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Infliximab

Klassificering: A

Preparat: Flixabi, Inflectra, Remicade, Remsima, ZESSLY

ATC kod: L04AB02

Substanser: infliximab

Sammanfattning

Infliximab används vid flera autoimmuna tillstånd. Flera studier har visat att män som behandlas med TNFα-hämmare vid reumatoid artrit är mer benägna att uppnå remission än kvinnor. Även vid Crohns sjukdom har män visat sig svara bättre på behandling med infliximab än kvinnor.

Två stora svenska registerstudier har visat att kvinnor med reumatoid artrit initierades på behandling med TNFα-hämmare på en högre nivå av självupplevd sjukdomsaktivitet än för män, men på samma nivå av läkarrapporterad sjukdomsaktivitet.

En studie har visat att allergiska reaktioner av infliximab var vanligare hos kvinnor. Studier har visat att incidensen av hudbiverkningar av TNFα-hämmare var vanligare hos kvinnor.
 
Vår bedömning är att de beskrivna skillnaderna inte motiverar olika dosering eller behandling hos kvinnor och män.

Additional information

Pharmacokinetics and dosing

Infliximab pharmacokinetics has been analyzed in patients with inflammatory bowel disease. Patients received 5 mg/kg infusions at weeks 0, 2, 4 and 8 followed by every 8 weeks. The study showed that volume of distribution was higher in men than in women [1]. However, another study found no sex differences in infliximab volume of distribution or clearance [2].

Infliximab is dosed per kilogram bodyweight.

Effects

Rheumatoid arthritis

Several studies have shown that men have a greater chance to achieve remission in rheumatoid arthritis (RA). A large observational study involving RA patients (165 men, 840 women) found a relative risk of 1.51 for remission in men within the first 14.5 months of therapy with standard doses of TNFα-inhibitors (infliximab, etanercept or adalimumab) [3].

Another register study (824 men, 2487 women) also showed that women with RA were less likely to achieve remission than men at 6 months following therapy with infliximab (odds ratio 0.60) or etanercept (odds ratio 0.61) [4]. A clinical trial in Japanese patients (39 men, 312 women) showed that male sex was related to response of infliximab given in standard doses to patients with RA [5].

A Swedish observational study (252 men, 446 women) showed that fewer women with RA receiving anti-rheumatic agents (mainly sulfasalazine or methotrexate) were in remission at follow-up at 2 and 5 years than men. Disease activity, assessed by the doctor, had decreased less in women than in men. However, women had a higher baseline disease activity [6]. Contrary to these findings, a large observational study of patients with established RA (353 men, 1212 women) showed that sex did not predict the response to TNFα-inhibitors (infliximab, etanercept or adalimumab) [7].

Psoriatic arthritis

Poorer treatment response among women treated with TNFα inhibitors have also been described in patients with psoriatic arthritis. In a British observational controlled study (280 men, 316 women), multivariate analysis showed that women treated with TNFα-inhibitors had lower response and remission rates at 6 months (odds ratio 0.51 and 0.34, respectively) than men [8]. A Danish register study showed that women had shorter treatment duration and men had better clinical response (odds ratio 1.5) [9].

Crohn disease

The efficacy of long-term infliximab therapy in patients with Crohn disease has been examined in an observational cohort study (86 men, 124 women). Multivariate analysis showed that men had a lower likelihood of failure to respond to infliximab induction therapy (hazard ratio 0.34) and a lower likelihood of failure to achieve sustained clinical benefit of infliximab therapy (hazard ratio 0.49) [10]. The better response to TNFα-inhibitors in males is also described in children with Crohn disease. The efficacy of infliximab in children has been examined retrospectively from hospital records (123 boys, 71 girls). Infliximab was prescribed as monotherapy or in combination with immunomodulators (thiopurines or methotrexate). Boys were more likely than girls to have a complete response (odds ratio 2.24; 95%CI 1.09-4.60). However, male sex was the only factor associated with secondary loss of response, defined as complete loss of benefit from infliximab, despite adjustment of dose and/or dosing interval. The sex differences persisted when controlling for induction response and Tanner stage (state of puberty). This benefit could not be explained by differences in weight-adjusted or BMI-adjusted infliximab dose [11].

Ankylosing spondylitis

Response to TNFα-inhibitors (infliximab, etanercept or adalimumab) in patients with ankylosing spondylitis has been evaluated in an observational study (152 men, 68 women). Men were more likely to have a better treatment response at 6 months of treatment (odds ratio 2.99) [12].

Adverse effects

Sex differences in adverse drug reactions to immune suppressive medication have been analyzed in a review of medical records (386 men, 457 women). For patients treated with infliximab, more women than men suffered from adverse drug reaction (odds ratio 2.2, 95%CI 1.2-4.1). For patients treated with adalimumab, there were no significant differences between men and women in experience of adverse drug reactions. The most frequent adverse drug reaction to infliximab and adalimumab was allergic reactions, with a higher rate in women than men. No other sex-specific adverse drug reactions to TNFα-inhibitors were observed.  As a result of adverse drug reactions, a higher proportion of women than men treated with TNFα-inhibitor stopped the treatment (19% vs. 9%). Also, a higher proportion of women than men switched to another TNFα-inhibitor (15% vs. 6%) [13].

