Anakinra Treatment Research Articles

Chronic Pancreatitis in a Patient with Schnitzler Syndrome, A Rare Disorder of Dysfunctional Inflammasome/IL-1 Regulation

Purpose: Schnitzler syndrome, a rare autoimmune inflammatory disorder, is characterized by chronic urticaria, IgM gammopathy, and systemic inflammation, e.g., fever, leukocytosis, lymphadenopathy, and arthritis. We present a case of acute on chronic pancreatitis in a patient with Schnitzler syndrome, a condition not previously clearly associated with chronic pancreatitis. A 50-year-old white female with a complicated past medical history including recurrent abdominal pain, pancreatitis, leukocytosis, urticaria and IgM gammopathy presented with worsening abdominal pain. Pain started 4 days prior to admission and was located over the epigastric and periumbilical areas. Pain was sharp, without aggravating or alleviating factors. Associated symptoms included chronic diarrhea, fatigue, and weight loss. The diagnosis of Schnitzler syndrome was made three years ago at another hospital when the patient presented with, among other symptoms, chronic abdominal pain. Her condition resolved with IL-1R antagonist, Anakinra, injection. Unfortunately, she stopped Anakinra treatments due to financial constraints, resulting in frequent hospital admissions mostly for intractable abdominal pain and diarrhea. Past surgical history included pancreatic cyst drainage at age of 10. Patient denied alcohol use. Family history was positive for alcoholic pancreatitis. Physical examination revealed a stable but cachectic female. Abdomen was soft, mildly distended with normoactive bowel sounds, and tender to palpation. Relevant laboratory results included WBC 39,600, amylase 6, lipase 46, alkaline phosphatase 226, AST 8, ALT 22, and Clostridium difficile-negative stool. Abdominal CT showed a diffusely calcified pancreas consistent with chronic pancreatitis. The patient was managed conservatively for acute on chronic pancreatitis. Upon stabilization, she was arranged for transfer to a nearby university center for management of her underlying Schnitzler syndrome. IL-1, a key pathogenetic cytokine in Schnitzler syndrome, also contributes to the development of chronic pancreatitis. In mice, IL-1β overexpression in the pancreas induces chronic pancreatitis; IL-1R antagonist attenuates disease progression. IL-1β is processed by the inflammasome, an intracellular multiprotein complex. A gain-of-function mutation in NLRP3 inflammasome has been identified in a patient with Schnitzler syndrome. Therefore, therapy that targets the inflammasome/IL-1 pathway can be expected to ameliorate chronic pancreatitis secondary to Schnitzler syndrome. We also propose that Schnitzler syndrome be considered among the differential diagnoses for patients presenting with unexplained chronic pancreatitis.

P153 Interleukin-6 levels as indicator of macrophage activation syndrome/relaps in systemic juvenile arthritis during anakinra or tocilizumab treatment

Introduction Systemic juvenile idiopathic arthritis (sJIA) without arthritis is a subtype of chronic childhood arthritis of presumed autoinflammatory etiology. It is characterized by prolonged period of spiking fever, skin rash, lymphadenopathy, hepatosplenomegaly, and serositis. Macrophage activation syndrome (MAS), a potentially fatal complication is seen most frequently in this juvenile rheumatic disease. MAS is diagnosed based on the combination of clinical symptoms, cytopenia or sudden decrease of white blood cells and/or platelet count, coagulopathy, and liver dysfunction in the absence of infection. Ample evidence supports the hypothesis that MAS is one of many presentations of cytokine storm scenarios in human diseases. Some of these cytokines are target molecules of biologic therapy in sJIA such as interleukin (IL)-1 and IL-6. In addition to anakinra, recombinant IL-1RA, a tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, is approved for treatment of sJIA also. Methods Here we present a comparison of laboratory findings of two separate acute non-infectious exacerbations in a 6 years old girl with multiple-drug resistant sJIA that developed during treatment with anakinra or TCZ. Results Although both treatments resulted in rapid resolution of systemic symptoms initially, anakinra treatment was superior in the length of disease remission. Treatment with anakinra did not interfere with findings of laboratory evaluation recommended for diagnosis of the acute phase of sJIA and/or MAS. In contrast to anakinra, TCZ blocked the production of C-reactive protein while other soluble markers such as serum IL-6, procalcitonin, and ferritin were unaffected. Conclusion These findings indicate that laboratory monitoring of exacerbations in sJIA patients should be tailored based on the type of the blockade of a single cytokine pathway (IL-1 or IL-6).

