Open Access

Aspects concerning patient adherence to anti‑TNFα therapy in psoriasis: A decade of clinical experience

  • Authors:
    • Madalina Mocanu
    • Mihaela‑Paula Toader
    • Elena Rezus
    • Tatiana Taranu
  • View Affiliations

  • Published online on: September 16, 2019     https://doi.org/10.3892/etm.2019.8008
  • Pages: 4987-4992
  • Copyright: © Mocanu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Non‑adherence to psoriasis treatment has an important impact in controlling chronic disease evolution and the occurrence of systemic comorbidities. Biologic therapy represents a revolutionary treatment, many of the undesirable psychological and socio‑economical consequences of conventional topical or systemic therapies being avoided. Nevertheless, the discontinuation of biological therapy may occur due to facts related to the patient, to the lack of good communication between the patient and the physician or to the adverse or paradoxical reactions. We studied the non‑adherence reasons to anti‑TNFα agents (Infliximab, Adalimumab, Etanercept) used for treating 84 cases with moderate‑severe psoriasis. The results of our study over the past 10 years showed a 76.2% adherence rate, lowest in patients treated with Etanercept (70.9%). Relative to the anti‑TNF agent used, the highest adherence rate was recorded in Adalimumab (80.8%), followed by Infliximab (76.5%) and Etanercept (70.9%). We have noticed differences between the rates of adhesion to therapy with different anti‑TNFα agents, but with no statistical significance. The main adverse effects that occurred during anti‑TNFα therapy were: local reaction to the drug, mild infectious events, allergic reactions, cardiotoxicity, alopecia areata, pancreatitis, eosinophilia, thrombocytopenia. Anti‑TNF therapy was discontinued in one case of endocarditis, one case with tuberculous laryngitis and another one with polydiscitis (Adalimumab), a case of colon cancer and one of pregnancy (Etanercept) and one paradoxical reaction (Infliximab).

Introduction

Psoriasis is an inflammatory condition with chronic evolution, multifactorial etiology and complex pathogenesis, involving genetic, immunological and environmental factors. Skin lesions, erythematous-squamous plaques with inconstant osteo-articular and nail involvement may be associated with systemic damage, such as cardiovascular diseases, metabolic syndrome or autoimmune disorders (1,2). Psoriasis is a disease with a severe psychosocial impact, comparable to diabetes and cancer (3,4).

The treatment is adapted to the extent of the lesions, the duration of the disease evolution, the comorbidities and the general biological status of the patient. In mild or moderate clinical forms of psoriasis, with lesions not exceeding 10% of the skin surface, local therapy is recommended. In severe forms of psoriasis, with extensive lesions or resistant to either topical therapy or UVA/NB-UVB therapy, a systemic treatment with antiproliferative medicines (methotrexate, retinoids) or immunomodulators, such as cyclosporine or fumaric acid is established (5,6). Lack of response constitutes an eligibility criterion for biological therapy (7).

Biological agents are a class of revolutionary pharmaceuticals useful in many immunological-mediated diseases. Those intended for psoriasis include selective inhibiting biological agents of anti-TNFα tumor necrosis factor, of interleukin 12/23 or interleukin 17A (8,9). The longest experience has been gained by anti-TNFα agents (infliximab, etanercept, adalimumab).

Despite the modern therapeutic options being destined to patients with psoriasis, obtaining satisfactory clinical and biological results requires optimal patient compliance with the treatment. The term ‘compliance’ has been criticized for having an authoritative message and referring in particular to the rigor with which a patient is following the prescribed treatment, not to the doctor's additional recommendations on appropriate diet or change of lifestyle (10). For these reasons, the term adhesion or even therapeutic alliance is currently preferred to suggest an approach that indicates a high degree of involvement of both the patient and the physician in the therapeutic act (11). As an extended definition, adherence is expressed in patients who have been treated for a certain period of time and who have followed both the indications and the doctor's prescription following treatment without interruption. According to the World Health Organization (WHO), adherence is ‘the extent to which the behavior of a person taking medication, following a diet, making lifestyle changes corresponds to the recommendations accepted by the physician’ (12).

Biological agents, targeted, rational and long-term individualized therapy are able to increase adherence to treatment for patients with psoriasis, due to the ease of drug administration, the costs incurred by the national health insurance system, the clinical effectiveness shortly after treatment initiation, the long-term safety profile. Non-adherence to biological therapy is found, however, correlated with a number of factors that involve both the patient and the attending physician (13,14).

This study aimed to identify the main factors involved in the non-adherence of patients with psoriasis to anti-TNFα biological therapy, as well as to analyze the optimal methods of combating this phenomenon with negative echoes in terms of disease evolution over time.

