anakinra (PerkinRA)

A 24-Year-Old Man with Disseminated Tuberculosis and A Corticosteroid-Refractory Paradoxical Reaction to Anti-Tuberculous Treatment.

Charalampidis Charalampos C, Karantana Valentina V, Kavatha Dimitra D, Tsiodras Sotirios S et al.

Paradoxical reactions during anti-tuberculosis treatment are immune-mediated reactions that complicate treatment even in immunocompetent patients. We present the case of a previously healthy 24-year-old man with disseminated tuberculosis, who experienced persistent fever, weight loss, and radiological deterioration despite appropriate treatment. These findings were consistent with a paradoxical reaction to treatment, after extensive work-up excluded treatment failure, co-infections, and systemic inflammatory conditions. However, high-dose corticosteroids failed to achieve improvement. Ultimately, an interleukin-1 receptor antagonist (anakinra) was initiated as a salvage therapy for this corticosteroid-refractory paradoxical reaction, resulting in rapid defervescence, normalization of inflammatory markers, and radiological improvement. This case underscores the diagnostic and therapeutic challenges when managing severe reactions in tuberculosis patients, while highlighting the importance of biologics like anakinra in corticosteroid-refractory paradoxical reactions. Paradoxical reactions to anti-tuberculosis treatment remain an overlooked cause of non-resolving fever in immunocompetent and immunocompromised patients with tuberculosis and should be considered after ruling out treatment-refractory or complicated infection in persistently febrile patients.Prompt treatment of severe reactions prevents major complications and improves clinical outcomes.Corticosteroid-refractory paradoxical reactions illustrate the potential role of biologics, such as tumour necrosis factor inhibitors and, in our case, interleukin-1 receptor antagonists, in controlling excessive inflammation in tuberculosis.

Malignancy-Associated Hemophagocytic Lymphohistiocytosis: Clinical Characteristics, Treatment Patterns, and Survival Outcomes in a Tertiary Care Center Cohort.

Kosch Ricardo R, Alsdorf Winfried W, Ahmadi Paymon P, Hölzemer Angelique A et al.

Malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH) carries a poor prognosis and is often complicated by overlapping infection, cytopenias, organ failure, and progressive disease. We retrospectively analyzed 49 adults with M-HLH at a single tertiary cancer center (2013-2026), summarizing malignancy spectrum, diagnostic features, treatment, and survival outcomes. HLH probability was assessed by HScore and modified HLH-2004 criteria. Lymphoma was the main underlying disease (34/49; 69.4%), led by aggressive B-cell (17/49; 34.7%) and T-cell NHL (12/49; 24.5%). HLH coincided with initial malignancy recognition in 17 of 49 patients (34.7%). The median HScore was 231 (IQR 202-256); 44 of 49 patients (89.8%) met the ≥ 169 threshold, and 42 of 49 patients (85.7%) fulfilled ≥ 5 of 7 modified HLH-2004 criteria. HLH-directed therapy included corticosteroids (41/49; 83.7%), etoposide (21/49; 42.9%), and anakinra (16/49; 32.7%); 21 of 49 patients (42.9%) received concurrent malignancy-directed chemotherapy. Mortality was 59.2% (29/49) with a median overall survival of 56 days (median follow-up 612 days for the cohort; 574 days among survivors, n = 20). De novo presentation carried substantially lower mortality than HLH in previously known malignancy (23.5% vs. 78.1%; hazard ratio [HR] 5.38, 95% confidence interval [CI], 1.85-15.61; P = .002). Malignancy-directed chemotherapy was associated with lower mortality than HLH-directed therapy alone (HR 3.11, 95% CI, 1.36-7.09; P = .007). All 6 patients with invasive mold infection died. M-HLH was predominantly lymphoma-associated, met diagnostic criteria with high probability, and carried poor short-term survival. De novo presentation had better outcomes, likely because lymphoma-directed chemotherapy can simultaneously address the underlying malignant trigger and the hyperinflammatory state. Invasive mold infection was uniformly fatal, illustrating the lethal combination of profound immunosuppression and uncontrolled opportunistic infection in this setting.

INTERLEUKIN-1 RECEPTOR ANTAGONIST LEVELS IN PATIENTS WITH HEART FAILURE AND REDUCED EJECTION FRACTION TREATED WITH ANAKINRA.

Kelly Jazmin J, Mezzaroma Eleonora E, Roscioni Andrea A, McSkimming Chantel C et al.

Patients with heart failure and reduced ejection fraction (HFrEF) commonly show signs of systemic inflammation. Interleukin-1 (IL-1) is a pro-inflammatory cytokine, known to modulate cardiac function. We aimed to determine the effects of treatment with anakinra, a recombinant IL-1 receptor antagonist (IL-1Ra), on plasma IL-1Ra levels. We measured IL-1Ra levels at baseline and longest available follow-up to 24 weeks in 63 patients (44 males, 40 self-identified Black-Americans) with recent hospitalization for HFrEF, and systemic inflammation (C-reactive protein [CRP] levels >2 mg/L) who were assigned to anakinra (n=42 [66.7%]) or placebo (n=21 [33.3%]) as part of the REDHART2 clinical trial (NCT03797001). Cardiorespiratory fitness was measured as peak oxygen consumption (VO2peak). Baseline plasma IL-1Ra levels were 380 [290 to 1046] pg/mL. On-treatment IL-1Ra levels were significantly higher in the patients treated with anakinra vs. placebo (3,994 [3,372 to 5,000] pg/mL vs. 492 [304 to 1370] pg/mL, P<0.001). The longest available follow-up was 6 weeks in 10 patients (15.9%), 12 weeks in 12 patients (19%), and 24 weeks in 41 patients (65.1%). On-treatment IL-1Ra levels and interval change in IL-1Ra showed a modest inverse correlation with on-treatment CRP levels (R=-0.269, P=0.033 and R=-0.355, P=0.004, respectively) and no statistically significant correlations with VO2peak values (P>0.05). Patients with recently decompensated HFrEF and systemic inflammation treated with recombinant IL-1Ra, anakinra, have a significant several-fold increase in plasma IL-1Ra levels. On-treatment IL-1Ra levels however show only a modest correlation with CRP levels and not with VO2peak.

Letter by Ali et al Regarding Article "Resolution of Systemic Inflammation in Patients With Recently Decompensated Heart Failure With Reduced Ejection Fraction With and Without Interleukin-1 Blockade by Anakinra".

Ali Zeeshan Z, Anwar Muhammad M, Subhani Wasiq W