Tocilizumab Discontinuation Research Articles

Treatment of giant cell arteritis with ultra-short glucocorticoids and tocilizumab: results from the extension of the TOPAZIO study.

To assess the maintenance of efficacy of one year of tocilizumab (TCZ) monotherapy after its discontinuation in large vessel-GCA (LV-GCA). 17 patients with active LV-GCA were previously treated with 3 boluses of intravenous methylprednisone and weekly subcutaneous TCZ in monotherapy for 52 weeks. Patients in relapse-free clinical remission at week 52 discontinued TCZ and entered part two, which was a 26-week observational follow-up period. PET/CT was performed in all patients at the end of the 26-week observational period (week 78). End points were the variation in PET vascular activity score (PETVAS) at week 78 compared with baseline and with week 52, and the proportion of patients with relapse-free clinical remission at week 78 and at the end of the follow-up. Compared with baseline, a significant reduction in PETVAS was observed at week 78, mean (95% CI) change -6.6 (-9.5 to -3.7). However, compared with week 52, PETVAS significantly increase 6 months after TCZ discontinuation (week 78), mean (95% CI) change 4.6 (0.7-8.5). The proportion of patients with relapse-free clinical remission at weeks 78 and at the end of the follow-up (median time from TCZ discontinuation 148 weeks) was 11/17 (65%, 95% CI 38-86) and 8/17 (47%, 95% CI 23-72), respectively. Age and sex-adjusted HR (95% CI) for each unit increase of PETVAS indicating subsequent relapse was 1.36 (0.92-2.00). One year of TCZ monotherapy was effective in maintaining drug-free clinical remission in LV-GCA. Changes in PETVAS early after TCZ discontinuation may predict subsequent relapses. ClinicalTrials.gov, NCT05394909.

Taper versus discontinuation of tocilizumab in patients with giant cell arteritis: Real-world experience from a tertiary center

IntroductionFollowing the approval of tocilizumab (TCZ) for giant cell arteritis (GCA), recent studies have shown a high relapse frequency after abrupt discontinuation of TCZ. However, a thorough exploration of TCZ tapering compared to abrupt discontinuation has never been undertaken. Likewise, adverse events have only been scarcely investigated in routine care. This study aimed to compare the incidence of relapses in GCA patients undergoing TCZ tapering compared to abrupt discontinuation. MethodsWe performed a single-center retrospective cohort study from 2012 to 2022. Data from GCA patients treated with TCZ was obtained from the Electronic Patients Record. Relapse-free survival is reported in Kaplan-Meier plots and tapering versus abrupt discontinuation were compared using a Wilcoxon-Brewlos-Gehan test. ResultsWe included 155 patients receiving TCZ treatment for GCA, of which 104 discontinued TCZ. Among the 104 patients discontinuing TCZ, 42 (40 %) experienced a relapse within the first year. A total of 57 patients underwent taper with 6/38 (16 %) and 2/19 (11 %) relapsing while receiving TCZ every second or third week, respectively. In comparison, 59 patients underwent abrupt discontinuation with 27 (46 %) relapsing during follow-up. The patients undergoing abrupt TCZ discontinuation demonstrated a significantly shorter time to relapse compared to all tapered patients (p = 0.02) as well as patients tapered from weekly TCZ treatment to every second week (p < 0.01). Furthermore, 15 % of patients discontinued TCZ due to adverse events. ConclusionThis is the first study indicating that TCZ taper induced longer relapse-free survival than abrupt discontinuation, implying that taper may be favored over discontinuation in patients with GCA.

Tocilizumab discontinuation after remission achievement in patients with adult-onset Still's disease.

Tocilizumab, an IL-6 inhibitor, has been proven effective in patients with adult-onset Still's disease (AOSD). This study aimed to clarify whether tocilizumab can be discontinued after achieving remission and to identify factors relevant to its successful discontinuation. Consecutive patients with AOSD diagnosed according to Yamaguchi's criteria from April 2012 to July 2022, who were treated with tocilizumab, were retrospectively reviewed. Forty-eight patients with AOSD treated with intravenous tocilizumab, with sufficient information, were included. Thirty-eight patients (79.2%) achieved remission after 6 months of tocilizumab treatment, 12 of whom discontinued tocilizumab during remission. Within 1 year after tocilizumab discontinuation, six patients (50.0%) recurred at a mean of 5.5 months, while the other six (50.0%) remained in remission. Between the non-recurrence and recurrence groups, no difference was found in disease activity at tocilizumab discontinuation (systemic feature score, p = 0.24; ferritin, p = 0.46). While the duration of tocilizumab use was not different (p = 0.32), the interval of tocilizumab administration at tocilizumab discontinuation in the recurrence group was 21 (14-35) days, which tended to be shorter than 35 (28-53) days in the non-recurrence group (p = 0.08). Patients with prednisolone dose < 7 mg/day at last tocilizumab treatment had fewer recurrences than those without (p = 0.001). After recurrence, tocilizumab was resumed in half of the patients, resulting in successful disease control. The recurrence rate after tocilizumab discontinuation was 50% in 1 year. Patients who remained in remission with a longer interval of tocilizumab administration and lower prednisolone dose were likely to succeed in the withdrawal of tocilizumab.

The Meteoritics Trial: efficacy of methotrexate after remission-induction with tocilizumab and glucocorticoids in giant cell arteritis—study protocol for a randomized, double-blind, placebo-controlled, parallel-group phase II study

BackgroundGlucocorticoids (GC) are the standard treatment for giant cell arteritis (GCA), even though they are associated with adverse side effects and high relapse rates. Tocilizumab (TCZ), an interleukin-6 receptor antagonist, has shown promise in sustaining remission and reducing the cumulative GC dosage, but it increases the risk of infections and is expensive. After discontinuation of TCZ, only about half of patients remain in remission. Additionally, only few studies have been conducted looking at remission maintenance, highlighting the need for alternative strategies to maintain remission in GCA. Methotrexate (MTX) has been shown to significantly decrease the risk of relapse in new-onset GCA and is already a proven safe drug in many rheumatologic diseases.MethodsThis study aims to evaluate the efficacy and safety of MTX in maintaining remission in patients with GCA who have previously been treated with GC and at least 6 months with TCZ. We hypothesize that MTX can maintain remission in GCA patients, who have achieved stable remission after treatment with GC and TCZ, and prevent the occurrence of relapses. The study design is a monocentric, randomized, double-blind, placebo-controlled, parallel-group phase II trial randomizing 40 GCA patients 1:1 into a MTX or placebo arm. Patients will receive 17.5 mg MTX/matching placebo weekly by subcutaneous injection for 12 months, with the possibility of dose reduction if clinically needed. A 6-month follow-up will take place. The primary endpoint is the time to first relapse in the MTX group versus placebo during the 12-month treatment period. Secondary outcomes include patient- and investigator-reported outcomes and laboratory findings, as well as the prevalence of aortitis, number of vasculitic vessels, and change in intima-media thickness during the study.DiscussionThis is the first clinical trial evaluating remission maintenance of GCA with MTX after a previous treatment cycle with TCZ. Following the discontinuation of TCZ in GCA, MTX could be a safe and inexpensive drug.Trial registrationClinicalTrials.gov, NCT05623592. Registered on 21 November 2022.EU Clinical Trials Register, 2022-501058-12-00.German Clinical Trials Register DRKS00030571.

Acute myeloid leukemia developed through myeloproliferative features during immunosuppressive therapy for juvenile idiopathic arthritis.

A 17-year-old male with thrombocytosis and exacerbation of arthralgia during intensified immunosuppressive therapy with tocilizumab, prednisolone, and methotrexate for juvenile idiopathic arthritis (JIA) was referred to our department. Bone marrow examination revealed myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U). Peripheral myeloblasts disappeared temporarily after discontinuation of tocilizumab but progressed to acute myeloid leukemia six months after the development of MDS/MPN-U. The patient sustained complete remission after unrelated bone marrow stem cell transplantation, followed by chemotherapy. The arthralgia also improved after chemotherapy. The possibility of developing malignancies during immunosuppressive therapy in patients with JIA should be considered. J. Med. Invest. 71 : 335-339, August, 2024.