Patients and methods

The current retrospective, observational study includes patients with moderate-severe psoriasis vulgaris treated with biological anti-TNFα agents. The study group encompassed 84 patients who underwent therapy with anti-TNFα biological agents in the Department of Dermatology at CF University Hospital Iasi (Iasi, Romania) between January 2009 and October 2018. The Ethics Committee of the Railways University Hospital Iasi (Iasi, Romania) approved the current study. The patients were aged 9–82 years, 48 women and 35 men, 66 from urban areas and 18 from rural areas.

Depending on the biological agent administered, the patients were divided into 3 groups: group 1 included 34 patients who received Infliximab (5 mg/kg iv every 8 weeks), group 2 consisted of 26 patients treated with Adalimumab (40 mg subcutaneously every 2 weeks) and group 3 had 24 patients treated with Etanercept (50 mg subcutaneously every week). The patients' eligibility was based on the inclusion and exclusion criteria regarding the general protocol for biological therapy. The analysis of the clinical and paraclinical parameters during the biological therapy allowed the evaluation of the adherence to treatment, as well as the investigation of the factors responsible for non-adherence.

Statistical analysis

Descriptive and analytical methods were used in the statistical analysis. Once the data were collected, in an accessible form to ensure their informational character, the processing was performed. The confidence intervals, at the significance threshold of 95%, were used in the data presentation, and the χ2 and Student's t-tests were used to assess the differences. The data were centralized in EXCEL and SPSS 13.0 databases and processed with the statistical functions they are suitable for. In calculating the significant difference between two environments, the Student's t-test takes into account the variability measurement and the weight of the observations. The accepted significance threshold was 95%. χ2 test is a nonparametric test comparing two or more frequencies distributed from the same population; it applies when the expected events are excluded.

Results

From an epidemiological point of view, the study group consisted predominantly of male patients (57.1%) with a M/F ratio of 1.4/1 (Fig. 1). Most subjects were from the urban area, the U/R ratio being 3.7/1 (Fig. 2). The distribution by areas of origin and sex did not show significant differences: 75% of women and 83.3% of men came from the urban environment (P=0.514), statistically revealing the homogeneity of the study group.

Distribution by age group reveals the high proportion of cases in the 60–69 age group, both in women and men. Since the mean age of the group was 58.88 years and the highest weight of cases is found in patients >60 years (54.8%), we chose this age as reference in the statistical processing (Fig. 3).

Infliximab was used in 40.5% of the cases, the majority in men (72.7 vs. 27.3%, P=0.038) and Adalimumab was recommended in 30.9% of the patients, frequently women (60 vs. 40%, P=0.038) (Fig. 4).

Discontinuation of therapy was observed in 20 of the 84 patients enrolled in the study (22.6%) for reasons related either to therapy (adverse events) or to the patient. The highest rate of treatment discontinuation was observed in the Etanercept group (29.1), followed by the Infliximab group (23.5%) and Adalimumab group (19.2%) (Fig. 5).

In most cases, the reasons for discontinuing biological therapy were represented by adverse events. In the Infliximab group these were: allergic reactions (angioedema and deep urticaria) in three cases (8.82% of all patients treated with Infliximab) representing 3.57% of the total number of patients enrolled in the study, NYHA class III heart failure one patient (2.94% of all patients in the Infliximab group), viral hepatitis with C virus in one patient (2.94% of all patients treated with Infliximab). One patient developed paradoxical psoriasis and cataract (2.94% of all patients treated with Infliximab). Home relocation was the reason for discontinuing the therapy in one patient (2.94% of all patients in the Infliximab group). Patients who discontinued Infliximab accounted for 8.3% of the total number of patients.

In the Adalimumab group, the therapy was discontinued in the context of the following adverse events: polydiscitis in one case (3.84% of all patients in the Adalimumab group), infectious endocarditis in one case (3.84%), laryngeal tuberculosis, one case (3.84%), hypereosinophilic syndrome, one case (3.84%) and breast cancer, one case (3.84%), each adverse event representing 1.19% of the total. Patients who discontinued Adalimumab accounted for 5.95% of the total number of patients.

In the Etanercept group, adverse events that led to the interruption of therapy were: eosinophilic cellulitis in two cases (8.33% of all patients in the Etanercept group), accounting for 2.38% of the total number of patients, colon cancer occurred in one patient (4.16% of all patients in the Etanercept group), representing 1.19% of the total number of patients, alopecia areata in one case (4.16%), pancreatitis in one case (4.16%) and thrombocytopenia in one case (4.16%). Pregnancy occurred during biologic therapy in one patient (4.16% of all patients in the Etanercept group) and led to interruption of Etanercept. Patients who interrupted Etanercept accounted for 8.3% of the total number of patients (Table I).

Table I.

Distribution of events leading to discontinuation of therapy.

Table I.

Distribution of events leading to discontinuation of therapy.

