IL-6 inhibitors and JAK inhibitors as favourable treatment options for patients with anaemia and rheumatoid arthritis: ANSWER cohort study.

OBJECTIVES: Anaemia, a common comorbidity of RA, is related to high disease activity and poor prognosis. It is unknown which biologic/targeted synthetic (b/ts)-DMARDs are optimal for patients with anaemia and RA in regulating anaemia and controlling disease activity. METHODS: We investigated the change in haemoglobin (Hb) levels, drug retention rates and disease activities after the administration of b/ts-DMARDs with different modes of action [TNF inhibitors (TNFis), immunoglobulin fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), IL-6 receptor inhibitors (IL-6Ris) and Janus kinase inhibitors (JAKis)] in patients with RA stratified by baseline Hb levels using the multicentre observational registry for patients with RA in Japan (ANSWER cohort). RESULTS: A total of 2093 patients with RA were classified into three groups based on tertiles of the baseline Hb levels (Hblow, anaemic; Hbint, intermediate; Hbhigh, non-anaemic). IL-6Ri increased Hb levels in all groups (the mean change at 12 months in Hblow was +1.5 g/dl, Hbint +0.7 g/dl and Hbhigh +0.1 g/dl). JAKis increased the Hb level in patients with anaemia and RA and retained or decreased the Hb level in non-anaemic patients (the mean change at 12 months in Hblow was +0.6 g/dl, Hbint 0 g/dl and Hbhigh -0.3 g/dl). In patients with anaemia and RA, overall adjusted 3-year drug retention rates were higher in JAKi followed by IL-6Ri, CTLA4-Ig and TNFi (78.6%, 67.9%, 61.8% and 50.8%, respectively). Change of disease activity at 12 months was not different among different b/ts-DMARDs treatments. CONCLUSION: IL-6Ri and JAKi can effectively treat patients with anaemia and RA in a real-world setting.

Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.

OBJECTIVES: This multicentre, retrospective study aimed to compare retention and reasons for discontinuation between Janus kinase inhibitors (JAKi) and biologic disease-modifying antirheumatic drugs in patients with elderly-onset rheumatoid arthritis (EORA). METHODS: Patients with RA enrolled in a Japanese multicentre observational registry between 2015 and 2022 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding factors by indication for initiation of tumor necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), cytotoxic T-lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) blockers, or JAKi, a propensity score based on baseline characteristics was used to compare drug retention. To assess the reasons for discontinuation, retention rates for ineffectiveness, adverse events, and remission were analyzed as secondary outcomes. RESULTS: A total of 572 patients with 835 treatment courses were identified (314 TNFi, 175 IL-6i, 228 CTLA4-Ig, and 118 JAKi). After adjusting for differences in baseline characteristics, drug retention was significantly higher for IL-6i (HR = 0.38, 95%CI = 0.27-0.55, p< 0.01) as compared with TNFi. Discontinuation due to lack of effectiveness was lower with the JAKi (HR = 0.38, 95%CI = 0.22-0.66, p< 0.01) and the IL-6i (HR = 0.29, 95%CI = 0.19-0.46, p< 0.01) as compared with the TNFi although the CTLA4-Ig had a similar HR to TNFi. The adjusted incidence of discontinuation due to adverse event was higher in the JAKi (HR = 2.86, 95%CI = 1.46-5.59, p< 0.01) than the TNFi. CONCLUSIONS: In EORA patients, IL-6i and JAKi had longer retention and less discontinuation due to ineffectiveness than TNFi. The potential risks of JAKi should be approached with an individualized perspective.

Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.

