Infliximab biosimilar GP1111: a review of 5 years’ post-approval experience

Figures & data

Table 1. Guideline recommendations for the use of infliximab across the approved indications.

Disease	EU recommendation	US recommendation	References
RA	The addition of bDMARDs such as infliximab is recommended if the treatment target is not achieved with 1 L MTX and poor prognostic factors are present (SoR: A) bDMARDs can also be combined with a conventional synthetic DMARD (SoR: A)	In patients with inadequate response to 1 L MTX, the addition of bDMARDs such as infliximab is recommended over triple therapy (CoE: very low)	EU: [8] US: [9]
Adult CD	In adults with moderate-to-severe CD: Induction: combination therapy with a thiopurine is recommended when starting infliximab to induce remission in those having had an inadequate response to conventional therapy (SoR: strong) Remission: TNFis (e.g. infliximab) are recommended in those who have not responded to conventional therapy (SoR: strong) Maintenance: infliximab monotherapy can be used in those achieving long-term remission using infliximab plus immunosuppressants (SoR: weak) Complex perianal fistulizing disease: infliximab is recommended for the induction and maintenance of remission (SoR: strong)	In severe/fulminant disease: TNFis (e.g. infliximab) can be considered to treat severely active CD (SoR: strong) Infliximab may be administered to treat fulminant CD (SoR: conditional) In moderate-to-severe luminal and perianal fistulizing CD: Induction and maintenance of remission: the use of TNFi is recommended over no treatment (SoR: strong) Induction of remission in biologic-naïve outpatients: infliximab, adalimumab, and ustekinumab are recommended over certolizumab pegol (SoR: strong, conditional) Induction and maintenance of remission in biologics and immunomodulator-naïve outpatients: infliximab combined with thiopurines is recommended over infliximab monotherapy (SoR: conditional) Induction and maintenance of fistula remission in outpatients with CD and active perianal fistula: infliximab is recommended over no treatment (SoR: strong)	EU: [10] US: [11,12]
Pediatric CD	TNFi is recommended for: Inducing and maintaining remission in children with chronically active luminal CD despite prior optimized immunomodulator therapy (100% agreement) Inducing remission in children with active steroid-refractory disease (100% agreement) Primary induction and maintenance therapy for children with active perianal fistulizing disease in combination with appropriate surgical intervention (84% agreement) Maintaining remission using regularly scheduled treatment in children responding to induction therapy with TNFi (100% agreement)	In children with perianal CD: Simple perianal fistula without inflammation, and complex perianal fistula with/without inflammation: antibiotics, immunomodulators, and TNFi (no grading of recommendation given) Deep perianal abscesses: surgical drainage followed by treatment of intestinal disease with TNFi (no grading of recommendation given)	EU: [13] US: [14]
Adult UC	TNFi (e.g. infliximab) is recommended for: Inducing remission in patients with moderate-to-severe Maintaining remission in patients with UC who responded to induction therapy with the same medicine (SoR: strong)	In adults with moderate-to-severe UC: In adult outpatients: infliximab, adalimumab, golimumab, vedolizumab, tofacitinib, or ustekinumab are recommended over no treatment (SoR: strong) Induction of remission in biologic-naïve outpatients with UC: use infliximab or vedolizumab rather than adalimumab (SoR: conditional) In hospitalized adult patients with acute severe UC refractory to IV CS: use infliximab or cyclosporine (SoR: conditional) In hospitalized adult patients with acute severe UC being treated with infliximab: no recommendation on routine use of intensive versus standard infliximab dosing	EU: [15] US: [16]
Pediatric UC	In TNFi-naïve children for whom IV CS treatment fails: 2 L infliximab is recommended (100% agreement) In children responding to infliximab commenced during acute severe UC: continue infliximab as maintenance treatment following discharge (100% agreement)	No US pediatric guidelines identified However, NASPGHAN training documents refer to ECCO/ESPGHAN 2018 guidance	EU: [17] US: [18]
AS	In patients with persistently high disease axial activity despite conventional treatments: consider TNFi, anti-IL-17, or JAK inhibitors (SoR: A) Following first failure with b/tsDMARD: consider switching to another bDMARD or JAK inhibitor (e.g. TNFi after TNFi; SoR: B) During sustained remission: consider tapering bDMARD (e.g. TNFi) (SoR: B)	In adults with active AS despite treatment with NSAIDs: Strongly recommend TNFi over no treatment with TNFi (PICO 6); do not recommend any particular TNFi (PICO 5) Conditionally recommend TNFi over treatment with secukinumab or ixekizumab (PICO 59), or tofacitinib (PICO 60) In adults with active AS despite treatment with the first TNFi used: For secondary non-response to TNFi: conditionally recommend treatment with a different TNFi versus a non-TNFi biologic (PICO 10) Strongly recommend against switching to a biosimilar of the first TNFi (PICO 62) In adults with stable AS receiving treatment with a biologic (e.g. TNFi): Conditionally recommend against discontinuation of the biologic (PICO 66) Conditionally recommend against tapering of the biologic dose as a standard approach (PICO 65) In adults with stable AS receiving treatment with TNFi and NSAIDs or a conventional synthetic DMARD: Conditionally recommend continuing treatment with TNFi alone over TNFi plus NSAIDs (PICO 11) or conventional synthetic DMARD (PICO 12) In adults with stable AS on reference TNFi: Strongly recommend continuing treatment with the reference TNFi over mandated switching to its biosimilar (PICO 63) In adults with AS and recurrent uveitis or IBD: Conditionally recommend treatment with TNFi monoclonal antibodies over treatment with other biologics (recurrent uveitis, PICO 29; IBD, PICO 32)	EU: [19] US: [20]
PsA	In patients with active predominantly axial disease and insufficient response to NSAIDs: Therapy with a bDMARD should be considered, which according to current practice is a TNFi (SoR: B) In patients who do not adequately respond to, or are intolerant of, a bDMARD: Switching to another bDMARD should be considered, including one switch within a class (SoR: C) In patients in sustained remission, cautious tapering of DMARDs may be considered (SoR: C)	In oral small molecule* and other treatment-naïve patients with active PsA: Conditionally recommend treating with TNFi versus oral small molecules* (PICO 10a – e), anti-IL-17 (PICO 14), or anti-IL-12/23 (PICO 13) In adult patients with active PsA despite treatment with an oral small molecule* [22]: Conditionally recommend switching to a TNFi over a different oral small molecule (PICO 23), anti-IL-17 (PICO 17), anti-IL-12/23 (PICO 16), abatacept (PICO 67), tofacitinib (PICO 76), or MTX and TNFi combination therapy (PICO 19) In adult patients with active PsA despite TNFi monotherapy: Conditionally recommend a different TNFi over switching to anti-IL-17 (PICO 28), anti-IL-12/23 (PICO 27), abatacept (PICO 70), tofacitinib (PICO 73), or MTX and TNFi combination therapy (PICO 30) Conditionally recommend a different TNFi (with or without MTX) over adding MTX to the same TNFi (PICO 26 and 26A) In adult patients with active PsA despite treatment with MTX and TNFi combination: Conditionally recommend switching to a different TNFi plus MTX over switching to a different TNFi monotherapy (PICO 33) In adult patients with active PsA despite treatment with anti-IL-17 monotherapy: Conditionally recommend switching to TNFi over an anti-IL-12/23 (PICO 39), a different anti-IL-17 (PICO 42), or over adding MTX to anti-IL-17 (PICO 41) In adult patients with active PsA despite treatment with anti-IL-12/23 monotherapy: Conditionally recommend switching to TNFi over anti-IL-17 (PICO 38), or over adding MTX to anti-IL-12/23 (PICO 36) In patients with active PsA with psoriatic spondylitis/axial disease despite treatment with NSAIDs: Conditionally recommend switching to TNFi over anti-IL-17 (PICO 46), or anti-IL-12/23 (PICO 45) In adult patients with active PsA and predominant enthesitis who are both oral small molecule*- and biologic treatment-naïve: Conditionally recommend starting TNFi over an oral small molecule (specifically apremilast) (PICO 48A) In adult patients with active PsA and predominant enthesitis despite treatment with an oral small molecule*: Conditionally recommend switching to TNFi over anti-IL-17 (PICO 53), anti-IL-12/23 (PICO 52), or another oral small molecule (PICO 49) In adult patients with active PsA and concomitant active IBD who have not received an oral small molecule* or biologic treatment: Conditionally recommend starting monoclonal antibody TNFi over an oral small molecule (PICO 62) In adult patients with active PsA and concomitant active IBD despite treatment with an oral small molecule*: Strong recommendation for switching to a monoclonal antibody TNFi over biologic TNF-soluble receptors (i.e. etanercept) (PICO 58) or anti-IL-17 (PICO 59) Conditionally recommend switching to TNFi monoclonal antibody over anti-IL-12/23 (PICO 61)	EU: [21] US: [22]
PsO, plaque PsO	In patients with moderate-to-severe PsO with an inadequate response, contraindication, or intolerance to 1 L conventional therapy, consider TNFi (e.g. infliximab), anti-IL-12/23, or PDE-4 small molecule inhibitors	Infliximab monotherapy is recommended in adult patients with: Moderate-to-severe plaque PsO (SoR: A) Plaque PsO of any severity when associated with significant PsA (infliximab also inhibits radiographically detected damage of joints in patients with PsA) (SoR: A) Moderate-to-severe plaque PsO affecting the palms and soles (plaque-type palmoplantar PsO), nails, or scalp (all SoR: B) Other subtypes (pustular or erythrodermic) of moderate-to-severe plaque PsO (SoR: C) In adult patients with moderate-to-severe plaque PsO, infliximab may be combined with the following: MTX (SoR: B), topicals (e.g. high-potency CS with or without a vitamin D analog) (SoR: B), acitretin (SoR: C), or apremilast (when clinically indicated; SoR: C)	EU: [23] US: [24]

*MTX, sulfasalazine, leflunomide, cyclosporine, or apremilast.

1 L: first-line; 2 L: second-line; AS: ankylosing spondylitis; bDMARD: biologic disease-modifying antirheumatic drug; CD: Crohn’s disease; CoE: certainty of evidence; CS: corticosteroid; DMARD: disease-modifying antirheumatic drug; ECCO: European Crohn’s and Colitis Organisation; ESPGHAN: European Society for Paediatric Gastroenterology, Hepatology and Nutrition; IBD: inflammatory bowel disease; IL: interleukin; IV: intravenous; JAK: Janus kinase; MTX: methotrexate; NASPGHAN: North American Society for Pediatric Gastroenterology, Hepatology and Nutrition; NSAID: nonsteroidal anti-inflammatory drug; PDE-4: phosphodiesterase-4; PICO: Patient-Intervention-Comparator-Outcome; PsA: psoriatic arthritis; PsO: psoriasis; RA: rheumatoid arthritis; SoR: strength of recommendation; TNF: tumor necrosis factor; TNFi: tumor necrosis factor inhibitor; tsDMARD: targeted synthetic disease-modifying antirheumatic drug; UC: ulcerative colitis

Table 2. Approved indications for infliximab medicines, including biosimilars, in Europe and the USA.

Disease	EU indication [1,27]	US indication [2,28]
RA	In combination with MTX to reduce signs and symptoms and improve physical function in adults with active disease who have had an inadequate response to DMARDs (including MTX), or with severe, active, and progressive disease not previously treated with MTX or other DMARDs	In combination with MTX to reduce signs and symptoms, inhibit the progression of structural damage, and improve physical function in patients with moderate-to-severe active disease
CD	Moderate-to-severe active disease: adults who have failed to respond despite full and appropriate therapy with a CS and/or an immunosuppressive agent, or who are intolerant to, or have a contraindication to, such therapies Fistulizing, active disease: adults who have not responded despite a full and adequate course of therapy with first-line therapy (including antibiotics, drainage, and immunosuppressive therapy)	Reduce signs and symptoms, and induce and maintain clinical remission in adult patients with moderate-to-severe active disease who have had an inadequate response to conventional therapy Reduce the number of draining enterocutaneous and rectovaginal fistulas and maintain fistula closure in adult patients with fistulizing disease
Pediatric CD	Children and adolescents aged 6–17 years with severe, active disease for whom conventional therapy has failed (including a CS, an immunomodulator, and primary nutritional therapy), or who are intolerant to, or have medical contraindications for, such therapies	Reduce signs and symptoms, and induce and maintain clinical remission in patients with moderate-to-severe active disease who have had an inadequate response to conventional therapy
UC	Adults with moderate-to-severe active disease who have had an inadequate response to conventional therapy (including CS, mercaptopurine, or azathioprine), or who are intolerant to, or contraindicated for, such therapies	Reduce signs and symptoms, induce and maintain clinical remission and mucosal healing, and eliminate CS use in adults with moderate-to-severe active disease who have had an inadequate response to conventional therapy
Pediatric UC	Children and adolescents aged 6–17 years with severe active disease who have responded inadequately to conventional therapy (including CS, mercaptopurine, or azathioprine), or who are intolerant to, or contraindicated for, such therapies	Reduce signs and symptoms, and induce and maintain clinical remission in patients with moderate-to-severe active disease who have had an inadequate response to conventional therapy
AS	Adults with severe, active disease who have had an inadequate response to conventional therapy	Reduce signs and symptoms in patients with active disease
PsA	In combination with MTX in adults with active and progressive disease with an inadequate response to previous DMARD therapy, or as monotherapy in patients who are intolerant to, or contraindicated for, MTX	Reduce signs and symptoms of active arthritis, inhibit the progression of structural damage, and improve physical function
PsO (EU), plaque PsO (USA)	Adults with moderate-to-severe plaque PsO who are intolerant to, or have a contraindication for, other systemic therapy (including ciclosporin, MTX, or PUVA), or for whom those therapies have failed	In combination with MTX to reduce signs and symptoms, inhibit the progression of structural damage, and improve physical function in patients with moderate-to-severe active disease

AS: ankylosing spondylitis; CD: Crohn’s disease; CS: corticosteroid; DMARD: disease-modifying antirheumatic drug; MTX: methotrexate; PsA: psoriatic arthritis; PsO: psoriasis; PUVA: psoralen plus ultraviolet; RA: rheumatoid arthritis; UC: ulcerative colitis.

Figure 1. Timeline highlighting key studies for GP1111. ACR20: American College of Rheumatology 20% improvement criteria; AxSpA: axial spondyloarthritis; CD: Crohn’s disease; EMA: European Medicines Agency; FDA: US Food and Drug Administration; HBI: Harvey–Bradshaw Index; IV: intravenous; OLE: open-label extension; PsA: psoriatic arthritis; PMS: Partial Mayo Score; RA: rheumatoid arthritis; ref-IFX: reference infliximab; UC, ulcerative colitis.

Figure 2. Timeline highlighting key studies for GP1111. Adapted from Cohen SB, et al. Arthritis Res Ther. 2018;20:155 [37]. Image adapted under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.Org/licenses/by/4.0/).

^aIntravenous infliximab 3 mg/kg was given as an induction regimen at Weeks 0, 2, and 6, followed by maintenance treatment with a 3 mg/kg dose starting at Week 14 and continuing every 8 weeks thereafter. Dose escalation to 5 mg/kg infliximab was permitted at or after Week 14 for patients with inadequate response. EOT, end of treatment.

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