Successful use of extracorporeal membrane oxygenation for life‐threatening macrophage activation syndrome after treatment with tocilizumab in an systemic juvenile idiopathic arthritis patient

AbstractMacrophage activation syndrome (MAS) is a rare, potentially life‐threatening condition in rheumatic diseases. The primary treatments consist of high‐dose corticosteroids and immunosuppressive drugs, although more recently, cytokine inhibitors like anakinra or tocilizumab (TCZ) have been reported. We present a case of a child with systemic juvenile idiopathic arthritis (sJIA). After receiving a single infusion of TCZ, the child developed progressive hypoxia and was subsequently transferred to the pediatric intensive care unit (PICU) after 4 days. An immediate postintubation chest X‐ray revealed a diffuse exudative lesion. Despite continuous efforts to provide mechanical ventilation and respiratory support, the patient's oxygen saturation continued to decline. Moreover, the patient developed hemodynamic compromise, necessitating the administration of norepinephrine. Eventually, vasopressin and dopamine were added to maintain stable hemodynamics. After an intensive but ineffective treatment, extracorporeal membrane oxygenation (ECMO) was initiated in the PICU after 16 h. The patient successfully recovered and was weaned off ECMO support after 60 h. Following discharge from the PICU, given the severe refractory clinical features, we made an attempt to readminister TCZ treatment. However, within half an hour of TCZ infusion, the patient experienced anaphylaxis characterized by palpitations and chest tightness, leading to the discontinuation of TCZ. TCZ, as a biological agent, is commonly used in the treatment of sJIA. Nonetheless, the occurrence of MAS and anaphylaxis following TCZ administration for sJIA may be more prevalent than previously recognized. Pediatric rheumatologists should exercise caution when initiating TCZ for active sJIA. Furthermore, we want to underscore the importance of life‐saving techniques such as ECMO for sJIA patients in emergency situations.

Efficacy and management of tocilizumab in polymyalgia rheumatica: results of a multicentre retrospective observational study.

The efficacy of anti-IL-6 receptors such as tocilizumab (TCZ) was demonstrated in patients with PMR in two recent randomized controlled trials. The objective of this multicentre retrospective study was to assess the efficacy of TCZ in PMR patients requiring glucocorticoid (GC)-sparing treatment, as well as different strategies for TCZ withdrawal. We conducted a multicentre study in French tertiary healthcare departments for patients with PMR. PMR patients receiving off-label TCZ between 2015 and 2022 were included. The primary endpoint was the proportion of patients tapering to GCs ≤5 mg/day 6 months after the first TCZ infusion. The secondary endpoints were the proportion in whom GC was discontinued during follow-up, and the proportion of patients in whom TCZ was discontinued. Fifty-three PMR patients were included. Thirty-one patients suffered from active PMR despite conventional synthetic DMARDs. GCs were ≤5 mg/day in 77% of the patients (95% CI 36-89) at 6 months, and in 97% of the patients at 12 months. Six and 12 months after the first TCZ infusion, the proportions of GC-free patients were 22.5% (95% CI 12.7-37.8) and 58.3% (95% CI 43.2-74.1), respectively. Among TCZ withdrawal strategies, TCZ infusion spacing and TCZ dose reduction were more successful (success in 87% and 79% of attempts, respectively) than TCZ discontinuation (success in 52% of attempts; P = 0.012 and P = 0.039, respectively). In GC-dependent PMR patients, treatment with TCZ led to a drastic decrease in GC dose and remission of PMR. TCZ dose reduction or TCZ infusion spacing are good options to consider in TCZ withdrawal.

Tocilizumab-induced mucosal injury in the terminal ileum mimicking intestinal Behçet's disease: A case report.

Tocilizumab, a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody, is used for the treatment of adult-onset Still disease (AOSD). Despite its efficacy in many clinical situations, concerns have been raised regarding intestinal mucosal injury in patients receiving tocilizumab. A 64-year-old woman with a history of AOSD was admitted to our hospital with hematochezia. She had AOSD for 15 years and underwent treatment with biweekly tocilizumab 9 months prior to admission. Colonoscopy revealed a large punched-out ulcer in the terminal ileum. On pathological evaluation, nonspecific enteritis with lymphocytes and eosinophils were seen. Based on the location and shape of the lesion, we suspected intestinal Behçet's disease. However, the ulcer reduced in size over time by discontinuation of tocilizumab without additional drug treatment, indicating that it was a drug-induced ulcer. The patient was diagnosed with tocilizumab-induced small intestinal ulcer. The patient treated with the discontinuation of tocilizumab. The discontinuation of tocilizumab resulted in ulcer scarring. There was no recurrence of hematochezia. Tocilizumab can cause deep ulcerative lesions in the terminal ileum, which may resemble intestinal Behçet's disease. It is important to continuously monitor abdominal symptoms during tocilizumab therapy and aggressively perform colonoscopy when hematochezia or abdominal pain is observed.

Relapse Risk and Safety of Long-Term Tocilizumab Use Among Patients With Giant Cell Arteritis: A Single-Enterprise Cohort Study.

To evaluate the safety and efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) in a large North American cohort. Patients with GCA treated with TCZ between January 1, 2010, and May 15, 2020, were retrospectively identified. Kaplan-Meier methods were used to estimate time to TCZ discontinuation and time to first relapse after TCZ discontinuation. Poisson regression models were used to compare annualized relapse rates before, during, and after TCZ use. Age- and sex-adjusted risk factors associated with relapse on and off TCZ and development of adverse events of significant interest (AESIs) were examined using Cox models. One hundred fourteen patients (60.5% female) were included with mean (SD) age 70.4 (8.2) years. Median duration from GCA diagnosis to TCZ start was 4.5 months. Median overall duration of TCZ treatment was 2.3 years. Relapse rate prior to TCZ start (0.84 relapses/person-year) was 3-fold reduced while on TCZ (0.28 relapses/person-year; P < 0.001) but increased to 0.64 relapses/person-year after TCZ discontinuation. Fifty-two patients stopped TCZ after a median of 16.8 months; 27 relapsed after discontinuation (median: 8.4 months; 58% relapsed within 12 months). Only 14.9% of patients stopped TCZ because of AESIs. Neither dose/route of TCZ, presence of large-vessel vasculitis, nor duration of TCZ therapy prior to discontinuation predicted relapse after TCZ stop. TCZ is well tolerated in GCA, with low rates of discontinuation for AESIs. However, relapse occurred in > 50% despite median treatment > 12 months. Since the duration of TCZ prior to discontinuation did not significantly affect subsequent risk of GCA recurrence, further research is needed to determine the optimal duration of therapy.

Outcomes during and after long-term tocilizumab treatment in patients with giant cell arteritis

ObjectiveTo assess outcomes in giant cell arteritis (GCA) patients during and after long-term tocilizumab (TCZ) treatment.MethodsRetrospective analysis of GCA patients treated with TCZ at a single centre (2010–2022). Time to...

Efficacy and safety of canakinumab as a second line biologic after tocilizumab treatment failure in children with systemic juvenile idiopathic arthritis: A single-centre cohort study using routinely collected health data.

A significant number of systemic juvenile idiopathic arthritis (sJIA) patients discontinue biologic disease-modifying antirheumatic drugs (bDMARDs) due to lack of efficacy or safety concerns. Studies of biologic therapy switch regimens in sJIA are required. Patients with sJIA who switched from tocilizumab (due to lack of efficacy or safety) to canakinumab (4 mg/kg every 4 weeks) and were hospitalized at the rheumatology department from August 2012 to July 2020 were included. Primary efficacy outcomes were 30% or greater improvement based on the paediatric criteria of the American College of Rheumatology (ACR30), achievement of inactive disease (JADAS-71 = 0) and clinical remission (ACR sJIA clinical inactive disease criteria). Follow-up from time first canakinumab dose administered was 12 months or the closest time point (not less than 6 and not more than 18 months). Data were extracted from electronic outpatient medical records. During the study period, 46 patients with sJIA switched from tocilizumab to canakinumab. Median age at baseline was 8.2 [interquartile range (IQR) 4.0-12.9] years, with the median sJIA duration being 1.8 (IQR 0.8-5.8) years; 37 (80%) patients received at least one conventional DMARD (cDMARD; oral corticosteroids, methotrexate and/or cyclosporine A). Study outcomes were followed up in 45 patients (one patient did not attend the follow-up for an unknown reason); median follow-up was 359 (IQR 282-404) days. During the follow-up, 1 patient discontinued canakinumab due to tuberculosis detection and the dose was reduced or the injection interval increased in 4 (9%) patients. In total, 27 (60%) patients continued to receive at least one cDMARD. Improvement according to the ACR30 criteria was achieved in 43 patients [96%; 95% confidence interval (CI) 85-99], inactive disease in 42 (93%; 95%CI 82-98), and remission in 37 (82%; 95% CI 69-91); after adjustment for actual time-at-risk, the rates were 83, 85 and 73 events per 100 person-years, respectively. During follow-up, 23 AEs (most frequently infections) were reported in 19/45 (42%) patients; 5/45 (11%) patients developed macrophage activation syndrome, with a favorable outcome in all cases. One-year canakinumab therapy was found to be potentially effective as second-line biologic therapy after discontinuation of tocilizumab in patients with sJIA.

Effectiveness of a two-year tapered course of tocilizumab in patients with giant cell arteritis: A single-centre prospective study

ObjectiveTo evaluate the feasibility of tocilizumab tapering and withdrawal in patients with giant cell arteritis (GCA). MethodsGCA patients eligible for tocilizumab were prospectively enrolled. Tocilizumab was administered weekly for the first 12 months, every-other-week for an additional 12 months, then discontinued. Relapses on tocilizumab were managed with temporary increases in systemic glucocorticoids or addition of methotrexate. Primary outcome was relapse-free survival at month 6 after tocilizumab suspension. Relapse-free survival on tocilizumab, imaging response, and adverse events were evaluated. Results23 GCA patients were enrolled. Reasons for tocilizumab start were relapse (n = 14), persistence of activity (n = 5), or steroid-related adverse events (n = 4). At tocilizumab start, two patients were on methotrexate, which was maintained. Fourteen patients had extracranial vascular involvement on 18FDG-PET/CT. During the first 12 months, four patients (17%) had clinical relapse. At every-other-week tocilizumab start, all patients were in clinical remission, two patients had active vasculitis on 18FDG-PET/CT; two patients were on steroid therapy, and four patients were taking methotrexate. Two patients (9%) relapsed while on every-other-week tocilizumab. At tocilizumab suspension, no patient was on steroid therapy and no patient had signs of active vasculitis on 18FDG-PET/CT. In the 6 months after tocilizumab discontinuation, six patients (26%) relapsed. No new or unexpected safety findings were identified. ConclusionTocilizumab tapered over a two-year period was effective to induce and maintain remission in GCA. Relapses on tocilizumab were minor and responded to incremental changes in therapy. A significant proportion of patients relapsed in the 6 months after therapy suspension.

Comparing the effectiveness and safety of Abatacept and Tocilizumab in elderly patients with rheumatoid arthritis.

The number of biological DMARDs (bDMARDs) used in elderly patients with rheumatoid arthritis (RA) has increased in recent years. We aimed to compare the drug retention rates and safety of abatacept (ABT) and tocilizumab (TCZ) in elderly patients with RA. A total 125 elderly patients with RA (>65 years) who began therapy with either ABT (n = 47) or TCZ (n = 78) between 2014 and 2021 at our institute were enrolled. We compared the drug retention rate and clinical response at 24 weeks between elderly patients with RA treated with ABT and those treated with TCZ. Adverse events (AEs) and the reasons for drug discontinuation were assessed. There was no significant difference in demographic characteristics except for the use of glucocorticoid between the ABT and TCZ groups. There was no significant difference in the drug retention rate between the ABT and TCZ groups. Furthermore, there was no significant difference in the discontinuation rates due to the lack of effectiveness between these two groups. The proportions of the patients archiving low disease activity at 24 weeks did not differ significantly between the two groups. Whereas, the discontinuation rates due to AEs, including interstitial lung disease (ILD), seemed higher in the TCZ group than in the ABT group. In TCZ-treated group, the concomitant use of methotrexate (MTX) significantly increased the incidences of AEs leading to the discontinuation of TCZ. Whereas these was no significant impact of concomitant use of MTX on the incidences of AEs leading to discontinuation in ABT-treated group. In elderly patients with RA treated with ABT and TCZ, drug retention rates were equivalent between the two groups. There were some differences in safety profiles between ABT and TCZ, and the rates of discontinuation due to AEs, including ILD, seem to be lower with ABT than with TCZ in elderly patients with RA.

АНАЛИЗ ВЫЖИВАЕМОСТИ ГЕННО-ИНЖЕНЕРНОЙ БИОЛОГИЧЕСКОЙ ТЕРАПИИ ПРИ ЮВЕНИЛЬНОМ ИДИОПАТИЧЕСКОМ АРТРИТЕ

The problem of the survival of various genetically engineered biological drugs (GEBD) is of a current scientific interest. A clear analysis of the reasons for the withdrawal coupled with the GEBD switching algorithmizing would allow developing of the individual treatment plans and monitoring of the patients. The objective of the study was to analyze the survival of genetically engineered biological therapy in children with juvenile idiopathic arthritis (JIA) through identifying the frequency and structure of cases of switching/cancellation of GEBD. Materials and methods: based on the data obtained from the Moscow registry of children with rheumatic diseases, an observational analytical cross-sectional study was conducted, including patients with JIA aged 0 to 17 years old living in Moscow, who had a history of episodes of switching or cancellation of GEBD. The study was conducted from January, 2015 to December, 2021. Results: 1220 patients (35.8% male/64.2% female) with JIA were included in the study. The median age of patients was 11.0 (8.0; 15.0) years. The total number of prescribing of GEBD of the first and subsequent lines was 589 episodes in 531 patients, of which 46 patients had 64 episodes of switching or cancellation of GEBD, which accounted for 10.9% of all cases of prescribing of GEBD. In the structure of the reasons for the therapy change the secondary failure accounted for 57.8%, the primary failure - 12.5%, intolerance - 10.9%, de novo uveitis - 9.4%. Cancellation of the drug therapy due to the achievement of remission was noted in 6.2% of cases. There are statistically significant differences in the duration of therapy depending on the reason for discontinuation or replacement of therapy (p&lt;0.001). More often, patients were transferred to adalimumab (29.3%), and when adalimumab was canceled, to tocilizumab and golimumab. In the event of tocilizumab discontinuation, the majority of patients were switched to canakinumab drug therapy. Conclusion: the presented analysis is one of a few studies of such kind that were ever conducted in Russia; it requires further accumulation and analysis of data, including cases of discontinuation of the drug therapy, switching between the drugs, as well as the duration of therapy before the event that caused the change or discontinuation of the drug therapy happened.

Clinical worsening following discontinuation of tocilizumab in diffuse cutaneous systemic sclerosis: a single-centre experience in Japan.

To investigate outcomes following the tapering or discontinuation of tocilizumab in patients with diffuse cutaneous SSc (dcSSc) in a real-world setting. Fifteen patients who were treated with tocilizumab for dcSSc were selected from a single-centre cohort database and were evaluated for serial changes in the modified Rodnan total skin thickness score (mRSS) and predicted forced vital capacity (FVC) and the occurrence of clinical worsening events after the introduction of tocilizumab. Over 12 months of treatment with tocilizumab, the mRSS decreased from 20.4 ± 10.7 to 12.3 ± 8.5 (P = 0.003) and FVC increased from 84.3 ± 13.7% to 88.5 ± 16.4% (P = 0.04). Tocilizumab was tapered or discontinued in seven and three patients, respectively, after improvement in skin thickening without occurrence or progression of organ manifestations. One (14%) of seven patients who underwent tocilizumab tapering experienced a worsening of skin thickening, while all three patients who discontinued tocilizumab experienced a worsening of skin thickening and/or new development of pericarditis, arthritis, interstitial lung disease or pulmonary arterial hypertension. The additional patient who discontinued tocilizumab due to an adverse event experienced subsequent progression of multiple organ manifestations, including skin, lung, lower gastrointestinal and renal involvement, leading to mortality. Our findings suggest potential benefits of prolonged tocilizumab use in dcSSc patients. The discontinuation of tocilizumab can lead to the progression of skin and visceral manifestations. Tapering rather than the discontinuation of tocilizumab is a viable option in dcSSc patients who experience remarkable clinical improvement.

A case of TAFRO syndrome maintained in remission for 5 years after discontinuation of tocilizumab.

TAFRO syndrome is a subtype of idiopathic multicentric Castleman's disease (iMCD) that is characterised by thrombocytopenia, generalised oedema, fever, bone marrow fibrosis, renal failure, and organ enlargement and has a poor prognosis. The prognosis of TAFRO syndrome is worse than that of iMCD-not otherwise specified, with a high mortality rate. There are only a few long-term follow-up reports after remission of TAFRO syndrome with tocilizumab (TCZ) treatment in a patient in whom all drugs were discontinued after attaining sustained remission. Here, we report a case in which interleukin-6 negativity was confirmed and remission was maintained without relapse for 5 years after all drug treatments, including TCZ, were discontinued.

Efficacy and safety of tocilizumab in Behçet's syndrome with refractory arterial lesions: a single-centre observational cohort study in China.

ObjectiveThe aim of this observational cohort study was to assess the effectiveness and safety of the IL-6-receptor inhibitor tocilizumab (TCZ) in Behçet’s syndrome (BS) with refractory arterial involvement.MethodsTen patients admitted to the Rheumatology and Immunology Department of Peking University People’s Hospital between January 2014 and December 2019 were enrolled. The enrolled patients met the BS international criteria and exhibited severe arterial impairments. Refractory arterio-BS was diagnosed based on objective vascular symptoms unexplainable by other known illnesses, and resistance to traditional immunosuppressants and glucocorticoids after 12 weeks. Patients received 8 mg/kg TCZ infusions every 4 weeks for ≥24 weeks, with simultaneous continuation of immunosuppressants and glucocorticoids. Clinical and imaging data were assessed before and after TCZ treatment.ResultsThe enrolled patients were men aged 44.3 (10.5) years; the median disease duration was 186.5 (45.7) months, and the average age of arterial impairment onset was 38.7 (12.9) years. The following trends were observed: improvement and maintenance of symptoms after the 26.8 (7.2)-month follow-up, n = 9; complete remission, n = 6; partial response, n = 3; immunosuppressant dose reduction, n = 4; radiologic improvement of arterial lesions, n = 4; and TCZ discontinuation owing to enlarged abdominal aortic aneurysm relapse, n = 1. The average daily glucocorticoid dose reduced from 54.5 (20.6) to 8.3 (3.6) mg/d (P < 0.001), while the median ESR and CRP values reduced from 50 (2–82) mm/h and 32.9 (2.1–62.3) mg/dl to 4 (1–10) mm/h and 2.9 (0.2–12.1) mg/dl, respectively (P < 0.001). No TCZ-associated side effects were noted.ConclusionTCZ proved to be safe and effective for refractory arterial lesions in BS, with a steroid- and immunosuppressant-sparing benefit.

A Rare Case of Rheumatoid Arthritis with Tocilizumab-induced Intestinal Mucosal Injury

Intestinal mucosal injury that develops as a complication of tocilizumab (TCZ) is usually associated with diverticulosis. We herein report a rare case of TCZ-induced intestinal mucosal injury in the absence of diverticulosis. A 74-year-old woman suffering from rheumatoid arthritis started taking TCZ. Six months later, she complained of hematochezia and abdominal pain. Colonoscopy revealed multiple ulcers spreading from the cecum to the transverse colon but no diverticulosis. These lesions were cured at three months after the discontinuation of TCZ. We should consider TCZ as a risk factor for intestinal mucosal injury, even if patients have no history of intestinal disease associated with diverticulosis.

Real-world Risk of Relapse of Giant Cell Arteritis Treated With Tocilizumab: A Retrospective Analysis of 43 Patients.

Tocilizumab (TCZ), an interleukin 6 (IL-6) receptor antagonist, is approved for giant cell arteritis (GCA) as a cortisone-sparing strategy and in refractory patients. This study assessed the real-world efficacy, safety, and long-term outcomes of patients with GCA treated with TCZ. We conducted a multicenter retrospective observational study at 3 French centers. All patients aged ≥ 50 years who met the American College of Rheumatology (ACR) criteria, and had received at least 1 dose of TCZ were included. Relapse was defined by therapeutic escalation, such as increased doses of corticosteroids (CS), resumption of CS after weaning, or introduction or intensification of adjuvant therapy. Between 2013 and 2019, 43 patients were included. Patients were followed up for a median 511 days between GCA diagnosis and inclusion, with 34/43 (79%) patients experiencing relapses. At inclusion, median age was 77 years, and median dose of CS was 15 mg/day. After inclusion, the mean cumulative dose of CS was 2.1 g/year vs 9.4 g/year before inclusion (P < 2 × 10-7), with 12/43 (28%) patients experiencing relapses on TCZ. Among 29 patients undergoing TCZ discontinuation, 18 (62%) experienced relapses. Factors associated with relapse after inclusion were introduction of TCZ > 6 months after diagnosis (P = 0.005), absence of ischemic signs at diagnosis (P = 0.006), relapse rate > 0.8/year (P = 0.03), and absence of CS tapering ≤ 5 mg/day (P = 0.03) before inclusion. Serious adverse events occurred in 18/43 patients (42%), including 4 deaths. Our results confirm the effectiveness of TCZ for CS sparing, but after discontinuation of treatment, TCZ allows for a prolonged remission in < 50% of patients. Attention must be paid to the tolerance of this long-term treatment in this elderly, heavily treated refractory population.

Use of 18F-fluorodeoxyglucose positron emission tomography to monitor tocilizumab effect on vascular inflammation in giant cell arteritis.

To evaluate the time-dependent effects of tocilizumab on vascular inflammation as measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in GCA. Patients with GCA treated with tocilizumab were selected from a prospective, observational cohort. Patients underwent FDG-PET at the baseline visit prior to initiation of tocilizumab and at subsequent follow-up visits performed at 6-month intervals. All imaging findings were interpreted blinded to clinical data. The PET vascular activity score (PETVAS) was used to quantify arterial FDG uptake. Wilcoxon signed rank test was used to compare change in PETVAS between visits. Linear regression was used to determine change in PETVAS over multiple timepoints. Twenty-five patients with GCA were included. All patients had physician-determined active vasculitis at the baseline visit by clinical assessment and FDG-PET interpretation. PETVAS was significantly reduced in association with tocilizumab treatment from the baseline to the most recent follow-up visit [24.0 (IQR 22.3-27.0) vs 18.5 (IQR 15.3-23.8); P<0.01]. A significant reduction in PETVAS was observed over a two-year treatment period (P<0.01 for linear trend), with a similar degree of improvement in both the first and second years of treatment. Repeat FDG-PET scans after tocilizumab discontinuation showed worsening PET activity in five out of six patients, with two patients subsequently experiencing clinical relapse. Treatment of patients with GCA with tocilizumab was associated with both clinical improvement and reduction of vascular inflammation as measured by serial FDG-PET. Future clinical trials in GCA should study direct treatment effect on vascular inflammation as an outcome measure.