OBJECTIVES: To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). METHODS: Retrospective analysis was conducted on data from the ANSWER cohort comprising 3,623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention. RESULTS: Of these, 450 (12.4%) met the first two criteria of EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared to those under 65, HR = 0.46, 95% CI: 0.31 to 0.69), higher rheumatoid factor (RF) titres (HR = 1.005, 95% CI: 1.00 to 1.01), higher clinical disease activity index (HR = 1.02, 95% CI: 1.01 to 1.03), lower methotrexate dosage (HR = 0.97, 95% CI: 0.95 to 0.99), and comorbidities like hypertension (HR = 1.53, 95% CI: 1.2 to 1.95) and diabetes (HR = 1.37, 95% CI: 1.09 to 1.73). Anti-interleukin 6 receptor antibodies (aIL-6R, HR = 0.53, 95% CI: 0.37 to 0.75) and JAKi (HR = 0.64, 95% CI: 0.46 to 0.90) were associated with fewer discontinuations due to ineffectiveness compared to tumour necrosis factor inhibitors. Oral glucocorticoids usage (HR = 1.65, 95% CI: 1.11 to 2.47) was linked to increased discontinuation due to toxic adverse events. CONCLUSION: Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention.

Trends of disease activity in Japanese patients over 75 years with rheumatoid arthritis from 2014 to 2021- the ANSWER cohort study.

OBJECTIVES: To investigate if disease activity among elderly RA patients over 75 years has changed over time in the real-world clinical setting. METHODS: Data from an observational multicentre registry of RA patients in Japan were analyzed. The primary outcome was to evaluate the changes in the proportion of very elderly RA patients (over 75 years) who achieved remission and low disease activity, from 2014 to 2021. The secondary outcome was to identify factors associated with remission and low disease activity by comparing demographic and clinical characteristics among the patients who had a study visit within the study period, using multivariate logistic regression. RESULTS: A total of 32 161 patient visits were identified from 2014 to 2021. The proportion of patients over 75 years increased from 16.5% to 26.9%, with biologics and targeted-synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) usage increasing and glucocorticoids usage decreasing, while conventional-synthetic DMARDs usage remained relatively stable. The proportion of RA patients over 75 years achieving remission and low disease activity significantly increased from 62.2% to 78.2% (p for trend < 0.001). A negative factor associated with achieving remission and low disease activity was glucocorticoid usage, seropositivity, and history of previous b/tsDMARDs use while MTX usage was associated positively, independent of other predictors. CONCLUSIONS: In our cohort, disease activity among very elderly RA patients has improved over time. The study suggests the importance of using a treat-to-target approach in very elderly RA patients to improve clinical outcomes.

Validity of claims-based diagnoses for infectious diseases common among immunocompromised patients in Japan.

BACKGROUND: To validate Japanese claims-based disease-identifying algorithms for herpes zoster (HZ), Mycobacterium tuberculosis (MTB), nontuberculous mycobacteria infections (NTM), and Pneumocystis jirovecii pneumonia (PJP). METHODS: VALIDATE-J, a multicenter, cross-sectional, retrospective study, reviewed the administrative claims data and medical records from two Japanese hospitals. Claims-based algorithms were developed by experts to identify HZ, MTB, NTM, and PJP cases among patients treated 2012-2016. Diagnosis was confirmed with three gold standard definitions; positive predictive values (PPVs) were calculated for prevalent (regardless of baseline disease-free period) and incident (preceded by a 12-month disease-free period for the target conditions) cases. RESULTS: Of patients identified using claims-based algorithms, a random sample of 377 cases was included: HZ (n = 95 [55 incident cases]); MTB (n = 100 [58]); NTM (n = 82 [50]); and PJP (n = 100 [84]). PPVs ranged from 67.4-70.5% (HZ), 67.0-90.0% (MTB), 18.3-63.4% (NTM), and 20.0-45.0% (PJP) for prevalent cases, and 69.1-70.9% (HZ), 58.6-87.9% (MTB), 10.0-56.0% (NTM), and 22.6-51.2% (PJP) for incident cases, across definitions. Adding treatment to the algorithms increased PPVs for HZ, with a small increase observed for prevalent cases of NTM. CONCLUSIONS: VALIDATE-J demonstrated moderate to high PPVs for disease-identifying algorithms for HZ and MTB using Japanese claims data.

