key: cord-1026097-qyg7vobf
authors: Sharma, Esha; Meade, Susanna; D’Errico, Francesca; Pavlidis, Polychronis; Luber, Raphael; Zeki, Sebastian; Hill, Katie; Duff, Alexa; O’Hanlon, Dearbhaile; Tripoli, Sherill; Stanton, Anna; Caracostea, Andra; Honap, Sailish; Reynolds, Rebecca; Anderson, Simon; Ray, Shuvra; Mawdsley, Joel; Sanderson, Jeremy; Samaan, Mark A.; Irving, Peter M.
title: The effects of COVID‐19 on IBD prescribing and service provision in a UK tertiary centre
date: 2020-12-05
journal: GastroHep
DOI: 10.1002/ygh2.433
sha: 2c3b970d5c10bea0781907af646d1b6093433af8
doc_id: 1026097
cord_uid: qyg7vobf

BACKGROUND: To quantify the effects of COVID‐19 on our inflammatory bowel disease (IBD) unit, including service provision, prescribing practices and use of therapeutic drug monitoring (TDM). METHODS: We performed a single centre retrospective observational cohort study. Data was extracted from our IBD database, electronic patient records and radiology/endoscopy reporting systems between 16/3/20‐17/4/20 and the corresponding period in 2019. RESULTS: A similar number of patients commenced biologic therapy before COVID‐19 (n = 37) and during the pandemic (n = 36). Patients in the pre‐COVID‐19 cohort were older (median 36 vs 29 years, P = 0.009) with a longer median disease duration (9.3 vs 5.2 years, P = 0.02). During COVID‐19 there was a nonsignificant increase in prescribing of vedolizumab (8/37, 22% vs 14/36, 39%, P = 0.13) and a higher proportion of patients were anti‐TNF‐naïve (3/17, 18% vs 18/24, 74%, P = 0.0004). There was a reduction in use of concomitant immunomodulators (22/29, 76% vs 4/34, 12%, P < 0.0001) and increased biologic use in thiopurine‐naïve patients (3/37, 8% vs 15/36, 42%, P = 0.001). Use of TDM fell by 75% (240 vs 59 tests). Outpatient appointments fell by 68% and were conducted via telemedicine. MRI scanning, endoscopy, luminal surgery and inpatient numbers fell by 87%, 85%, 100% and 82% respectively. IBD Clinical Nurse Specialist and Pharmacist helpline contacts increased by 76% and 228% respectively. CONCLUSIONS: We observed prescribing differences during COVID‐19, bypassing the initiation of immunomodulators and/or anti‐TNF therapy in favour of vedolizumab with a reduction in immunomodulator prescribing. We also observed a rapid reorganisation of service provision, including a shift towards telemedicine and online solutions.

The World Health Organisation declared the coronavirus outbreak a pandemic on 11 March 2020. National Health Service (NHS) England subsequently issued a collective plan on 17 March 2020 to all NHS trusts on how to respond to the crisis including cancellation of non-urgent procedures and elective work and staff re-deployment by mid-April. This has had wide-ranging impact across the NHS including on Inflammatory Bowel Disease (IBD) services.

The ever-changing nature of the pandemic, difficulties of remotely delivered care and an overburdened helpline have negatively impacted access to care for IBD patients. This was further exacerbated by a reduction in clinic capacity and delay or cancellation of procedures and investigations. We aimed to quantify the effect of the pandemic on service provision at a tertiary centre.

The risk of COVID-19 is of particular relevance to patients with IBD given a high proportion take therapies that affect the immune system. 

We compared our IBD service provision and prescribing practices between 16 March-17 April 2020 and the corresponding period in 2019. Assessment of service provision and methods for respective data collection are described below.

All patients who were referred to our virtual multidisciplinary biologic and immunomodulator meeting for the treatment of active IBD (identified by abnormal faecal calprotectin, endoscopy or cross-sectional imaging) during the two time periods were included.

Demographic data, previous treatments and treatment decisions were recorded. All patients newly initiated on biologic treatment were discussed at our biologic and immunomodulator meeting. The pharmacy database was reviewed to identify referrals for initiation of thiopurines and methotrexate. 

