Vol. 137 No. 1598 |

DOI: 10.26635/6965.6613

Modern paradigms in biologic sequencing of inflammatory bowel disease in Aotearoa New Zealand

Moderate-to-severe IBD represents a group of patients at risk of poorer outcomes. Mounting evidence suggests biologic and small molecule medications, collectively termed advanced therapies, are the most effective tools clinicians possess, and many societal guidelines recommend their early deployment to achieve best outcomes.

Full article available to subscribers

The modern treatment of inflammatory bowel disease (IBD) has evolved significantly in recent years. This includes development of new pharmacologic therapies for disease control, and their implementation in clinical practice. Moderate-to-severe IBD represents a group of patients at risk of poorer outcomes. Mounting evidence suggests biologic and small molecule medications, collectively termed advanced therapies, are the most effective tools clinicians possess, and many societal guidelines recommend their early deployment to achieve best outcomes.1–4

Even with biologic treatment, many patients do not respond or lose response over time, termed primary non-response (PNR) and loss of response (LOR), respectively.5,6 Until recently, most randomised trials demonstrating efficacy and safety of biologics have been placebo-controlled, with a lack of head-to-head studies and active comparators.7 Therefore, selecting the right medication for the appropriate clinical scenario can be difficult, and is not guided by high-quality prospective comparative data. In addition, there is emerging evidence of differing clinical success when positioning biologic treatments in different sequences.8–11 This is important, as one-third of patients treated with biologics will require a switch to a second agent by 12 months, and a further 20% will require a third agent.12 The optimal sequence to treat patients is currently supported by network meta-analyses, real-world studies and expert opinion.13

Over the years, there have been widespread calls in Aotearoa New Zealand (New Zealand) for increasing biologic treatment options for IBD beyond anti-tumour necrosis factor alpha inhibitors (anti-TNFs). Ustekinumab (UST) and vedolizumab (VDZ) received public funding for the treatment of moderate-to-severe IBD in February 2023, and this has presented long-awaited opportunities for IBD patients, but also new challenges for clinicians in regard to treatment selection. There is significant regional variation in expertise across New Zealand, and in some centres, general physicians and surgeons manage IBD rather than specialist gastroenterologists.14 The purpose of this document is to provide guidance to clinicians on biologic selection and sequencing in patients with moderate-to-severe disease. These recommendations are specific to the New Zealand prescribing climate, supported by the best available evidence, and endorsed by the New Zealand Society of Gastroenterology IBD Working Group through consensus voting.

Individualising biologic treatment selection

In adult patients with IBD, medication selection may be informed by patient, disease, drug and/or systemic factors. The relevant patient factors include age, comorbidities, preferences and impact on whānau and lifestyle—each requiring balanced consideration. Secondly, disease behaviour, such as presence of fistulising disease, inflammatory burden and/or extra-intestinal manifestations may influence treatment selection. Thirdly, drug factors must be considered, such as speed of onset, efficacy, safety, adverse effects, mode of administration and risks of immunogenicity, the latter specifically influencing immunomodulator (IM) co-prescription. Responsible prescribing means clinicians also need to understand system factors, such as costs of medicines, demands on infusion centres and local drug availability.

New Zealand continues to have restricted access to biologics, including to biosimilars beyond Amgevita (adalimumab). Biosimilar therapies are manufactured medications that have virtually indistinguishable properties to their originators but offered at significant cost discounts.15 PHARMAC is the national drug-purchasing agency, which has governance over special authority criteria designed to minimise healthcare expenditure. Understanding these criteria is fundamental to prescribing in New Zealand.16 While allocation of limited healthcare resource is important, medication costs also need to be balanced against costs of persisting disease activity and healthcare utilisation from sub-optimally treated patients.17 It is notable, for example, that small molecule advanced therapeutics are not currently funded in New Zealand.