Add-on effectiveness of methotrexate or iguratimod in patients with rheumatoid arthritis exhibiting an inadequate response to Janus kinase inhibitors: The ANSWER cohort study.

OBJECTIVES: This multicenter, retrospective study evaluated the effectiveness of add-on methotrexate (MTX) or iguratimod (IGU) in patients with rheumatoid arthritis exhibiting an inadequate response to Janus kinase inhibitors (JAKis). METHODS: Forty-five patients were treated with new additional MTX (n = 22) or IGU (n = 23) and followed for 6 months. Patients' background is as follows: age, 59.2 years; disease activity score of 28 joints with C-reactive protein (DAS28-CRP), 3.4; clinical disease activity index, 15.7; biological disease-modifying antirheumatic drug (DMARD)-switched cases, 77.8%; first JAKi cases, 95.6%; and JAKi treatment: tofacitinib (n = 25), baricitinib (n = 17), upadacitinib (n = 2), and peficitinib (n = 1) for 9.6 months. RESULTS: Thirty-five patients continued the combination therapy for 6 months without a significant change in concomitant glucocorticoid or other conventional synthetic DMARDs. DAS28-CRP (MTX, 3.6 to 2.6, p < 0.05; IGU, 3.3 to 2.1, p < 0.001) and clinical disease activity index (MTX, 16.7 to 8.8, p < 0.05; IGU, 14.6 to 6.5, p < 0.01) improved significantly from baseline. Using the 2019 European League Against Rheumatism criteria, 45.4% (MTX) and 39.1% (IGU) achieved moderate or good response and 40.9% (MTX) and 39.1% (IGU) achieved American College of Rheumatology 20% improvement criteria. CONCLUSIONS: Adding MTX or IGU to inadequate responders of JAKi can be considered as a complementary treatment.

Comparative effectiveness of trimethoprim-sulfamethoxazole versus atovaquone for the prophylaxis of pneumocystis pneumonia in patients with connective tissue diseases receiving prolonged high-dose glucocorticoids.

We compared the prophylactic effect of trimethoprim-sulfamethoxazole (TMP-SMX) with atovaquone for pneumocystis pneumonia (PCP) in patients with connective tissue diseases (CTDs) receiving high-dose glucocorticoids. Patients with CTDs aged ≥ 18 years who were treated with a prolonged course (≥ 4 weeks) of glucocorticoids (≥ 20 mg/day prednisone) in a Japanese tertiary center between 2013 and 2017 were included. The patients were categorized into two groups: TMP-SMX and atovaquone group. Adjusted cumulative incidence of PCP was compared between the two groups after propensity score weighting for differences in confounding factors. A total of 480 patients with a prolonged high-dose glucocorticoid treatment were identified. Out of 383 patients with TMP-SMX prophylaxis, 102 (26.8%) patients experienced adverse events leading to discontinuation within 4 weeks of initiation, while no patient in the atovaquone discontinued the therapy. Two hundred eighty-one patients received TMP-SMX, while 107 received atovaquone for PCP prophylaxis. During a total of 397.0 person-years, 7 PCP cases (2 in the TMP-SMX, 5 in the atovaquone) occurred with a mortality rate of 54.5%. After adjusting for differences in baseline characteristics, the adjusted cumulative incidence of PCP was similar between the two group (HR 0.97, 95% CI 0.19-5.09, p = 0.97). Prophylactic effects for PCP in CTDs patients receiving prolonged high-dose glucocorticoids were similar between TMP-SMX and atovaquone. Atovaquone was well-tolerated with no side effects.

Validity of claims-based algorithms for selected cancers in Japan: Results from the VALIDATE-J study.

PURPOSE: Real-world data from large administrative claims databases in Japan have recently become available, but limited evidence exists to support their validity. VALIDATE-J validated claims-based algorithms for selected cancers in Japan. METHODS: VALIDATE-J was a multicenter, cross-sectional, retrospective study. Disease-identifying algorithms were used to identify cancers diagnosed between January or March 2012 and December 2016 using claims data from two hospitals in Japan. Positive predictive values (PPVs), specificity, and sensitivity were calculated for prevalent (regardless of baseline cancer-free period) and incident (12-month cancer-free period; with claims and registry periods in the same month) cases, using hospital cancer registry data as gold standard. RESULTS: 22 108 cancers were identified in the hospital claims databases. PPVs (number of registry cases) for prevalent/incident cases were: any malignancy 79.0% (25 934)/73.1% (18 119); colorectal 84.4% (3519)/65.6% (2340); gastric 87.4% (3534)/76.8% (2279); lung 88.1% (2066)/79.9% (1636); breast 86.4% (4959)/59.9% (3185); pancreatic 87.1% (582)/80.4% (508); melanoma 48.7% (46)/42.9% (36); and lymphoma 83.6% (1457)/77.8% (1035). Specificity ranged from 98.3% to 100% (prevalent)/99.5% to 100% (incident); sensitivity ranged from 39.1% to 67.6% (prevalent)/12.5% to 31.4% (incident). PPVs of claims-based algorithms for several cancers in patients ≥66 years of age were slightly higher than those in a US Medicare population. CONCLUSIONS: VALIDATE-J demonstrated high specificity and modest-to-moderate sensitivity for claims-based algorithms of most malignancies using Japanese claims data. Use of claims-based algorithms will enable identification of patient populations from claims databases, while avoiding direct patient identification. Further research is needed to confirm the generalizability of our results and applicability to specific subgroups of patient populations.

Comparison of efficacy between anti-IL-6 receptor antibody and other biological disease-modifying antirheumatic drugs in the patients with rheumatoid arthritis who have knee joint involvement: the ANSWER cohort, retrospective study.

OBJECTIVE: We aimed to investigate the efficacy of anti-IL-6 receptor antibody (aIL-6) and other biologic disease-modifying antirheumatic drugs (bDMARDs), such as TNF inhibitor and CTLA4-Ig in the treatment of rheumatoid arthritis (RA) in patients with knee joint involvement. METHODS: We retrospectively analyzed 1059 treatment courses of patients with RA who visited our hospitals and were treated with bDMARDs. We categorized them into two groups, with or without knee joint involvement. We investigated the clinical disease activity index (CDAI) at baseline and 12 weeks after the initiation of bDMARDs. We compared the improvement of the markers between aIL-6 and other bDMARDs. RESULTS: Treatment with aIL-6 significantly increased ΔCDAI (n = 91, 15.4 ± 1.1; mean ± SEM) in patients with knee joint involvement, compared to other bDMARDs (n = 232, 11.0 ± 0.7) at 12 weeks (P = 0.006). Following the multivariate analysis adjusted by the CDAI levels at baseline, age, gender, concomitant use of methotrexate, and the first use of bDMARDs, ΔCDAI levels were significantly higher in aIL-6, compared to other bDMARDs (P = 0.02). However, there was no significant difference in ΔCDAI improvement between aIL-6 (n = 162, 5.9 ± 0.6) and other bDMARDs (n = 573, 6.2 ± 0.4) in patients without swollen knee joints. ΔCDAI levels were equally increased in patients with shoulder and elbow joint involvement. CONCLUSION: aIL-6 was more effective in the patients with RA and knee joint involvement, compared to other bDMARDs.

Comparison of the efficacy and safety of biologic agents between elderly-onset and young-onset RA patients: the ANSWER cohort study.

The objective of the study was to compare the efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) between elderly-onset rheumatoid arthritis (EORA) and young-onset rheumatoid arthritis (YORA) patients. Patients with rheumatoid arthritis (RA) aged ≧18 years enrolled in a Japanese multicenter observational registry between 2009 and 2018 who had moderate or high disease activity when initiating bDMARDs were included. EORA was defined as RA with onset at 60 or over. After propensity score weighting for differences in confounding factors, generalized estimating equations were used to assess the relationship between the age of RA onset and bDMARD clinical effectiveness at 48 weeks after starting a bDMARD. Among a total of 7183 patients in the registry, 2815 (39.2%) were identified as EORA. The proportion of patients on bDMARDs was lower in the EORA as compared to the YORA (18.3% vs 28.0%, p < 0.001). Of the 989 bDMARD initiators, 364 (36.8%) were identified as EORA. The median follow-up duration was 48 weeks both in the EORA and in the YORA. After adjusting for differences in baseline characteristics between the two age groups, there was no significant difference in Clinical Disease Activity Index scores at 48 weeks (mean difference 1.01, 95% CI = - 0.62 to 2.64, p = 0.22). There was a non-significant trend toward lower remission in EORA (OR = 0.52, 95% CI = 0.24-1.14, p = 0.10), and low disease activity/remission was similar (OR = 0.86, 95% CI = 0.29-2.52, p = 0.77). Drug retention (HR = 0.95, 95% CI = 0.55-1.35, p = 0.78) and discontinuations due to adverse events (HR = 0.78, 95% CI = 0.38-1.18, p = 0.22) were similar between the two age groups after adjustment for confounders. In RA patients initiating bDMARDs, improvements in clinical disease at 48 weeks were similar between EORA and YORA. Drug retention and adverse events discontinuation were similar between the two age groups.

The family history of rheumatoid arthritis in anti-cyclic citrullinated peptide antibody-positive patient is not a predictor of poor clinical presentation and treatment response with modern classification criteria and treatment strategy: the ANSWER cohort study.

A family history of rheumatoid arthritis (RA) is a strong risk factor for developing RA, affecting both genetically and environmentally. However, whether family history provides clinically relevant information in the modern classification and treatment remains largely unknown. This study aimed to determine whether a family history of RA is associated with a different clinical presentation of RA and treatment response. We retrospectively evaluated the demographic data and disease activity of newly diagnosed RA patients at baseline, 1 year, and 2 years after onset, using the ANSWER (Kansai consortium for the well-being of rheumatic disease patients) cohort data. Thirty-one patients (11.9%) among 260 newly diagnosed RA patients had a family history of RA up to second degree. There was no significant difference in the age at onset, time from onset to first visit, sex, positivity or value of rheumatoid factor or anti-cyclic citrullinated peptide antibody (ACPA), or disease activity between patients with and without a family history of RA. However, patients who had a family history of RA and were ACPA positive showed significantly lower erythrocyte sedimentation rate, and C-reactive protein. Disease activity in patients with a family history was not worse at baseline, after 1 year or 2 years of treatment. The Larsen score 2 years after onset was equivalent between the patients with and without a family history of RA in ACPA-positive patients. Family history of RA in ACPA-positive patients is not associated with high disease activity at baseline and is not a predictor of poor outcome 2 years after onset.

Validation of claims-based algorithms for rheumatoid arthritis in Japan: Results from the VALIDATE-J study.

AIM: Validity of Algorithms in Large Databases: Infectious Diseases, Rheumatoid Arthritis, and Tumor Evaluation in Japan (VALIDATE-J) study examined algorithms for identifying rheumatoid arthritis (RA) in Japanese claims data. METHODS: VALIDATE-J was a multicenter, cross-sectional retrospective study. Disease-identifying algorithms were used to detect RA diagnosed between January 2012 and December 2016 using claims data from two Japanese hospitals. An RA diagnosis was confirmed using one of four gold standard definitions. Positive predictive values (PPVs) were calculated for prevalent (regardless of baseline RA-free period) and incident (preceded by a 12-month RA-free period) cases. RESULTS: Of patients identified using claims-based algorithms, a random sample of 389 prevalent and 134 incident cases of RA were included. Cases identified by an RA diagnosis, no diagnosis of psoriasis, and treatment with any disease-modifying antirheumatic drugs (DMARDs) resulted in the highest PPVs versus other claims-based treatment categories (29.0%-88.3% [prevalent] and 41.0%-78.2% [incident]); cases identified by an RA diagnosis, no diagnosis of psoriasis, and glucocorticoid-only treatment had the lowest PPVs. Across claims-based algorithms, PPVs were highest when a physician diagnosis or decision by adjudicators (confirmed and probable cases) was used as the gold standard and were lowest when American College of Rheumatology/European Alliance of Associations for Rheumatology 2010 criteria were applied. PPVs of claims-based algorithms for RA in patients aged ≥66 years were slightly higher versus a USA Medicare population (maximum PPVs of 95.0% and 88.9%, respectively). CONCLUSION: VALIDATE-J demonstrated high PPVs for most claims-based algorithms for diagnosis of prevalent and incident RA using Japanese claims data. These findings will help inform appropriate RA definitions for future claims database research in Japan.

Association of large joint involvement at the start of biological disease-modifying antirheumatic drugs and Janus kinase inhibitors with disease activity and drug retention in patients with rheumatoid arthritis: The ANSWER cohort study.

AIM: To investigate the association of large joint involvement (LJI) with disease activity and drug retention in patients with rheumatoid arthritis (RA) who started receiving a biological disease-modifying antirheumatic drug or Janus kinase inhibitor. METHODS: Patients with RA from a Japanese multicenter observational registry were enrolled. Our definition of large joints included the shoulder, elbow, hip, knee, and ankle joints. Linear mixed-effects models were used to examine changes in the clinical disease activity index (CDAI) score at Week 24 as the primary outcome, and drug retention rates were compared between patients with and without LJI using Cox proportional hazards models. We examined the potential effect modifications of changes in the CDAI by baseline characteristics. RESULTS: Overall, 2507 treatment courses from 1721 patients were included (LJI, 1744; no LJI, 763). Although LJI was associated with significantly higher changes in CDAI from baseline at Week 24 (difference in change in CDAI: -5.84 [-6.65 to -5.03], p < .001), CDAI was significantly higher in patients with LJI over time. Retention rates were similar in both groups. The association of LJI with changes in disease activity was more prominent in patients with a short disease duration, negative anti-citrullinated peptide antibodies, and interleukin-6 receptor inhibitor (IL-6Ri) use. CONCLUSION: Although LJI was associated with a greater reduction in disease activity from baseline, higher disease activity at baseline was not offset over time in patients with LJI, demonstrating that LJI is an unfavorable predictor. An early treat-to-target strategy using an IL-6Ri may be beneficial for patients with LJI.

Predictors of serological failure after treatment in HIV-infected patients with early syphilis in the emerging era of universal antiretroviral therapy use.

BACKGROUND: The optimal treatment of early syphilis (primary, secondary and early latent) in HIV-infected patients remains controversial. The Center for Diseases Control STD Treatment Guidelines recommended 1 dose of benzathine penicillin G (BPG) regardless of HIV infection. However, many providers modify the treatment for early syphilis. METHODS: We performed a retrospective chart review of all cases of early syphilis with positive serologic test results in HIV-infected patients from May 2006 to May 2011 in 2 large, urban HIV clinics. Early syphilis includes primary, secondary, and early latent syphilis. Serological failure was defined as a lack of 4-fold decrease in rapid plasma reagent (RPR) titers 9 to 12 months after syphilis treatment. Patients whose RPR titers decreased after treatment and subsequently increased 4-fold at 9 to 12 months were excluded from the analysis of serological response because of possibility as "reinfection". Baseline characteristics were tested as predictive factors of serological failure using a univariate and multivariate logistic regression model, respectively. RESULTS: Of 560 patients with confirmed cases of early syphilis, 51 (9.0%) experienced serological failure. Multivariate logistic regression modeling demonstrated that the predictive factors associated with serological failure after early syphilis treatment were baseline RPR titer ≤ 1:16 (OR 3.91 [95% CI, 2.04-7.47]), a previous history of syphilis (OR 3.12 [95% CI, 1.55-6.26]), and a CD4 T-cell count below 350 cells/ml (OR 2.41 [95% CI, 1.27-4.56]). Of note, type of syphilis treatment (1 dose versus 3 doses of BPG) did not appear to affect the proportion of serological failure (4% versus 10%, P = 0.29), however the power of this study to detect small differences was limited. CONCLUSIONS: HIV-infected patients with baseline RPR titer ≤1:16, syphilis history, and/or a CD4 T-cell count <350 cells/ml should be closely monitored for serologic failure after early syphilis treatment. This study did not detect a substantial difference between treatment with > 1 dose of BPG and decreased frequency of serological failure, supporting the current recommendation that one dose of BPG is adequate treatment for early syphilis in HIV-infected patients.

Coccidioides thyroiditis in an HIV-infected patient.

We report a case of Coccidioides thyroiditis in an HIV-infected patient with a history of recent Coccidioides pneumonia but with negative Coccidioides serology determined by enzyme immunoassay at presentation. Diagnosis of Coccidioides thyroiditis was made based on histopathologic examination and culture of thyroid abscess material obtained by fine-needle aspiration biopsy.

Pneumonia Due to Drug-Resistant Streptococcus pneumoniae.

Pneumonia is a major infectious disease associated with significant morbidity and mortality, with Streptococcus pneumoniae the predominant pathogen in community-acquired cases, accounting for 20% to 50% of bacterial cases. Although pneumococcal resistance to ß-lactams is now common worldwide, high-dose parental penicillin G, many other parental ß-lactams and some oral ß-lactams continue to be efficacious. The new Clinical and Laboratory Standards Institute susceptibility breakpoints for parental penicillin G for nonmeningeal infections (≤2 µg/mL, susceptible; 4 µg/mL, intermediate; ≥8 µg/mL, resistant) introduced in 2008 facilitate appropriate reporting and use of penicillin G. Pneumococcal vaccine usage in children from 2000 has led to significant decreases in morbidity and mortality due to S. pneumoniae in all age groups, and the increase in resistant serotypes, such as 19A, appears to be decreasing following the introduction of an expanded valence vaccine in 2010. Judicious use of antimicrobial agents is the best long-term approach in order to reduce S. pneumoniae resistance.

Factors affecting drug retention of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study.

This multi-center, retrospective study aimed to clarify the factors affecting drug retention of the Janus kinase inhibitors (JAKi) including baricitinib (BAR) and tofacitinib (TOF) in patients with RA. Patients were as follows; females, 80.6%; age, 60.5 years; DAS28-ESR, 4.3; treated with either BAR (n = 166) or TOF (n = 185); bDMARDs- or JAKi-switched cases (76.6%). The reasons for drug discontinuation were classified into four major categories. The drug retention was evaluated at 24 months using the Kaplan-Meier method and multivariate Cox proportional hazards modelling adjusted by confounders. Discontinuation rates for the corresponding reasons were as follows; ineffectiveness (22.3%), toxic adverse events (13.3%), non-toxic reasons (7.2%) and remission (0.0%). Prior history of anti-interleukin-6 receptor antibody (aIL-6R) ineffectiveness significantly increased the risk of treatment discontinuation due to ineffectiveness (p = 0.020). Aging (≥ 75 years) (p = 0.028), usage of PSL ≥ 5 mg/day (p = 0.017) and female sex (p = 0.041) significantly increased the risk of treatment discontinuation due to toxic adverse events. Factors not associated with treatment discontinuation were: number of prior bDMARDs or JAKi, concomitant MTX usage, difference of JAKi, and prior use of TNF inhibitor, CTLA4-Ig or other JAKi.