Clinic codes were used to search Patient Identity Management Service [Custodix NV, Belgium] to calculate the number of patients seen in each clinic.

The numbers of patients starting exclusive enteral nutrition (EEN), taking part in clinical trials, attending the IBD infusion unit, being discussed at multidisciplinary meetings (MDM), or undergoing abdominal surgery and the numbers of inpatients and IBD helpline contacts were extracted from the respective local databases.

To compare the cohorts we used Fisher's exact test for categorical data and Mann-Whitney test for continuous variables. We used descriptive statistics for service provision. Continuous data are presented as medians with ranges in brackets. Analyses were performed using GraphPad Prism v8.4.2.

This work was carried out as part of a service evaluation exercise and therefore, ethical approval was not required. compared to pre-pandemic (19/50 (38%)) (P = 0.01). Change of biologic class, or to tofacitinib, occurred in 7/45 (16%) during COVID-19 compared with 18/50 (36%) pre-pandemic (P = 0.01). The remaining patients were dose escalated on their current therapy or commenced azathioprine alone. Two patients in the pre-COVID-19 cohort were recruited to a clinical trial of an investigational product.

The data for patients commencing biologic therapy or tofacitinib are also shown in Table 2 (n = 37 pre-COVID-19, n = 36 during COVID- 19) . During the pandemic there was a nonsignificant increase in the use of vedolizumab (14/36, 39%), compared to the pre-COVID-19 period (8/37, 22%, P = 0.13). Although treatment escalation to an advanced therapy increased overall, de novo prescriptions for infliximab and tofacitinib fell (14% vs 3%, P = 0.21 and 22% vs 5%, P = 0.10, respectively). Ustekinumab and adalimumab prescribing remained similar. In those patients commenced on vedolizumab or ustekinumab, 18/24 (74%) were anti-TNF naïve compared with 3/17 (18%) before the pandemic (P = 0.004) (Figure 1 ). Across all biologic classes there Differences in the indication for EEN as a treatment for active luminal Crohn's disease were also noted. EEN prescriptions in the pre-COVID-19 cohort were for bridging to vedolizumab (n = 1) and as pre-surgical optimisation (n = 1). In the pandemic cohort EEN was prescribed to enable surgery to be delayed (n = 1), to enable steroid weaning (n = 1) and as an adjunct to medical therapy for symptom management (n = 2). 

Monotherapy, n (%) 0 (0) 1 (100) 0.29

Total n, (%) -UC -CD 

The effects of the pandemic on service provision are shown in Table 3 . Outpatient services were significantly affected during the pandemic with a 68% reduction in appointments, and 100% were conducted via telephone. Prior to the pandemic, only clinical nurse specialist (CNS) and pharmacist appointments were performed telephonically. Conversely, helpline contacts dramatically increased;

there was a 76% increase in contacts to the IBD CNS advice line and a 228% increase in gastroenterology pharmacy helpline contacts ( Figure 2) . A particular surge was noted after the government issued advice on shielding high-risk groups on 16/3/2020.

IBD infusion unit attendances increased, largely due to an increase in vedolizumab initiation. Inpatient numbers were reduced.

Although there was a reduction in the frequency of cross-sectional imaging there was no change in the numbers of patients discussed in the IBD radiology MDM although video conferencing was used to enable social distancing. This is likely due a backlog of MDM referrals and because imaging during COVID-19 was limited to clinically urgent cases where MDM discussion would more often be required. The changes in practice described in this paper largely reflect this advice.

We infection, albeit mainly bacterial. 4, 5 In addition, immunomodulator therapies and tofacitinib are associated with an increased risk of viral infection 6-8 including severe influenza. 9 The concern with regards to increased influenza risk relates to pooled data from the H1N1 epidemic which demonstrated that immunocompromise predicted a more severe disease course. However, these data may not be generalisable to the IBD population nor do they relate specifically RAND panel, it was agreed they were unlikely to be associated with an increased risk of COVID-19 infection or worsening disease course. 18 Moreover, these drug classes have lower rates of immunogenicity compared to anti-TNF therapy so there is less, or no need for concomitant immunomodulation. 19, 20 In addition, adalimumab is delivered subcutaneously thus avoiding the need for hospital attendance and is also less immunogenic than infliximab. 19 These reasons are likely to have led to the increases we observed in use of these agents during the pandemic.