The incidence of cutaneous adverse events in patients with chronic inflammatory arthritis who receive TNFα-inhibitors (infliximab, etanercept or adalimumab) has been evaluated in a prospective study (92 men, 165 women). After 60 months of follow-up, 27.6% had experienced some type of adverse event involving the skin. Of those, 81.7% were women.  Female sex was the main risk factor associated with cutaneous adverse events (odds ratio 2.84, 95%CI 1.90-5.63) [14]. An observational register study (2123 men, 3311 women) found an incidence rate ratio of cutaneous adverse events of 1.49 in women treated with TNFα-inhibitors (infliximab, etanercept or adalimumab) [15].

Reactions from infliximab infusion in children with Crohn disease or Ulcerative colitis has been retrospectively analyzed (55 boys, 56 girls). The incidence of reactions was 14% in girls and 2% in boys (p=0.03) [16].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

Disease characteristics at initiation of TNFα-inhibitor treatment (infliximab, etanercept or adalimumab) in men and women with rheumatoid arthritis have been analyzed in a Swedish register study (2204 men, 7098 women). The register includes data assessed both by patients and the physician. Women with rheumatoid arthritis were initiated on TNFα-inhibitor therapy at a higher level of disease when measured by patient, but at the same level as men when measured by physician [17]. Same results were shown in another similar register study (402 men, 1510 women). This may indicate that physicians were not taking the patient’s experiences into account in their decision of treatment. However, there were no differences between men and women in the choice of biologic agent (etanercept, adalimumab, infliximab, rituximab, abatacept, golimumab, certolizumab pegol, anakinra, tocilizumab, or ustekinumab) [18].

Several studies have shown that the delay to initiation of therapy for patients with rheumatoid arthritis is similar for men and women and that no differences in the proportion of men and women receiving biologic agents have been found [19, 20].

A systematic review of adherence to TNFα-inhibitors (infliximab, etanercept or adalimumab) in Crohn disease and rheumatoid arthritis showed that the most consistent factor associated with lower adherence was female sex [21]. Another systematic review of adherence, showed that female sex was a predictor of low adherence to TNFα- inhibitor therapy in inflammatory bowel disease [22]. In patients with rheumatoid arthritis, a study showed that women were more likely to discontinue infliximab therapy (hazard ratio 1.24) [23]. In contrast to his, male sex has been shown to be a predictor of discontinuation of TNFα-inhibitor treatment in Korean patients with ankylosing spondylitis (hazard ratio 0.327) [24].

A study has evaluated the effect of anti-drug antibodies on the clinical efficacy and withdrawal rate of TNFα-inhibitors (infliximab, etanercept, or adalimumab) in patients with rheumatic diseases (21 men, 37 women). The only factor associated with development of anti-drug antibodies was female sex (odds ratio 8.3) [25].

Försäljning på recept

Läkemedel innehållande infliximab (ATC-kod L04AB02) används huvudsakligen på sjukhus och därför saknas könsspecifika användningsdata [26].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2015-06-08