Comparison of the drug retention and reasons for discontinuation of tumor necrosis factor inhibitors and interleukin-6 inhibitors in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.

BACKGROUND: This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of either tumor necrosis factor inhibitors (TNFi) or interleukin-6 inhibitors (IL-6i) in patients with elderly-onset rheumatoid arthritis (EORA). METHODS: Patients with rheumatoid arthritis (RA) enrolled in a Japanese multicenter observational registry between 2011 and 2020 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding by indication for treatment with TNFi or IL-6i, a propensity score based on multiple baseline characteristics variables was used to compare the drug retention and causes for discontinuation between TNFi and IL-6i. Adjusted cumulative incidence of drug discontinuation for each reason was compared between the two groups using the Fine-Gray model. RESULTS: Among a total of 9,550 patients in the registry, 674 TNFi and 297 IL-6i initiators with EORA were identified. Age, the proportion of females, disease duration, and baseline disease activity at the time of TNFi or IL-6i initiation were similar between the two groups. After adjusting for differences in baseline characteristics between the two groups, overall drug discontinuation was significantly lower in the IL-6i as compared to the TNFi (HR = 0.71, 95%CI = 0.59-0.86, p < 0.001). The adjusted cumulative incidence of discontinuation due to lack of effectiveness was lower with the IL-6i (HR = 0.46, 95%CI = 0.33-0.63, p < 0.001) while those due to adverse events (HR = 0.82, 95%CI = 0.56-1.18, p = 0.28) or achievement of clinical remission (HR = 1.09, 95%CI = 0.62-1.91, p = 0.76) were similar between the two groups. CONCLUSIONS: In EORA patients initiating a TNFi or IL-6i, significantly higher drug retention was observed with IL-6i. Discontinuation due to lack of effectiveness was significantly less frequent in IL-6i while discontinuations due to adverse event or achievement of clinical remission were similar between the two groups.

Drug retention of sarilumab, baricitinib, and tofacitinib in patients with rheumatoid arthritis: the ANSWER cohort study.

OBJECTIVES: The aim of this multicenter, retrospective study was to clarify the retention rates of sarilumab (SAR), baricitinib (BAR), and tofacitinib (TOF) in patients with rheumatoid arthritis (RA). METHODS: Patients treated with either SAR (n = 62), BAR (n = 166), or TOF (n = 185) (females, 80.9%; age, 61.0 years; disease duration, 11.1 years; rheumatoid factor positivity, 84.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate, 4.3; concomitant prednisolone dose, 5.3 mg/day [47.0%] and methotrexate dose, 8.8 mg/week [58.4%]; biologics- or Janus kinase inhibitors-switched cases 78.4%) were included. The reasons for drug discontinuation were classified into 4 major categories (lack of effectiveness, toxic adverse events, non-toxic reasons, and remission) by each attending physician. The drug retention rate was estimated at 18 months using the Kaplan-Meier method and adjusted for potential confounders by Cox proportional hazards modeling. RESULTS: The discontinuation rates of SAR, BAR, and TOF for the corresponding reasons were as follows, respectively: lack of effectiveness (15.7%, 15.6%, and 21.5%; P = 0.84), toxic adverse events (15.8%, 12.1%, and 12.3%; P = 0.35), non-toxic reasons (10.9%, 7.7%, and 6.8%; P = 0.35), and remission (0.0%, 2.8%, and 0.0%; P = 1.0). The overall retention rates excluding non-toxic reasons and remission were as follows: 68.8% for SAR, 72.5% for BAR, and 66.7% for TOF (P = 0.54). CONCLUSIONS: After adjustment by potent confounders, SAR, BAR, and TOF showed similar discontinuation rates due to lack of effectiveness and toxic adverse events. Key Points • This is the first retrospective multicenter study that aimed to clarify the retention rates and reasons for discontinuation of SAR, BAR, and TOF in patients with RA.