In addition, side effects of therapy may have more significant sequelae during the pandemic and should be considered along with the practicalities of initiating treatments. There are a number of factors that make thiopurine treatment less attractive in the current climate.

Particularly, the intensive blood monitoring required on initiation and risk of adverse effects which may lead to hospitalisation. Both of these factors may increase the risk of nosocomial transmission.

Furthermore, adverse effects such as flu-like syndrome and lymphopaenia may mimic and confuse symptoms and signs associated with SARS-CoV-2 infection. In a recent RAND panel the appropriateness of commencing thiopurine therapy in SARS-CoV-2 negative patients was deemed uncertain for the aforementioned reasons. 21 Our practice reflects these concerns with a substantial decrease in our rate of thiopurine initiation alone or as combination therapy.

Likewise, tofacitinib is associated with a pro-thrombotic risk. 22 Though this complication has not been observed in UC patients and identified in an older cohort of patients with rheumatoid arthritis with at least one cardiovascular risk factor there may have been concerns regarding use of this agent when considered alongside the recognised thrombotic complications associated with Favourable features of tofacitinib, such as its oral administration (thus avoiding hospital visits), rapid onset of action and its short halflife explained our occasional use of this drug. It is also relevant that tofacitinib is being investigated in clinical trials to treat COVID-19

pneumonia, the outcome of which may alter practice. 24 Conversely, concerns about the need for hospital attendance for infusions did not decrease our use of intravenous treatments. There have been variable approaches to this in different units. Our infusion unit is located away from acute areas of the hospital theoretically reducing the risk of nosocomial acquisition of SARS-CoV-2 for attendees. In addition, we were able to continue running our infusion unit at almost full capacity; changes in staffing levels due to redeploy- The COVID-19 pandemic has necessitated a significant shift in our working pattern, most notably the use of telemedicine, enabling us to maintain acute services. There are many obstacles to developing telemedicine services, especially over such an abridged timeframe, but a randomised controlled trial has shown that they reduce hospital visits and IBD admissions compared to standard of care. 30, 31 Whilst remote monitoring may be preferable to some patients, others may prefer, or have symptoms that require, attendance for review or investigation. The pandemic has resulted in a step-change in the use of telemedicine in the UK and as the pandemic subsides, it is likely to remain a significant aspect of future outpatient services.

Finally, the cancellation of large numbers of clinic appointments, investigations, elective imaging and procedures enabled acute services to cope with the influx of patients with COVID-19. However, the huge backlog of work created, and the potential for "collateral damage" to patients who avoided or were unable to access healthcare for non-COVID-19-related issues will undoubtedly affect service provision for months or even years to come. Endoscopy in particular, since it is an aerosol generating procedure, remains hugely problematic with most units only just beginning to resume services, initially, with a significant reduction in capacity in most cases. 1

This study builds upon our existing understanding of the impact that COVID-19 has had on IBD services in the UK. That knowledge, largely based upon a survey of IBD clinician opinions towards the beginning of the pandemic, 25 has been corroborated and added to here, through the collection of data relevant to IBD clinical management and service provision. These aspects should be considered strengths of this study and may be considered helpful in planning service recovery. However, our study also has limitations. Most notably, its retrospective nature in a single centre with a relatively small sample size. In addition, due to the lack of data regarding COVID-19, the changes in prescribing habits described here were largely made on an empirical basis and before the development of national guid- To conclude, we observed alterations in prescribing habits during the COVID-19 pandemic that often included bypassing immunomodulators and/or anti-TNF therapy in favour of vedolizumab and greater use of monotherapy. We also observed a rapid reorganisation of service provision that included a shift towards telemedicine and online solutions. Follow-up studies are essential to understand the impact of these changes on patient outcomes and are currently being planned.

The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to. No ethical approval was required as this work was carried out as part of a service evaluation exercise. 

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