Moderate-to-severe ulcerative colitis

The therapeutic approach to moderate-to-severe ulcerative colitis (UC) has evolved to favour advanced therapies, as these patients have a more aggressive disease course and higher likelihood of requiring hospitalisation or colectomy. This is reflected in international guidelines such as those published by the American Gastroenterological Association recommending early use of biologic agents over step-up treatment.3 Biologics have advantages over alternatives in terms of superior efficacy, more rapid effect onset and flexibility with individualised dose optimisation.18–20 These guidelines define moderate-to-severe UC as a Mayo score of 6 or above with endoscopic sub-score of 2 or above, and/or patients who are dependent or refractory to corticosteroid treatment.

The suggested biologic sequence for moderate-to-severe UC is summarised in Table 1. This sequence is unique to New Zealand in the context of current PHARMAC reimbursement criteria (at time of publication).

1. Biologic-naïve UC and first-line therapies

For patients with moderate-to-severe biologic-naïve UC, we recommend vedolizumab (VDZ) or infliximab (IFX) for first-line use, favouring VDZ in most cases. IFX will be most familiar to local clinicians and has faster speed of onset. It is also the only approved biologic in acute severe ulcerative colitis (ASUC). However, VDZ is safer, has superior treatment persistence data and overall may be better as a first-line choice in the majority.21–23 Several past studies, including network meta-analyses by Singh et al. showed comparable efficacy between these agents, but due to its relative novelty, long-term data on VDZ is still emerging.24–29

1.1 Vedolizumab (VDZ)

Vedolizumab (VDZ) is an IgG1 monoclonal antibody that binds to the α4β7 integrin on T cells. This integrin mediates lymphocyte migration within gut mucosa and its blockade produces a gut-selective, anti-inflammatory effect.30 The advantage of this mechanism of action is in the preservation of normal systemic immunity.30 VDZ is therefore an attractive option in patients at risk of immunosuppressive (IS) adverse events, including elderly populations and those with comorbidities.31 The favourable safety of VDZ was published in the landmark GEMINI randomised trials, which demonstrated comparable adverse events to placebo.32

There are no prospective, head-to-head, randomised controlled trials comparing VDZ and IFX in UC, but there are a few high-quality retrospective and real-world studies to draw conclusions from. In a large United Kingdom (UK) cohort study, 13,222 patients with biologic-naïve UC treated with VDZ were compared with IFX and 5-year drug effectiveness was superior for VDZ (p=0.006).23 Likewise, in the VEDOIBD registry, 512 patients in multiple centres across Germany had superior long-term clinical remission when initially treated with VDZ versus anti-TNF (43.2% VDZ vs 25.8% anti-TNF, p <0.011).21 A large American database study also found higher treatment persistence with VDZ at both 12 months (84.5% VDZ vs 77.5% IFX) and 24 months (77.6% VDZ vs 64.6% IFX).33

VDZ has a relatively long half-life of up to 26 days, which means it may take 3 months before reaching steady state concentrations and maximal therapeutic effect.34 Initial response can be seen within 2 weeks, but concurrent induction with corticosteroids may need to be considered.35,36 VDZ can be dose intensified and given every 4 weeks in the setting of LOR.37 This is not currently funded in New Zealand, but can be obtained via application for compassionate supply from the manufacturer.

In regard to immunogenicity, anti-drug antibodies (ADAbs) are rare and occur in around 4% of patients treated with VDZ.38 Concomitant IMs may only reduce this risk by a small margin and therefore VDZ is recommended as monotherapy, especially when being used first-line.39 In select patients with severe disease already established on IMs, we recommend review of combination therapy on a case-by-case basis. Overall, with respect to safety, rates of long-term remission, treatment persistence and advantages of monotherapy, VDZ is ideally positioned as a first-choice option for biologic-naïve UC.

