&#x0D; Place and Duration of Study: Pak Emirates Military Hospital, Rawalpindi Pakistan from Mar to May 2020.&#x0D; Methodology: Patients diagnosed with COVID-19 on polymerase chain reaction having previously rheumatological conditions managed either with bDMARD or cs DMARD were included in the study. They were followed up for three weeks after the positive polymerase chain reaction. Complications leading to the use of oxygen or ICU support or death were compared in both groups of patients.&#x0D; Results: A total of 82 patients with any rheumatological condition managed either with bDMARD or csDMARD tested positive for covid-19 on polymerase chain reaction and were included in the final analysis. 30 (36.6%) patients were taking bDMARDs while 52 (63.4%) were taking csDMARD. In addition, 4 (4.8%) low dose oxygen therapy, 5 (6.1%) required moderate dose oxygen therapy, while 5 (6.1%) required severe dose oxygen therapy or intensive care unit support. 2 (2.4%) patients died within the three weeks. The requirement of moderate or severe dose oxygen and intensive care unit support was found statistically significantly more in the group taking csDMARDS.&#x0D; Conclusion: The presence of complications of COVID -19 and the requirement of oxygen and intensive care unit support were present in some of the patients taking DMARDs. Among the DMARDs, bDMARDs were less linked with complications, but large studies with better design required better results.

The effect of tofacitinib on residual pain in patients with rheumatoid arthritis and psoriatic arthritis

ObjectivePost hoc analysis of pooled data from nine randomised controlled trials to assess the effect of tofacitinib (oral Janus kinase inhibitor for treatment of rheumatoid arthritis (RA) and psoriatic arthritis...

Factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy: results from the COVID-19 Global Rheumatology Alliance physician-reported registry

ObjectivesTo investigate factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy (IIM).MethodsDemographic data, clinical characteristics and COVID-19 outcome severity of adults with IIM were obtained from the COVID-19...