Referenser

  1. Ternant D, Aubourg A, Magdelaine-Beuzelin C, Degenne D, Watier H, Picon L et al. Infliximab pharmacokinetics in inflammatory bowel disease patients. Ther Drug Monit. 2008;30:523-9. PubMed
  2. Fasanmade AA, Adedokun OJ, Ford J, Hernandez D, Johanns J, Hu C et al. Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis. Eur J Clin Pharmacol. 2009;65:1211-28. PubMed
  3. Atzeni F, Antivalle M, Pallavicini FB, Caporali R, Bazzani C, Gorla R et al. Predicting response to anti-TNF treatment in rheumatoid arthritis patients. Autoimmun Rev. 2009;8:431-7. PubMed
  4. Hyrich KL, Watson KD, Silman AJ, Symmons DP, British Society for Rheumatology Biologics Register. Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2006;45:1558-65. PubMed
  5. Yamanaka H, Tanaka Y, Sekiguchi N, Inoue E, Saito K, Kameda H et al. Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan (RECONFIRM). Mod Rheumatol. 2007;17:28-32. PubMed
  6. Forslind K, Hafström I, Ahlmén M, Svensson B, BARFOT Study Group. Sex: a major predictor of remission in early rheumatoid arthritis?. Ann Rheum Dis. 2007;66:46-52. PubMed
  7. Kristensen LE, Kapetanovic MC, Gülfe A, Söderlin M, Saxne T, Geborek P. Predictors of response to anti-TNF therapy according to ACR and EULAR criteria in patients with established RA: results from the South Swedish Arthritis Treatment Group Register. Rheumatology (Oxford). 2008;47:495-9. PubMed
  8. Saad AA, Ashcroft DM, Watson KD, Symmons DP, Noyce PR, Hyrich KL et al. Efficacy and safety of anti-TNF therapies in psoriatic arthritis: an observational study from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2010;49:697-705. PubMed
  9. Glintborg B, Østergaard M, Dreyer L, Krogh NS, Tarp U, Hansen MS et al. Treatment response, drug survival, and predictors thereof in 764 patients with psoriatic arthritis treated with anti-tumor necrosis factor α therapy: results from the nationwide Danish DANBIO registry. Arthritis Rheum. 2011;63:382-90. PubMed
  10. Sprakes MB, Ford AC, Warren L, Greer D, Hamlin J. Efficacy, tolerability, and predictors of response to infliximab therapy for Crohn's disease: a large single centre experience. J Crohns Colitis. 2012;6:143-53. PubMed
  11. Church PC, Guan J, Walters TD, Frost K, Assa A, Muise AM et al. Infliximab maintains durable response and facilitates catch-up growth in luminal pediatric Crohn's disease. Inflamm Bowel Dis. 2014;20:1177-86. PubMed
  12. Arends S, Brouwer E, van der Veer E, Groen H, Leijsma MK, Houtman PM et al. Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study. Arthritis Res Ther. 2011;13:R94. PubMed
  13. Zelinkova Z, Bultman E, Vogelaar L, Bouziane C, Kuipers EJ, van der Woude CJ. Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease. World J Gastroenterol. 2012;18:6967-73. PubMed
  14. Machado NP, Reis Neto ET, Soares MR, Freitas DS, Porro A, Ciconelli RM et al. The skin tissue is adversely affected by TNF-alpha blockers in patients with chronic inflammatory arthritis: a 5-year prospective analysis. Clinics (Sao Paulo). 2013;68:1189-96. PubMed
  15. Hernández MV, Sanmartí R, Cañete JD, Descalzo MA, Alsina M, Carmona L et al. Cutaneous adverse events during treatment of chronic inflammatory rheumatic conditions with tumor necrosis factor antagonists: study using the Spanish registry of adverse events of biological therapies in rheumatic diseases. Arthritis Care Res (Hoboken). 2013;65:2024-31. PubMed
  16. Friesen CA, Calabro C, Christenson K, Carpenter E, Welchert E, Daniel JF et al. Safety of infliximab treatment in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2004;39:265-9. PubMed
  17. Arkema EV, Neovius M, Joelsson JK, Simard JF, van Vollenhoven RF. Is there a sex bias in prescribing anti-tumour necrosis factor medications to patients with rheumatoid arthritis? A nation-wide cross-sectional study. Ann Rheum Dis. 2012;71:1203-6. PubMed
  18. Lesuis N, Befrits R, Nyberg F, van Vollenhoven RF. Gender and the treatment of immune-mediated chronic inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease and psoriasis: an observational study. BMC Med. 2012;10:82. PubMed
  19. Sokka T, Toloza S, Cutolo M, Kautiainen H, Makinen H, Gogus F et al. Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study. Arthritis Res Ther. 2009;11:R7. PubMed
  20. DeWitt EM, Lin L, Glick HA, Anstrom KJ, Schulman KA, Reed SD. Pattern and predictors of the initiation of biologic agents for the treatment of rheumatoid arthritis in the United States: an analysis using a large observational data bank. Clin Ther. 2009;31:1871-80; discussion 1858. PubMed
  21. Fidder HH, Singendonk MM, van der Have M, Oldenburg B, van Oijen MG. Low rates of adherence for tumor necrosis factor-α inhibitors in Crohn's disease and rheumatoid arthritis: results of a systematic review. World J Gastroenterol. 2013;19:4344-50. PubMed
  22. Lopez A, Billioud V, Peyrin-Biroulet C, Peyrin-Biroulet L. Adherence to anti-TNF therapy in inflammatory bowel diseases: a systematic review. Inflamm Bowel Dis. 2013;19:1528-33. PubMed
  23. Markenson JA, Gibofsky A, Palmer WR, Keystone EC, Schiff MH, Feng J et al. Persistence with anti-tumor necrosis factor therapies in patients with rheumatoid arthritis: observations from the RADIUS registry. J Rheumatol. 2011;38:1273-81. PubMed
  24. Kang JH, Park DJ, Lee JW, Lee KE, Wen L, Kim TJ et al. Drug survival rates of tumor necrosis factor inhibitors in patients with rheumatoid arthritis and ankylosing spondylitis. J Korean Med Sci. 2014;29:1205-11. PubMed
  25. Mok CC, van der Kleij D, Wolbink GJ. Drug levels, anti-drug antibodies, and clinical efficacy of the anti-TNFα biologics in rheumatic diseases. Clin Rheumatol. 2013;32:1429-35. PubMed
  26. Conicse. Stockholm: eHälsomyndigheten. 2015 [cited 2016-03-23.] länk

Författare: Linnéa Karlsson Lind, Desirée Loikas

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson