Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Adalimumab

Klassificering: A

Preparat: AMGEVITA, Hulio, Humira, Humira®, Hyrimoz, Idacio, Imraldi

ATC kod: L04AB04

Substanser: adalimumab

Sammanfattning

Adalimumab 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.

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

In a randomized, double-blind, dose-titration study involving patients (13 men, 47 women) with rheumatoid arthritis receiving either adalimumab (0.25, 0.5, 1, 3, or 5 mg/kg) or placebo, clearance across all doses of adalimumab was 30% higher in women. However, the difference appeared to be mainly due to differences in body weight (23%) between men and women. The number of men receiving adalimumab was small (10 men, 35 women) [1]. The original manufacturer report that no sex-related pharmacokinetic differences have been observed after correction for a patient’s body weight [2]. Pharmacokinetics shows no differences between men and women when corrected for bodyweight. However, in adults adalimumab is administrated as a fixed dose. No studies with a clinically relevant sex analysis regarding the dosing of adalimumab have been found.

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]. Also, an open-label study involving patients with active RA treated with adalimumab 40 mg s.c. every other week (1246 men, 5227 women), showed that men had longer duration of remission (hazard ratio 1.28) [4].A large observational study (593 men, 2032 women) evaluating the effectiveness of adalimumab 40 mg every other week in RA showed that men had a lower disease activity and higher self-reported functional capacity at 12 months of therapy [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]. In another, open-label uncontrolled study (221 men, 221 women), patients received adalimumab 40 mg every other week in addition to standard therapy for 12 weeks. Men had higher response rates (odds ratio 2.24) [10].

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) [11].

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%) [12].

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) [13]. 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) [14].

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 [15]. 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) [16].

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 [17, 18].

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 [19]. Another systematic review of adherence, showed that female sex was a predictor of low adherence to TNFα- inhibitor therapy in inflammatory bowel disease [20]. 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) [21].

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) [22].

Försäljning på recept

Fler kvinnor än män hämtade ut injektionsvätska innehållande adalimumab (ATC-kod L04AB04) på recept i Sverige år 2015, totalt 5 294 kvinnor och 4 867 män. Det motsvarar 1,1 respektive 1,0 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 50-64 år hos kvinnor och i åldersgruppen 40-54 år hos män. Totalt sett var injektionsvätska innehållande adalimumab 1,1 gånger vanligare hos kvinnor [23].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2015-06-15

Referenser

  1. Weisman MH, Moreland LW, Furst DE, Weinblatt ME, Keystone EC, Paulus HE et al. Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate: a pilot study. Clin Ther. 2003;25:1700-21. PubMed
  2. Humira (adalimumab). DailyMed [www]. US National Library of Medicine. [updated 2014-12-01, cited 2015-06-15]. länk
  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. Burmester GR, Ferraccioli G, Flipo RM, Monteagudo-Sáez I, Unnebrink K, Kary S et al. Clinical remission and/or minimal disease activity in patients receiving adalimumab treatment in a multinational, open-label, twelve-week study. Arthritis Rheum. 2008;59:32-41. PubMed
  5. Kleinert S, Tony HP, Krause A, Feuchtenberger M, Wassenberg S, Richter C et al. Impact of patient and disease characteristics on therapeutic success during adalimumab treatment of patients with rheumatoid arthritis: data from a German noninterventional observational study. Rheumatol Int. 2012;32:2759-67. 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. Van den Bosch F, Manger B, Goupille P, McHugh N, Rødevand E, Holck P et al. Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions. Ann Rheum Dis. 2010;69:394-9. PubMed
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
  21. 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
  22. 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
  23. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Författare: Linnéa Karlsson Lind, Desirée Loikas

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson