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Articles

Using Tocilizumab or Sarilumab for hospitalised patients with COVID-19 who are pregnant

12 October 2021A careful risk assessment should be done on the benefits of this off-label use to the mother, and the risks it poses to the fetus or neonate.

Using Tocilizumab or Sarilumab for hospitalised patients with COVID-19 who are breastfeeding

12 October 2021Tocilizumab and sarilumab can be used off-label to treat hospitalised patients with COVID-19. Breastfeeding can continue if these treatments are required.

Providing patient information leaflets following COVID-19 treatment

31 March 2021Following treatment for COVID-19 with tocilizumab, sarilumab, or steroids, clinicians should provide suitable patient information leaflets at discharge

Evidence for use of siltuximab or anakinra as second line therapies (after failure of tocilizumab) for Cytokine Release Syndrome following use of Chimeric Antigen Receptor T-cell (CAR-T) therapy

10 May 2019CAR-T therapy often causes cytokine release syndrome (CRS) which is treated with tocilizumab as first-line therapy. Tocilizumab is licensed for this indication but in some…
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Refrigerated Storage

RoActemraRoche Products Ltd

Roche Products Ltd
RoActemra
162mg pre-filled syringes/pen and 20mg/mL concentrate for solution for infusion

Contact Roche in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.

28 September 2020
London MI Service

Lactation Safety Information

See summary
Very limited published evidence of safety indicates negligible amounts in breast milk, which are likely to be degraded in the infant’s GI tract
Theoretically, absorption may be increased slightly in the neonatal period due to increased gastrointestinal permeability
Negligible infant serum levels and no adverse effects reported to date in infants exposed
Can be used during breastfeeding for patients with COVID-19
Live vaccination does not need to be withheld, unless exposure also occurred during pregnancy
As a precaution, monitor the infant for adequate feeding, fever, frequent infections, diarrhoea, or unusual behaviour
30 November 2021

New Medicines

RoActemra (EU), Actemra (US) Coronavirus disease 2019 (COVID-19)- severe, in hospitalised patients in combination with routine care (e.g. corticosteroids, oxygen, or mechanical ventilation)

Information

RoActemra (EU), Actemra (US)
Licence extension / variation
Roche
Genentech

Development and Regulatory status

Phase III Clinical Trials
Recommended for approval (Positive opinion)
Pre-registration (Filed)
Dec 21EU positive opinion granted recommending a licence change to include use to treat adults with COVID-19 who are receiving systemic treatment with corticosteroids and require supplemental oxygen or mechanical ventilation [29].
Aug 21EMA has started evaluating application to extend use of tocilizumab to include treatment of hospitalised adult patients with severe COVID-19 who are already receiving treatment with corticosteroids and require extra oxygen or mechanical ventilation [28].
Jul 21Roche pipeline now lists tocilizumab (alone, not specifically in combination with remdesivir) as PIII in pipeline; filings planned for 2021 [27]
Jun 21US FDA grants emergency use authorization for tocilizumab in treatment of hospitalized patients aged 2 years and older with COVID-19 who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. EUA is based on data from RECOVERY, EMPACTA, COVACTA and REMDACTA trials [25].
Feb 21Toclizumab monotherapy for COVID-19 no longer listed in company planned filings; filing for combination with remdesvir planned for 2021 [24].
Apr 20Filings planned for 2020 [10].
Apr 20Roche report development will be accelerated following their acceptance of a grant from the U.S. Biomedical Advanced Research and Development Authority (BARDA) [6].
Mar 20China’s National Health Commission added tocilizumab to its updated COVID-19 treatment guidelines following reports of positive outcomes from front line Chinese physicians from its use to control severe lung inflammation in critical care patients [4].

Category

Anti-interleukin-6 (IL-6) receptor monoclonal antibody
Novel coronavirus (2019-nCov) is a new strain of coronavirus first identified in Wuhan City, China in Dec 2019. As a group, coronaviruses are common across the world. Typical symptoms of coronavirus include fever and a cough that may progress to a severe pneumonia causing shortness of breath and breathing difficulties. As of 20 Mar 2020, the WHO reports 209,839 confirmed cases of 2019-nCov globally (81,174 in China), and in the UK the DHSC confirmed 3,269 patients had tested positive [1,2].
Coronavirus disease 2019 (COVID-19)- severe, in hospitalised patients in combination with routine care (e.g. corticosteroids, oxygen, or mechanical ventilation)
Intravenous infusion

Further information

Yes

Trial or other data

Mar 21PIII COVINTOC study in India (n=180) found tocilizumab did not reduce the risk of progression of COVID-19 up to day 14 when compared to standard of care (9% versus 13% respectively; p=0.42) in adults admitted to hospital with moderate to severe COVID-19 [24].
Mar 21PIII COVACTA study (n=452, NCT04320615) published in NEJM [23].
Mar 21Results of REMAP-CAP trial published in NEJM [22].
Feb 21RECOVERY trial demonstrates that tocilizumab reduces the risk of death in hospitalised pts with severe COVID-19 and shortens length of hospital stay and need for ventilation. Pts (n=2022) received i.v tocilizumab + usual care or usual care alone (n=2094) and 82% of pts accross gps were taking a steroid, usually dexamethasone. In the tocilizumab group, 29% of pts died vs. 33% in the usual care only group (RR: 0·86; [95% CI: 0·77 to 0·96; p=0·007), an absolute difference of 4% or NNT of 25 pts treated to save 1 life. Tocilizumab increased probability of discharge within 28 days from 47% to 54% (RR: 1·23, [95% CI 1·12 to 1·34], p<0·0001). These benefits were seen in all subgroups, including those requiring oxygen through to pts ventilated in ITU. In those not ventilated, tocilizumab reduced the chance of progressing to invasive mechanical ventilation or death from 38% to 33% (risk ratio 0·85, [95% CI 0·78 to 0·93], p=0·0005). There was no evidence that tocilizumab had any effect on the chance of successful cessation of invasive mechanical ventilation [26].
Jan 21A Brazilian study (n=129; NCT04403685) was stopped early, as tocilizumab was associated with higher mortality at 15 days versus standard care (component of the primary outcome; 17% v 3%; OR 6.42, 95% CI 1.59 to 43.2), with no clinical benefit noted [21].
Dec 20PIII EMPACTA trial is published; in hospitalised patients with Covid-19 (n=389), the addition of tocilizumab to standard care reduced the likelihood of progression to mechanical ventilation or death by 28 days (12.0% v 19.3%; HR 0.56; 95% CI 0.33-0.97; p=0.04) but did not improve overall survival [19].
Oct 20Cohort study (n=3,924) found those treated with tocilizumab had a lower risk of death vs those not given tocilizumab (HR 0.71, 95%CI 0.56-0.92 after median follow up of 27 days). 30 day mortality was 27.5% for tocilizumab vs 37.1% for no tocilizumab (p<0.05) [18].
Oct 20PII RCT (NCT04346355; n=126) found tocilizumab did not reduce the rate of disease progression (entry to ICU, requirement for mechanical ventilation, death or significant worsening of Pao2/Fio2 ratio) vs placebo in patients with COVID-19 pneumonia and Pao2/Fio2 ratio between 200 and 300 mm Hg [17].
Oct 20PII CORIMUNO-19 RCT (n=131) found that tocilizumab did not improve the rate of reduction of the WHO Clinical Progression Scale score to <5 vs placebo, however fewer patients needed noninvasive or mechanical ventilation or died (24% vs 36%, HR 0.58, 90%CI 0.33-1.00) [16].
Sep 20PIII EMPACTA study met its primary endpoint, showing that patients with COVID-19 associated pneumonia who received tocilizumab plus standard of care were 44% less likely to progress to mechanical ventilation or death compared to patients who received placebo plus standard of care (log-rank p-value = 0.0348; HR [95% CI] = 0.56 [0.32, 0.97]). The cumulative proportion of patients who progressed to mechanical ventilation or death by day 28 was 12.2% in the tocilizumab arm versus 19.3% in the placebo arm [15].
Jul 20In the CHIC study, patients treated with a course of high-dose methylprednisolone plus tocilizumab escalation (days 2-5) if required were more likely to achieve improvement in respiratory status (HR 1.79; 95% CI 1.20-2.67) and on average 7 days earlier than historical controls [12].
Jul 20PII MARIPOSA study (NCT04363736) is recruiting 100 patients and comparing two doses of tocilizumab (8mg/kg and 4mg/kg) plus standard of care. First patient and last patient was enrolled in Q2 20 [14].
Jul 20PIII COVACTA trial (n=330) of tocilizumab in patients hospitalised with severe COVID-19-related pneumonia fails to meet primary end-point of improved clinical status, or key secondary end-point of reduced patient mortality [13].
Jun 20In a study conducted by the Italian drug regulator (n=126) has concluded that tocilizumab did not improve severe respiratory symptoms, reduce ICU visits or reduce mortality rates any more than standard care in patients with early-stage COVID-19 pneumonia [11].
May 20PIII EMPACTA study (Evaluating Minority Patients with Actemra, NCT04372186) initiated. It will evaluate the safety and efficacy of tocilizumab vs. placebo (both with std care) in ~379 pts hospitalised with COVID-19 pneumonia in ~40 facilities accross the US that largely treat minority patient populations. The primary outcome measure is the cumulative proportion of pts requiring mechanical ventilation by day 28 and data are expected in Aug 20. [8,9]
Apr 20Positive results reported from a small French, randomised controlled trial of tocilzumab in 129 pts with moderate to severe COVID-19 penumonia. The trial was conducted by the academic research collaboration COVID-19 Assistance Publique-Hôpitaux de Paris / Universités / INSERM-REACTing. Pts were randomised to receive std treatment + tocilizumab or std treatment only. The primary efficacy endpoint(combination of the need for mechanical or non-invasive ventilation or death on day 14) was achieved in a significantly lower proportion of pts in the tocilizumab arm. The results of this trial are being prepared for submision for publication in a peer-reviewed journal. [7]
Apr 20COVACTA trial (NCT04320615; n=330) has begun recruitment in the US and Europe (UK sites listed but not yet recruiting) [5].
Mar 20Several clinical trials of tocilizumab in treatment of COVID-19 are already underway in China. USTC researchers are running a study comparing tocilizumab with conventional therapy in 188 patients. Another team at Peking University First Hospital is investigating a combination of favipiravir and tocilizumab (NCT04310228; n=150) [4].
Mar 20PIII trial is randomized, double-blind and placebo-controlled (COVACTA) to evaluate the safety and efficacy of intravenous tocilizumab added to standard of care in adult patients hospitalized with severe COVID-19 pneumonia compared to placebo plus standard of care. The primary and secondary endpoints include clinical status, mortality, mechanical ventilation and intensive care unit (ICU) variables. Patients will be followed for 60 days post-randomization, and an interim analysis will be conducted to look for early evidence of efficacy [3].
Mar 20Roche announce initiation of PIII clinical trial in hospitalised patients with severe COVID-19 pneumonia. Enrolment is expected to begin early April with a target of approximately 330 patients globally, including the US [3].

Evidence based evaluations

Tocilizumab biosimilar (BAT1806)Rheumatoid arthritis (RA)

Information

Tocilizumab biosimilar (BAT1806)
Biosimilar
Biogen
Biogen

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Humanised anti-interleukin 6 (IL-6) receptor monoclonal antibody
One UK study found the population minimum prevalence of RA to be 1.16% in women and 0.44% in men [3].
Rheumatoid arthritis (RA)
Subcutaneous injection

Tocilizumab biosimilar (MSB11456) Rheumatoid arthritis (RA)

Information

Tocilizumab biosimilar (MSB11456)
Biosimilar
Fresenius Kabi
Fresenius Kabi

Development and Regulatory status

None
Phase III Clinical Trials
None

Category

A humanised anti-interleukin-6 receptor monoclonal antibody
The prevalence of confirmed RA is about 1% of the UK population. One study in the UK found the population minimum prevalence of RA to be 1.16% in women and 0.44% in men. The incidence of the condition is low, with around 1.5 men and 3.6 women developing RA per 10,000 people per year in the UK [1].
Rheumatoid arthritis (RA)
Subcutaneous injection

RoActemra (EU), Actemra (US) Interstitial lung disease associated with systemic sclerosis

Information

RoActemra (EU), Actemra (US)
Licence extension / variation
Roche
Roche

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Dec 21Roche appears to have no plans to file in the EU or UK for this indication [3-5].
Mar 21The FDA has approved tocilizumab for slowing the rate of decline in pulmonary function in adult patients with systemic sclerosis-associated interstitial lung disease [1]. 08/03/2021 10:09:53

Category

Anti-interleukin-6 (IL-6) receptor monoclonal antibody
SSc affects about 2.5 million people worldwide.4 Interstitial lung disease (ILD), which may occur in approximately 80% of SSc patients, causes inflammation and scarring of the lungs and can be life-threatening [1].
Interstitial lung disease associated with systemic sclerosis
Subcutaneous injection

Trial or other data

May 21Review of the focuSSced RCT (210 patients with early systemic sclerosis) found that, amongst the 136 patients with ILD, tocilizumab demonstrated an improved FVC% preservation than placebo after 48 weeks treatment (-0.1% vs -6.3%) [2].
Mar 21PIII randomised placebo-controlled clinical trial (focuSSced) of 212 adults with systemic sclerosis found patients on tocilizumab had less decline from baseline to week 48 in percent predicted FVC in a post hoc analysis (0.07% vs. -6.4%, mean difference 6.47%), and a smaller decline in FVC compared to placebo (mean change -14 mL vs. -255 mL, mean difference 241 mL) [1].