Efficacy of interleukin-1-targeting drugs in mevalonate kinase deficiency

To describe the efficacy and safety of IL-1-targeting drugs, anakinra and canakinumab, in patients with mevalonate kinase deficiency (MKD). A questionnaire was sent to French paediatric and adult rheumatologists to retrospectively collect information on disease activity before and after treatment with IL-1 antagonists from genetically confirmed MKD patients. We assessed the frequency of crises and their intensity using a 12-item clinical score built for the purpose of the study. Eleven patients were included. Anti-IL-1-targeting drugs were used continuously in all but one patient who received anakinra on demand. Daily anakinra (nine patients) or canakinumab injections every 4-8 weeks (six patients, in four cases following anakinra treatment) were associated with complete remission in four cases and partial remission in seven. The median score during MKD attacks decreased from 7/12 before treatment to 3/12 after anakinra and 1/12 after canakinumab. The number of days with fever during attacks decreased from 5 before treatment to 3 after anakinra and 2 after canakinumab. Marked decrease of C-reactive protein and serum amyloid A protein were recorded. Side effects were mild or moderate; they consisted of local pain and inflammation at injection site, infections and hepatic cytolysis. Continuous IL-1 blockade brings substantial benefit to MKD patients. Controlled trials are necessary to further assess the clinical benefit and treatment modalities in these patients.

Chronic inhibition of endoplasmic reticulum stress and inflammation prevents ischaemia‐induced vascular pathology in type II diabetic mice

Endoplasmic reticulum (ER) stress and inflammation are important mechanisms that underlie many of the serious consequences of type II diabetes. However, the role of ER stress and inflammation in impaired ischaemia-induced neovascularization in type II diabetes is unknown. We studied ischaemia-induced neovascularization in the hind-limb of 4-week-old db - /db- mice and their controls treated with or without the ER stress inhibitor (tauroursodeoxycholic acid, TUDCA, 150 mg/kg per day) and interleukin-1 receptor antagonist (anakinra, 0.5 µg/mouse per day) for 4 weeks. Blood pressure was similar in all groups of mice. Blood glucose, insulin levels, and body weight were reduced in db - /db- mice treated with TUDCA. Increased cholesterol and reduced adiponectin in db - /db- mice were restored by TUDCA and anakinra treatment. ER stress and inflammation in the ischaemic hind-limb in db - /db- mice were attenuated by TUDCA and anakinra treatment. Ischaemia-induced neovascularization and blood flow recovery were significantly reduced in db - /db- mice compared to control. Interestingly, neovascularization and blood flow recovery were restored in db - /db- mice treated with TUDCA or anakinra compared to non-treated db - /db- mice. TUDCA and anakinra enhanced eNOS-cGMP, VEGFR2, and reduced ERK1/2 MAP-kinase signalling, while endothelial progenitor cell number was similar in all groups of mice. Our findings demonstrate that the inhibition of ER stress and inflammation prevents impaired ischaemia-induced neovascularization in type II diabetic mice. Thus, ER stress and inflammation could be potential targets for a novel therapeutic approach to prevent impaired ischaemia-induced vascular pathology in type II diabetes.

Two Cases of Refractory Adult-Onset Still's Disease Responding to Anakinra

Adult-onset Still`s disease (AOSD) is a systemic inflammatory disorder with variable clinical features. The interleukin (IL)-1 receptor antagonist anakinra has been proposed as an alternative effective treatment in refractory AOSD. We report, for the first time in Korea, two cases of refractory AOSD in which anakinra treatment produced a clinical response. The first patient had frequent clinical flare-ups with fever, sore throat, myalgia, and pleuritic chest pain despite treatment with methotrexate and etanercept. In the second patient, treatments with various immunosuppressive agents failed to control the disease activity. Treatment with anakinra 100 mg/day was initiated in both cases. A complete clinical remission and improvement in the laboratory parameters were observed. The steroid dose was tapered without further clinical flare-ups. Anakinra appears to be an effective alternative treatment modality in patients with AOSD refractory to conventional disease-modifying anti-rheumatic drugs and corticosteroid therapy. (Korean J Med 2012;82:520-524)

S100 Levels Guided Treatment Options in a Teenage Boy with Relapsing Pericarditis or Atypical Still and #8217;s Disease

Abstract: Unraveling the etiology of recurrent pericarditis in children is often challenging. Here, we describe the case of a previously healthy, 15-year-old boy who presented with fever, cough and thoracic pain due to Pericarditis with a large pericardial effusion. After insertion of a pericardial drainage over 1600 ml of pericardial fluid were collected over a 48-hour period. Laboratory investigations revealed systemic inflammation and negative autoantibodies, but displayed no evidence of an infectious disease. Autoimmune pericarditis was therefore suspected and a combination of glucocorticosteroid and NSAID therapy was initiated. Steroids were able to be gradually tapered. However, the patient suffered a recurrence of pericarditis after six weeks of low-dose steroids and NSAIDs. As with the first episode, arthritis, rash, lymphadenopathy and hepatosplenomegaly were absent. Retrospective analysis of the serum from the initial episode showed significant elevation of S100 protein levels (S100A8/S100A9). As a result, we assumed an atypical presentation of Still´s disease (systemic onset juvenile idiopathic arthritis or SoJIA) and initiated therapy with anakinra, an interleukin-1-receptor antagonist. This treatment led to rapid improvement, and pericardiocentesis was able to be avoided. Four months after the relapse and subsequent initiation of anakinra therapy, no disease reoccurrence has transpired. Treatment with ibuprofen and steroids could be suspended. The patient developed mild arthritic signs during follow-up supporting the diagnosis of SoJIA. A potential differential diagnosis in this case is idiopathic recurrent acute pericarditis (IRAP), a disease of unknown etiology that shows features consistent with an autoinflammatory pathogenesis where recent reports indicated good clinical response to anakinra treatment as well. This case highlights the predictive value of S100 protein levels for the diagnosis of autoinflammatory disorders such as SoJIA - particularly when there is an atypical or oligosymptomatic presentation. Moreover, it illustrates the therapeutic potential of anakinra for autoimmune-mediated pericarditis.

Anakinra: A safe and effective first-line treatment in systemic onset juvenile idiopathic arthritis (SoJIA)

Systemic onset juvenile idiopathic arthritis (SoJIA) is a rare inflammatory disorder. It can result in disease and treatment-related disability. SoJIA is characterized by remitting fevers, evanescent rash, generalized lymphadenopathy, hepatomegaly/splenomegaly, and/or serositis. Non-responsiveness to standard therapy with corticosteroids and disease modifying antirheumatic drugs is not uncommon. IL-1β has been shown to be a main contributor to the pathogenesis of SoJIA. Anakinra, a recombinant IL-1β receptor antagonist, was shown to be effective in small cohorts of therapy-resistant adult and pediatric Still's patients. In order to assess the efficacy and safety of first-line anakinra treatment in SoJIA, we reviewed the charts of all SoJIA patients in our institution from 2005 to 2010, searching for first-line anakinra-treated patients. We report the clinical and laboratory course of four SoJIA patients. The mean follow-up was 13.5 (range: 2-50) months. Anakinra was started at doses from 1.5 to 4 mg/kg for a median duration of 3 (range: 3-18) months. Two patients responded to anakinra mono-therapy; two cases required corticosteroids. Normalized body temperatures and the absence of evanescent rashes were achieved after a median of 4 (range: 2-10) days. We did not see treatment-related adverse reactions other than local injection site inflammation. This is the first single-center series, reporting anakinra as first-line treatment in SoJIA. We show rapid efficacy of anakinra in early SoJIA with reduced treatment-related side effects. A subset of patients remains corticosteroid dependent. Further studies are warranted to follow larger cohorts and to assess long-term safety.

Anakinra treatment in patients with systemic-onset juvenil idiopathic arthritis: “The Valencia Experience”

Methods We retrospectively reviewed the medical records of patients with SoJIA treated with anakinra (1-3 mg/kg/ day) in our unit between December 2004 and july 2010. Anakinra’s effects were studied on several parameters including fever, rash, erythrocyte sedimentation rate, Creactive protein levels, arthritis joints count, assessment of disease activity (by physician and parent/patient) and pain (by parent/patient). Resulting data were analysed to characterize therapies, clinical course and adverse events.

Role of IL-1b in NLRP12-associated autoinflammatory disorders and resistance to anti-IL-1 therapy

Background A new class of autoinflammatory syndromes called NLRP12-associated disorders (NLRP12AD) has been associated with mutations in NLRP12. Conflicting data on the putative role of NLRP12 in IL-1b signaling have been generated in vitro. Aim This prospective study was undertaken to assess the secretion of IL-1b and three IL-1b-induced cytokines (IL-1Ra, IL-6 and TNF-a) in patients’ PBMC cultured ex vivo and to evaluate the patients’ response to recombinant IL-1 receptor antagonist (IL-1Ra, anakinra), a major drug in the treatment of autoinflammatory disorders. Methods Patients’ disease manifestations and cytokine measurements were recorded before anakinra treatment was started, during 14 months of therapy, and after discontinuation of anakinra treatment. Results Spontaneous secretion of IL-1b by patients’ PBMC was found to be dramatically increased (80 to 175-fold) compared to controls. Consistently, anakinra initially led to a marked clinical improvement and to a rapid near-normalization of IL-1b secretion. However, a progressive clinical relapse occurred secondarily, associated with an increase in TNF-a secretion, persistent elevated levels of IL-1Ra and IL-6 and a reactivation of IL-1b secretion. Anakinra was discontinued after 14 months of therapy. Conclusion Our findings provide in vivo evidence of the crucial role of IL-1b in the pathophysiology of NLRP12AD. This is the first time anakinra has been used to treat this disorder. This study provides new insights into the mechanisms underlying resistance to anti–IL-1 therapy observed in few patients with autoinflammatory syndromes. Our data also point to the potential interest of cytokine ex vivo measurements as predictors of response to treatment.

On-demand anakinra treatment is effective in mevalonate kinase deficiency

BackgroundMevalonate kinase deficiency (MKD) is a hereditary autoinflammatory syndrome marked by recurrent attacks of fever and inflammation. Severe enzyme deficiency results in mevalonic aciduria (MA) and milder deficiency in hyperimmunoglobulin...

“Mutation negative” familial cold autoinflammatory syndrome (FCAS) in an 8-year-old boy: clinical course and functional studies

Cryopyrinopathies are a subgroup of autoinflammatory syndromes. Most cases have mutations in the CIAS1/NLRL3 gene, encoding the cryopyrin/NLRP3 protein. Cryopyrin, together with other proteins, is involved in the assembly of the cryopyrin/NLRP3 inflammasome. Mutations in CIAS1/NLRP3 result in increased IL-1β cleavage from biologically inactive pro-IL-1β. This results in systemic inflammation and three associated disorders of different severity, forming a clinical continuum with overlapping features. The mildest from, familial cold autoinflammatory syndrome (FCAS), is characterized by remitting fevers, urticaria-like rash, polyarthralgia/arthritis, and usually caused by cold exposure. More severe forms are Muckle-Wells syndrome (MWS) and CINCA/NOMID. We report an 8-year-old boy with FCAS, who presented with overlapping features with MWS. He showed good response to seasonal anakinra treatment. Mutation analysis in CIAS1/NLRP3, PYCARD, and CASP1 was performed. Serum cytokine profiles, and cytokine expression from resting monocytes, and in response to mild hypothermia, and LPS stimulation were determined. Mutations in CIAS1/NLRP3, PYCARD, and CASP1 were not found. In response to mild hypothermia, an enhanced IL-1β expression by patient monocytes resulted in increased IL-6 and TNF-α secretion, as compared to control cells. The addition of the IL-1β receptor antagonist (anakinra) reversed these effects. In response to LPS stimulation, patient monocytes produced high level of IL-1β, IL-6 and TNF-α. This was markedly less pronounced in control monocytes. FCAS results in cold-induced cytokine dysregulation and systemic inflammation. Symptoms can be treated, using IL-1β antagonists. Further research is warranted, particularly in order to investigate pathophysiological mechanisms in "mutation negative" individuals.