1.2 Infliximab (IFX)

Infliximab (IFX) is a chimeric anti-TNF that blocks the interaction between TNFα and its receptor. This prevents activation of multiple downstream inflammatory cascades with a rapid onset of action.40 This rapidity makes IFX particularly useful as a steroid-sparing agent for induction of remission.40 In the meta-analysis by Trigo-Vicente et al., IFX demonstrated greater efficacy with induction compared with VDZ (OR: IFX 4.15 vs VDZ 3.7).26

IFX should be prioritised as first-line therapy when a rapid response is required or where there is significant extra-intestinal disease. Currently, IFX is the only biologic approved for use in ASUC.41 In patients with extra-intestinal manifestations (EIM), particularly arthropathies, ocular manifestations and IBD-related skin disease, the anti-TNF therapies carry the most evidence and are most efficacious.42,43

As IFX contains a murine (mouse-derived) drug component, it is more immunogenic than other biologics and therefore immunomodulator co-prescription is generally recommended to preserve drug levels, especially during the first year of therapy.44 In the setting of low drug titres, dose escalation or shortening of the dosing interval is warranted, although this is limited in New Zealand under current funding models.45 A meta-analysis of 41 included studies showed that 5–50% of all induced patients required dose escalation, and 15–70% of initial responders required subsequent dose escalation within the first year.46 Furthermore, longitudinal studies have shown that rates of required dose escalation probably increase with time.47 Subcutaneous (SC) biosimilar IFX is not currently available in New Zealand, but has advantages of a more stable pharmacokinetic profile and reduced rates of ADAbs.48 Variation in access to infusion centres across New Zealand may also make SC delivery more equitable. The availability of SC biosimilar IFX may alter the sequencing landscape when approved.

1.3 Adalimumab (ADA)

Adalimumab (ADA) is a recombinant human anti-TNF that is administered subcutaneously. While this is convenient for administration, it is not as effective as VDZ or IFX for biologic-naïve UC.49,50 The VARSITY trial is one of a few randomised head-to-head trials comparing efficacy of VDZ with ADA.50 In the sub-group analysis of biologic-naïve patients, ADA showed inferior rates of clinical remission, mucosal healing and histologic remission after 1 year.50 ADA was also inferior to IFX at reducing hospitalisation in a nationwide, propensity-matched study from Denmark.49

One of the reasons that ADA might be selected in UC is patient preference for self-administered SC injection over IV infusion in terms of lifestyle and avoiding time at infusion centres.51 Dose intensification to weekly administration should be considered following LOR and is reimbursed through PHARMAC.

The only biosimilar currently available in New Zealand is Amgevita, which has largely replaced Humira, the originator ADA biologic. Biosimilars have significant healthcare cost advantages, so for patients with milder UC phenotypes, in spite of its lower efficacy, Amgevita might be considered as an alternative first-line agent, prioritising patient preference and healthcare savings.52 This recommendation will likely change with introduction of the aforementioned SC IFX biosimilars and/or SC VDZ.

1.4 Ustekinumab (UST)

Ustekinumab (UST) is currently reserved for biologic-exposed patients under New Zealand special authority criteria. UST is an IgG1 monoclonal antibody that antagonises interleukin-12 and interleukin-23. These cytokines share a p40 subunit which, when blocked, inhibits natural killer (NK) cell and T cell mediated inflammation.53 Following IV induction, UST is given as a SC maintenance therapy, making it the only other SC agent available. Immunogenicity is rare, with reported rates of 2.9% in CD and 4.6% in UC after 1 year.54,55 Concomitant IMs do not appear to modify this risk or improve efficacy; therefore, cessation of IMs should be considered in most patients.56

2. Biologic-exposed UC and sequencing

2.1 Dose optimisation and therapeutic drug monitoring (TDM)

Dose optimisation and countering immunogenicity should be considered prior to switch of biologic therapy. In the modern era, this is increasingly guided by therapeutic drug monitoring (TDM), with evidence to support a TDM strategy being most robust for the anti-TNF biologics. This is especially true for IFX, where there is a clear correlation between drug trough levels and clinical efficacy.57 PNR or LOR should prompt an assessment of treatment adherence, and measurements of drug concentrations and anti-drug antibodies. This can guide decisions regarding dose escalation, addition of concomitant therapy and switching within- or out-of- biologic class.58,59 The evidence for dose optimisation of UST and VDZ based on TDM remains at a nascent stage.60

While there are no prospective studies validating a proactive TDM approach, these concepts are relevant given the limited landscape of treatments within New Zealand and diminishing effectiveness with sequential lines of therapy.61

2.2 Non-response to biologics

Non-response to VDZ—switch to IFX or UST

In the setting of non-response to VDZ, we recommend switching to either IFX or UST as second-line agents. Neither of these have been shown to have reduced efficacy following anti-integrin (VDZ) use and, in fact, there might be higher activation of TNF signalling in VDZ non-responders.62 This further supports the early positioning of VDZ in the sequence of biologic treatments for UC, in order to preserve subsequent biologic choices.61

Non-response to anti-TNFs—switch to UST

In patients who do not respond to first-line anti-TNFs, we recommend a switch to UST as the best sequencing option. Multiple studies have shown that prior anti-TNF exposure can negatively impact likelihood of subsequent response to a second-line biologic agent. This is true of VDZ, ADA and ozanimod, which were studied in GEMINI, VARSITY/ULTRA II and True North respectively.50,63,64 It has been theorised that non-responders to anti-TNFs may upregulate IL-23 that becomes resistant to apoptosis, so blockade of these receptors forms the mechanistic theory of preserved UST effect.65,66

In the UNIFI trial, UST was compared with placebo for both biologic-naïve and biologic-exposed patients, with the majority of the latter group having previously been treated with anti-TNFs. On sub-group analysis, rates of remission between biologic-naïve and exposed groups were comparable, with only minimal differences in clinical response and mucosal healing.53 TORUS is a recently published multi-centre, real-world study that sought to corroborate these findings. The authors highlighted some negative exposure effects, particularly in the setting of more than one prior biologic failure (OR, 2.88; 95% CI, 1.20–6.98); however, the magnitude of difference was less for UST than other cited studies involving different biologics.67 Dose intensified UST is not currently funded in New Zealand but can be obtained for off-label use via application for compassionate supply from the manufacturer.

With VDZ use in biologic-exposed patients, the prior exposure effects are more pronounced. A clinical response of 53.1% was demonstrated in anti-TNF-naive patients versus 39.0% in anti-TNF-exposed patients. There were also significantly worse outcomes in rates of clinical remission (23.1% vs 9.8%) and mucosal healing (49.2% vs 30.5%).68

In any case, non-response to anti-TNF therapy should be considered a predictor of treatment-resistant disease, with these patients significantly less likely to respond to a second-line biologic. A systematic review and meta-analysis of IBD patients who stopped their anti-TNF due to PNR demonstrated a 24% lower likelihood of achieving remission with another biologic compared with those who stopped due to intolerance (RR of remission—0.76 [0.61–0.96]).5

3. Third-line biologics for UC and beyond

When attempting to recapture remission with third-line biologics, consideration needs to be made for the overall trajectory of the patient and the predicted likelihood of success with additional conventional therapies. As mentioned, there is negatively correlated clinical efficacy with increasing numbers of biologic exposures, so alternative approaches should be considered.

3.1 Clinical trials

Clinical trials are a fundamental component of the modern treatment armamentarium, as they allow patients’ access to novel therapies. Most current biologic trials are designed with several active treatment arms, as well as continued access through long-term extensions. Clinical trials should be considered for all suitable IBD patients to widen therapeutic access, especially in those with moderate-to-severe disease. There are initiatives within Health New Zealand – Te Whatu Ora that aim to improve regional access to clinical trials and better coordinate IBD care. Centres without specific trial coordinators should be aware which sites have access and refer appropriately.

3.2 Janus Kinase (JAK) inhibitors

JAK inhibitors are small molecules that block tyrosine kinases, responsible for intra-cellular transmission of inflammatory signals.69 Within T cells, JAK-STAT signalling triggers differentiation into T helper cells, which have a key role in mediating the inflammatory response in IBD.70 The landmark OCTAVE trials demonstrated clinical efficacy of JAK inhibitors in both biologic-naïve and biologic-experienced patients, and this has been confirmed with large, real-world systemic reviews/meta-analyses.71,72

Differing from the monoclonal antibody biologics, these small molecules are administered orally, have a rapid onset of action, are non-immunogenic and also non-specific in their effect, therefore carrying the potential to block multiple inflammatory pathways simultaneously.73 The rapid onset of action and high bioavailability have led to their consideration as an adjunctive treatment in ASUC.74,75

These are not currently funded in New Zealand for IBD but are being considered by authorities and will be highly ranked in treatment algorithms once approved. These will be especially valuable treatments for biologic-experienced patients once available.

3.3 Colectomy

Colectomy should be considered in biologic-refractory patients, especially those approaching third-line biologics. In patients who have exhausted IFX and UST, this needs to be strongly considered due to the aforementioned attenuated effect of ADA and VDZ in the biologic-experienced cohort. Surgery offers a cure for UC and obviates the need for maintenance therapies and surveillance of dysplasia. We recommend early involvement of a colorectal surgeon and multi-disciplinary discussion alongside patients in this setting.

Moderate-to-severe Crohn’s disease

Crohn’s disease (CD) is a chronic inflammatory disease which, unlike UC, has no surgical cure in treatment-refractory cases. Complications of CD can be severe, including intestinal stricturing, obstruction, fistulae, abscesses, hospitalisation and surgery.76 Tight disease control is therefore mandatory to prevent morbidity. This involves regular clinical assessment and early escalation to biologic therapy, especially in moderate-to-severe disease and those with phenotypic risk factors including deep ulceration, strictures, extensive or fistulising disease.

There are drawbacks to using symptom-based scoring systems in CD, where clinical presentations may be heterogeneous, and morbidity may arise from untreated sub-clinical disease. Modern paradigms in disease assessment preference composite metrics of disease activity, including measurement of biomarkers, and we suggest this approach when determining best treatment strategies.77 These guidelines define moderate-to-severe luminal CD as patients with a CD activity index of 220 or above, those who are dependent or refractory to corticosteroid treatment, or those with phenotypic risk factors, such as large or deep mucosal lesions on endoscopy.

The suggested biologic sequence for CD is summarised in Table 2. This sequence is unique to New Zealand in the context of current PHARMAC reimbursement criteria (at time of publication).

1. Biologic-naïve CD and first-line therapies

Luminal CD

As with UC, biologic selection should be personalised based on disease characteristics, patient factors and preferences, as well as access and systemic factors. In biologic-naïve luminal CD, anti-TNF agents are generally the preferred first-line choice.

1.1 Anti-TNF therapy (ADA or IFX)

Multiple studies support use of both ADA or IFX in induction and maintenance settings.78,79 There is currently no head-to-head data comparing these two choices and real-world studies provide conflicting evidence. Some meta-analyses suggest comparable efficacy, whereas others demonstrate slight superiority of IFX.23 This difference may be adjusted when considering combination therapy with IMs. For example, on the basis of 15 randomised controlled trials and 2,931 enrolled patients, different biologics were compared with certolizumab pegol in a meta-analysis. IFX plus azathioprine (OR 7·49 [2·04–27·49]) and IFX monotherapy (OR 4·53 [95% CI 1·49–13·79]) were both superior to ADA monotherapy (OR 3·01 [1·25–7·27]) and ustekinumab monotherapy (OR 2·63 [1·10–6·28]).4

In the absence of robust head-to-head data, either anti-TNF selection is appropriate first-line. ADA carries the advantages of self-administration and cost savings, whereas IFX has the advantage of greater capability with dose escalation, which can be attractive in difficult-to-treat disease. IM co-prescription should be considered to prevent ADAbs, with IFX being particularly immunogenic.

