Real-World Treatment and Care Patterns in Patients With Rheumatoid Arthritis Initiating First-Line Tumor Necrosis Factor Inhibitor Therapy in the United States.

OBJECTIVE: Treatment guidelines for rheumatoid arthritis (RA) recommend targeting low disease activity or remission and switching therapies for patients not reaching those targets. We evaluated real-world use of disease activity measures, treatment discontinuation, and switching patterns among patients with RA initiating a first-line tumor necrosis factor inhibitor (TNFi). METHODS: Data from adult patients with RA initiating a first-line TNFi were collected from the American Rheumatology Network (January 2014-August 2021). The proportion of patients with recorded disease activity scores (Clinical Disease Activity Index [CDAI] or Routine Assessment of Patient Index Data 3 [RAPID3]) at TNFi initiation was assessed. Among patients with moderate or severe RA at TNFi initiation, reasons for discontinuation and subsequent advanced therapy were evaluated. RESULTS: Among TNFi initiators (n = 15,182), 44.8% recorded a CDAI/RAPID3 score at treatment initiation; of those who did not, 47.0% had recorded a tender and/or swollen joint count or pain score. Among patients with moderate or severe RA (n = 1,651), 52% discontinued their initial TNFi during follow-up, of which 15%, 46%, 28%, and 12% initiated the same TNFi, another TNFi, a non-TNFi biologic, or a Janus kinase inhibitor, respectively. The proportion of patients restarting the same TNFi or initiating another TNFi varied according to TNFi discontinuation reason. CONCLUSION: In clinical practice, over half of patients with RA initiating a first-line TNFi did not have baseline disease activity assessments. Many patients cycled through TNFi despite citing lack of efficacy as the most common reason for discontinuation. Consistent, objective monitoring of treatment response and timely switch to effective therapy is needed in patients with RA.

60 kD Ro and nRNP A frequently initiate human lupus autoimmunity.

Systemic lupus erythematosus (SLE) is a clinically heterogeneous, humoral autoimmune disorder. The unifying feature among SLE patients is the production of large quantities of autoantibodies. Serum samples from 129 patients collected before the onset of SLE and while in the United States military were evaluated for early pre-clinical serologic events. The first available positive serum sample frequently already contained multiple autoantibody specificities (65%). However, in 34 SLE patients the earliest pre-clinical serum sample positive for any detectable common autoantibody bound only a single autoantigen, most commonly 60 kD Ro (29%), nRNP A (24%), anti-phospholipids (18%) or rheumatoid factor (15%). We identified several recurrent patterns of autoantibody onset using these pre-diagnostic samples. In the serum samples available, anti-nRNP A appeared before or simultaneously with anti-nRNP 70 K in 96% of the patients who had both autoantibodies at diagnosis. Anti-60 kD Ro antibodies appeared before or simultaneously with anti-La (98%) or anti-52 kD Ro (95%). The autoantibody response in SLE patients begins simply, often binding a single specific autoantigen years before disease onset, followed by epitope spreading to additional autoantigenic specificities that are accrued in recurring patterns.

IL-17 producing CD4+ T cells mediate accelerated ischemia/reperfusion-induced injury in autoimmunity-prone mice.

Elements of the innate and adaptive immune response have been implicated in the development of tissue damage after ischemic reperfusion (I/R). Here we demonstrate that T cells infiltrate the intestine of C57BL/6 mice subjected to intestinal I/R during the first hour of reperfusion. The intensity of the T cell infiltration was higher in B6.MRL/lpr mice subjected to intestinal I/R and reflected more severe tissue damage than that observed in control mice. Depletion of T cells limited I/R damage in B6.MRL/lpr mice, whereas repletion of B6.MRL/lpr lymph node-derived T cells into the I/R-resistant Rag-1(-/-) mouse reconstituted tissue injury. The tissue-infiltrating T cells were found to produce IL-17. Finally, IL-23 deficient mice, which are known not to produce IL-17, displayed significantly less intestinal damage when subjected to I/R. Our data assign T cells a major role in intestinal I/R damage by virtue of producing the pro-inflammatory cytokine IL-17.

Clinical criteria for systemic lupus erythematosus precede diagnosis, and associated autoantibodies are present before clinical symptoms.

OBJECTIVE: Specific events that occur during the development of systemic lupus erythematosus (SLE) can be quite variable among individual patients. The aim of this study was to identify patterns that distinguish early clinical events in SLE and to assess whether the presence of associated autoantibodies precedes the fulfillment of clinical criteria. METHODS: Through a retrospective chart review of military medical records, 130 patients who met the American College of Rheumatology (ACR) criteria for the classification of SLE were identified. The initial time at which each criterion was fulfilled was recorded. Autoantibody analysis was performed on serum samples, using enzyme-linked immunosorbent assays or immunofluorescence. RESULTS: The clinical features that were observed earliest were discoid rash and seizures, which developed a mean 1.74 and 1.70 years, respectively, before the diagnosis of SLE; however, arthritis was the criterion that was most commonly observed before diagnosis. The presence of IgG rheumatoid factor (IgG-RF) preceded the development of arthritis in 15 (94%) of the 16 patients who were positive for IgG-RF and in whom arthritis developed (Z = 10.2, P < 0.0001). Analogously, IgM-RF appeared before the development of arthritis in 13 (76%) of 17 patients. Anti-double-stranded DNA antibodies were associated with renal disease and appeared before evidence of nephritis in most patients (92%) (Z = 13.3, P < 0.0001). An analysis of the appearance of autoantibodies compared with the appearance of clinical criteria not associated with them revealed no significant temporal relationship. CONCLUSION: Symptoms associated with the ACR criteria for classification of SLE are commonly present before the diagnosis of SLE, and development of organ-associated autoantibodies generally precedes the appearance of their associated clinical features.

Topotecan-induced bronchiolitis.

Topotecan HCl is an antitumor drug exhibiting topoisomerase 1-inhibitory activity. Topotecan is used in the treatment of metastatic carcinoma of the ovary and as second-line treatment of small-cell lung cancer. Reported dose-limiting adverse reactions to topotecan are primarily hematologic in nature. To date, only one other case of lung toxicity in a patient taking topotecan has been reported. The authors describe the development of obliterative bronchiolitis, as evidenced by radiographic and pulmonary function testing abnormalities, in a 61-year-old woman who presented with dyspnea, and who was receiving topotecan for peritoneal carcinomatosis.