Role of interleukin-1β in NLRP12-associated autoinflammatory disorders and resistance to anti-interleukin-1 therapy

A new class of autoinflammatory syndromes called NLRP12-associated disorders (NLRP12AD) has been associated with mutations in NLRP12. Conflicting data on the putative role of NLRP12 in interleukin-1β (IL-1β) signaling have been found in in vitro analyses. This prospective study was undertaken to assess the secretion of IL-1β and 3 IL-1β-induced cytokines (IL-1 receptor antagonist [IL-1Ra], IL-6, and tumor necrosis factor α [TNFα]) in patients' peripheral blood mononuclear cells (PBMCs) cultured ex vivo and to evaluate the patients' response to IL-1Ra (anakinra), a major drug used in the treatment of autoinflammatory disorders. Patients' disease manifestations and cytokine measurements were recorded before anakinra treatment was started, during 14 months of therapy, and after discontinuation of anakinra treatment. Spontaneous secretion of IL-1β by patients' PBMCs was found to be dramatically increased (80-175 fold) compared to healthy controls. Consistent with these findings, anakinra initially led to a marked clinical improvement and to a rapid near-normalization of IL-1β secretion. However, a progressive clinical relapse occurred secondarily, associated with an increase in TNFα secretion, persistent elevated levels of IL-1Ra and IL-6, and a reactivation of IL-1β secretion. Anakinra was discontinued after 14 months of therapy. Our findings provide in vivo evidence of the crucial role of IL-1β in the pathophysiology of NLRP12AD. This is the first time anakinra has been used to treat this disorder. This study provides new insights into the mechanisms underlying resistance to anti-IL-1 therapy observed in a few patients with autoinflammatory syndromes. Our data also point to the potential of ex vivo cytokine measurements as predictors of response to treatment.

Preliminary studies related to anti-interleukin-1β therapy in children with newly diagnosed type 1 diabetes

Interleukin-1β (IL-1β) may play a role in the pathogenesis of type 1 diabetes, but there are no data regarding the efficacy of agents antagonizing IL-1β in patients with this disorder. We characterized the effects of IL-1β on gene expression in peripheral blood mononuclear cells (PBMC) and the clinical and gene expression effects of a short course of recombinant IL-1 receptor antagonist protein, anakinra, on children with newly diagnosed diabetes. PBMC from healthy adult volunteers were exposed to IL-1β for 24 h in vitro. Gene expression was analyzed via microarray. Fifteen children within 1 wk of diagnosis of type 1 diabetes received daily anakinra for 28 d and were followed for 6 months. Blood was drawn for microarray analysis before and after anakinra treatment. Insulin secretory capacity was assessed by mixed-meal tolerance testing (MMTT) at 3-4 wk and 7 months after diagnosis. Hemoglobin A1c (HbA1c) and insulin doses were periodically recorded. Data were compared with two historical control groups of children with newly diagnosed diabetes. Although in vitro exposure to IL-1β caused many changes in PBMC gene expression, gene expression did not change significantly after anakinra therapy in diabetes patients. Anakinra-treated patients had similar HbA1c and MMTT responses, but lower insulin requirements 1 and 4 months after diagnosis compared to controls, and lower insulin-dose-adjusted A1c 1 month after diagnosis. Anakinra therapy is well tolerated in children with newly diagnosed type 1 diabetes. Further studies are needed to demonstrate biological effects.

Treatment with Anakinra Improves Disposition Index But Not Insulin Sensitivity in Nondiabetic Subjects with the Metabolic Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study

Obesity induces low-grade inflammation that may promote the development of insulin resistance. IL-1 is one of the key inflammatory factors. The objective of the study was to demonstrate improvement of insulin sensitivity by blocking IL-1. This was a randomized, double-blind, crossover study. The study was based on ambulatory care. Participants included nondiabetic, obese subjects with the metabolic syndrome. Intervention included 150 mg anakinra sc once daily or matching placebo for 4 wk. Insulin sensitivity as measured by euglycemic hyperinsulinemic clamp. A total of 13 of 19 subjects completed the study. Although anakinra treatment resulted in a significantly lower level of inflammation illustrated by a reduction in circulating C-reactive protein concentrations and leukocyte numbers, insulin sensitivity was not significantly different after anakinra treatment (2.8 × 10(-2) ± 0.5 × 10(-2)) compared with placebo treatment (2.4 × 10(-2) ± 0.3 × 10(-2) μmol/kg(-1) · min(-1) · pmol(-1), P = 0.15). Adipose tissue examination, performed to analyze local effects of IL-1 receptor antagonist, showed an increased influx of macrophages after treatment with anakinra most likely due to an injection site reaction caused by the vehicle (0.28 ± 0.05 vs. 0.11 ± 0.01 macrophages per adipocyte, P = 0.005). The differences in individual subject insulin sensitivity after anakinra as compared with placebo between subjects were negatively correlated with macrophage infiltration into the adipose tissue (r(2) = 0.46, P = 0.01). The disposition index increased significantly after anakinra treatment (P = 0.04), reflecting an improvement in β-cell function. Our results suggest that anakinra does not improve insulin sensitivity in obese, insulin-resistant, nondiabetic subjects.

Recurrent AA Amyloidosis in a Kidney Transplant

Recurrent AA amyloidosis in a kidney transplant is rare, especially when the underlying inflammatory condition is controlled. We present a 59-year-old man who underwent a living donor kidney transplant 17 years ago for kidney failure due to AA amyloid nephropathy in the setting of long-standing Crohn disease. His Crohn disease was quiescent before and after the kidney transplant. Transplant function had been stable until a month before presentation, when he developed worsening proteinuria and decreased kidney function. A transplant biopsy showed recurrent AA amyloidosis despite excellent clinical and histologic control of Crohn disease.

Failure of anakinra treatment of pyoderma gangrenosum in an IBD patient and relevance to the PSTPIP1 gene

Failure of anakinra treatment of pyoderma gangrenosum in an IBD patient and relevance to the PSTPIP1 gene

Anakinra effects on T cells in patients with refractory idiopathic inflammatory myopathies

Background and objectivesInterleukin 1 (IL-1) is overexpressed in muscle tissue of inflammatory myopathies. A clinical response to IL-1 blockade with anakinra was seen in 7/15 patients with refractory myositis, but...

Mouse granzyme K has pro-inflammatory potential

Granzymes (gzms) are key components of T-killer (Tc) cells believed to mediate pro-apoptotic activities. Recent evidence suggests that gzms also possess non-cytotoxic activities that contribute to host defense. In this study, we show that Tc cells from lymphocytic choriomeningitis virus (LCMV)-infected wild-type (wt) and gzm A/B-deficient mice express similar levels of gzmK protein, with both mouse strains efficiently controlling infection. GzmK, in recombinant form or secreted by ex vivo-derived LCMV-immune gzmAxB(-/-) Tc cells, lacks pro-apoptotic activity. Instead, gzmK induces primary mouse macrophages to process and secrete interleukin-1β, independent of the ATP receptor P2X(7). Together with the finding that IL-1Ra (Anakinra) treatment inhibits virus elimination but not generation of cytotoxic Tc cells in wt mice, the data suggest that Tc cells control LCMV through non-cytotoxic processes that involve gzmK.

Failure of anakinra treatment of pyoderma gangrenosum in an IBD patient with microsatellite variation in the promoter region of the PSTPIP1 gene.

Failure of anakinra treatment of pyoderma gangrenosum in an IBD patient with microsatellite variation in the promoter region of the PSTPIP1 gene.

Intra-articular Anakinra for the Treatment of Persistent Inflammation and Arthrofibrosis following Anterior Cruciate Ligament Reconstruction

ABSTRACT Purpose Postoperative inflammation and arthrofibrosis remain difficult problems following ACL reconstruction. Interleukin-1 (IL-1) is a potent driver of intra-articular inflammation and arthrofibrosis following injury and surgery. Anakinra (Kineret, Amgen, Thousand Oaks, CA) is an IL-1 receptor antagonist. We hypothesize that postoperative intra-articular anakinra use decreases inflammation and subsequent arthrofibrosis, reducing the need for arthroscopic debridement and manipulation under anesthesia. Methods Four patients (ages 15-56) who were treated with anakinra for persistent postoperative inflammation and scarring within 4 months of ACL reconstruction were retrospectively reviewed. Anakinra was utilized when patients were unable to obtain full extension and at least 90° of flexion 1 month postoperatively in association with persistent effusions or decreased patellar mobility. Results Anakinra injection was performed between 36 and 97 days postsurgery. All four reported improvements in range of motion and decreased pain and effusions within 10 days of injection. One patient, who did not receive anakinra until more than 3 months postsurgery, required eventual arthroscopic debridement of a cyclops lesion but none of the patients required frank lysis of adhesions or manipulation under anesthesia. No adverse reactions to anakinra occurred. Conclusion Based on previous experience, we believe that all of these patients would have required arthroscopic debridement of scar tissue and manipulation under anesthesia to regain motion were not for the anakinra treatment. Clearly, the concept of IL-1 inhibition in the postoperative knee requires further research, but early results are promising for this unique treatment of a difficult clinical problem.