1.2 Vedolizumab (VDZ)

VDZ may not be as efficacious as the anti-TNF agents for luminal CD with lower surface under the cumulative ranking (SUCRA) probabilities in network meta-analyses.80 However, there is development of a validated clinical decision support tool (CDST) to predict which patients may be more likely to respond to VDZ treatment.81 These tools are not yet routinely utilised in clinical practice, but may help select patient profiles appropriate for first-line VDZ. At this stage, VDZ would be considered a first-line alternative in those with a milder disease phenotype or in the co-morbid patient, especially due to its safety advantages.

1.3 Ustekinumab (UST)

In New Zealand, UST is reserved for biologic-exposed patients under special authority criteria. However, there is mounting evidence to support its use in the biologic-naïve setting, and this is a trend observed internationally due to its efficacy, subcutaneous administration, lack of immunogenicity and superior treatment persistence. The SEAVUE study was a multi-centre, randomised, double-blind, active comparator trial in biologic-naïve patients with CD. This showed no significant difference in efficacy between ADA (61%) and UST (65%) in remission rates at 12 months.82 This is supported by 10-year national data from South Korea showing superior treatment persistence with UST compared to IFX (adjusted hazard ratio [aHR] 0.69, p=0.048).83 While UST would be an attractive first-line treatment for luminal CD, this is not currently funded.

2. Fistulising CD


The majority of fistulising CD involves perianal fistula, which can occur in up to one-third of CD patients.84 Luminal fistulising CD is also observed, which can form between one loop of bowel and another (enteroenteric), from bowel to bladder (enterovesicular), vagina (enterovaginal) or skin (enterocutaneous), posing a substantial burden on physical, social and emotional wellbeing. The presence of fistulising perianal or luminal disease establishes a severe phenotype that signals the need for biologic treatment. It is noteworthy that fistulising CD is one of the only indications in New Zealand where anti-TNF therapies are funded regardless of symptoms and previous treatment exposure.

The majority of published studies on drug therapies in fistulising CD apply to outcomes for perianal disease, with more limited data on luminal fistulae. Recommendations from this guideline have been made based on best available evidence for perianal CD, with the extrapolation that a similar response to therapy is likely observed in other forms of fistulae.

Anti-TNFs are the preferred treatment in this setting, with IFX the only evidence-based biologic. This was demonstrated in a large, dedicated, randomised, placebo-controlled trial that showed a 69% response rate following induction, with sustained results at 1 year (IFX 46% vs placebo 23%, p=0.001).85 While there is some data supporting the use of ADA, VDZ and UST in fistulising disease, the evidence is less robust, and IFX should be considered first-line, especially for complex fistulae.86

Surgical management is outside the scope of this article, however there is evidence for improved outcomes with combined surgical and medical management in complex fistulising CD.

3. Biologic-exposed CD and sequencing

3.1 Non-response to anti-TNF—switch to UST

Primary non-response to an anti-TNF agent occurs in up to 24% of CD patients within 3 months of commencing treatment.87 Various factors including disease duration, disease phenotype, body mass index (BMI), prior surgery and smoking status have been implicated.88 In this setting, sequential use of another anti-TNF is fraught, with a recaptured remission rate of only 30%. This is compared with over 60% when the reason for switching medication is intolerance.89

Therefore, in PNR we recommend switching out-of-class to UST. Similar to UC, UST efficacy in CD is not affected by prior anti-TNF exposure, possibly due to IL-23 up-regulation.90–92 However, the same is not true of VDZ.93,94 Comparing real-world data, there is superior treatment persistence with second-line UST (79.2%) compared with VDZ (54.9%).83 When deploying VDZ in bio-exposed patients, we suggest a low threshold for consideration of an additional week 10 dose via individual application for compassionate supply from the manufacturer.

3.2 Loss of response to anti-TNF—dose escalate before switch to UST

Loss of response to anti-TNF therapy is a common issue and occurs in 23–46% of CD patients, with a 13% per patient-year risk.88 This is frequently driven by low drug levels and/or immunogenicity.95 As discussed within the UC section, we recommend application of TDM principles and dose optimisation to attempt to recapture response as the first countermeasure. The randomised ACCENT I study showed that 90% of patients who lost response to 5mg/kg IFX restored response after an escalation in dose to 10mg/kg.96 Furthermore, almost 80% of patients who had LOR to 10mg/kg dosing regained response after another dose escalation to 15mg/kg.96 Reducing the interval between doses has a similar effect, with a multi-centre Spanish study demonstrating 83% of patients regaining response with 4-weekly dosing.97 The presence of high anti-drug antibody titres is the primary caveat to this intensification approach, with a 90% specificity for subsequent treatment failure.98

4. Third-line biologics for CD and beyond

As with UC, there is reduced clinical efficacy with increasing number of biologic exposures, and alternative approaches, such as enrolment in clinical trials, should be considered to advance access to unfunded medications. There is very promising data overall for JAK inhibitors, especially upadacitinib (UPA), in this cohort of medication-refractory patients and regulatory approval is eagerly awaited. We support multi-disciplinary involvement of specialist nurses, gastroenterologists and surgeons in challenging cases.


Selecting the optimal biologic treatments through the chronic, relapsing course of IBD continues to be a challenge for clinicians and patients alike. Navigating this skilfully requires proactive disease assessments, therapeutic drug monitoring and attention towards expanding evidence surrounding biologic sequencing. This is a dynamic and rapidly evolving field, and recommendations will change both with emerging evidence as well as advances in national funding and medication access. We present an overview of the current evidence in this space, which aims to function as a practical and useful guide to clinicians caring for patients afflicted by these diseases.

View Table 1–2.

The modern treatment of inflammatory bowel disease (IBD) has evolved significantly in recent years. This includes development of new pharmacologic therapies and their implementation in clinical practice. Moderate-to-severe IBD represents a group of patients at risk of poorer outcomes, and mounting evidence suggests biologic and small molecule medications, collectively termed advanced therapies, are the most effective tools clinicians possess.
Even with biologic treatment, many patients do not respond or lose response over time. Until recently, most randomised trials demonstrating efficacy and safety of biologics have been placebo-controlled with a lack of head-to-head studies. Therefore, selecting the right medication for the appropriate clinical scenario can be difficult. In addition, there is evidence of differing clinical success when positioning biologic treatments in different sequences. This is important, as one-third of patients treated with biologics will require a switch to a second agent by 12 months, and a further 20% will require a third agent.
Over the years, there have been widespread calls in Aotearoa New Zealand for increasing biologic treatment options. Ustekinumab and vedolizumab received public funding for the treatment of moderate-to-severe IBD in 2023, and this has presented long-awaited opportunities for patients, but also new challenges for clinicians in regard to treatment selection. The purpose of this document is to provide guidance to clinicians on biologic selection, sequencing and optimisation for IBD. These recommendations are specific to the domestic prescribing climate, supported by the best available evidence and endorsed by the New Zealand Society of Gastroenterology IBD Working Group.


Dr Michael Chieng, MBChB: Department of Gastroenterology, Waikato Hospital, Pembroke Street, Hamilton, New Zealand; Faculty of Medicine, The University of Auckland, Park Road, Auckland, New Zealand.

Dr Bronson Marshall, MBChB: Department of Gastroenterology, Wellington Hospital, Riddiford Street, Wellington, New Zealand.

Dr Caroline Jiang, MBChB, FRACP: Department of Gastroenterology, Wellington Hospital, Riddiford Street, Wellington, New Zealand.


Dr Michael Chieng: Gastroenterology Department – Waikato Hospital, 183 Pembroke Street, Waikato Hospital, Hamilton 3204, New Zealand. Ph: +64 21 212 258.

Correspondence email

Competing interests

CJ has received speaker fees from Takeda, Janssen, Abbvie.

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