Infliximab (n=8/34)Adalimumab (n=5/26)Etanercept (n=7/24)



Adverse effects% of Infliximab group% of all patients% of Adalimumab group% of all patients% of Etanercept group% of all patients
Angioedema urticarial8.823.57
Infectious endocarditis 3.841.19
Hypereosinophilic syndrome3.841.19
Paradoxical psoriasis2.941.19
Cataract2.941.19
Eosinophilic cellulite8.332.38
IC class III NYHA2.941.19
Hepatitis C virus2.941.19
Tuberculous laryngitis3.841.19
Thrombocytopenia4.161.19
Pancreatitis4.161.19
Breast cancer3.841.19
Colon cancer4.161.19
Polydiscitis3.841.19
Move home2.941.19
Pregnancy4.161.19
Alopecia4.161.19
Total adverse effects23.59.5219.25.9529.18.33

Overall adverse events that led to treatment discontinuation occurred in 52.6% of men and 47.4% of women (P=0.179). There were no significant differences in the reason for non-adherence to treatment based on the background (P=0.280). In conclusion, the study group had a predominantly male distribution (57.1%), from urban areas (68.6%) aged between 28 and 82 years. Statistically, the homogeneity of the group by sex, age groups, and background was demonstrated. Non-adherence to therapy was noted in 22.6% of the patients, most commonly in those treated with Etanercept (29.1%). The adherence rate for the entire patient population was of 76.2%, statistical analysis revealing a lack of direct correlation between the incidence of adverse events and biologic therapy (P=0.00213).

Discussion

Biological therapy in psoriasis is a modern treatment alternative with long-term proven efficacy and safety profile. Clinical experience with biological agents from the anti-TNFα class allows them to be categorized as superior to conventional systemic therapy for moderate-severe psoriasis. Rapid remission of symptomatology, its maintenance over treatment, easy administration, significant improvement in the quality of life are the arguments that reinforce this idea (15,16).

The adhesion of patients with psoriasis to anti-TNFα therapy is an essential condition for obtaining and maintaining the expected therapeutic outcome, but also a long-term indicator of patient satisfaction. The risk of reactivating the disease in the context of cessation of treatment confers a key role in maintaining the favorable clinical effects to the notion of adherence to therapy (17,18).

The rate of adherence to biological therapy is clearly superior compared to adherence to classical topical or systemic treatments, but the literature data on this topic varies, depending on the size of the group studied and the biological agent used (19).

Thus, a 2017 study conducted in Germany for 31 months in 13 dermatology centers showed a rate of adhesion to anti-TNFα therapy of ~85%. Other studies concluded that adherence rates ranged between 65 and 96.7% one year after initiation of anti-TNFα therapy with a 40–70% decrease in adherence after 4 years of therapy (20). Another large study on 747 patients concludes on a high adherence to Infliximab of 70% after 4 years of treatment as compared to Etanercept and Adalimumab with a 40% adherence rate (21).

The results of the current study, which included 84 patients treated with anti-TNFα (Infliximab, Adalimumab, Etanercept) over the past 10 years, showed an overall 76.2% adherence rate, lowest in patients treated with Etanercept (70.9%). Relative to the anti-TNF agent used, the highest adherence rate was recorded in Adalimumab (80.8%), followed by Infliximab (76.5%) and Etanercept (70.9%). We noted differences between the rates of adhesion to therapy with different anti-TNFα agents, but with no statistical significance (P=0.00213).

The main adverse events of anti-TNFα therapy reported in literature are cardiovascular diseases, increased risk of latent tuberculosis reactivation, increased risk of infections, malignancy, injection site reactions, haematological disorders (22,23). These events may be a factor of non-adherence to therapy. In our study, patients treated with Infliximab experienced: allergic reactions (8.8%), cardiotoxicity (NYHA class III congestive heart failure 2.9%), hepatitis C (2.9%), results which are comparable to those published in other studies (23,24).

The most common adverse events reported during treatment with Adalimumab are minor injection site reactions, occurring in 12–37% of the treated cases. In addition, Adalimumab increases the risk of infection or reactivation of chronic latent infections, such as viral hepatitis or TB (22). Only one case of tuberculous infection (tuberculous laryngitis (3.8%) and a bacterial endocarditis (3.8%) were recorded in our study during Adalimumab therapy.

Numerous research studies focused on the efficacy and safety profile of Etanercept. The main side effects to Etanercept reported in the literature are local reactions on injection site (eosinophilic cellulitis) and the risk of infection. In our study, 8.3% of the patients treated with Etanercept developed eosinophilic cellulitis. Other events recorded during Etanercept therapy were: malignancies (4.1% colon cancer), alopecia areata (4.1%), and pancreatitis (4.1%). Various studies have focused on the analysis of long-term safety of Etanercept administration and concluded on a similar rate of side effects after 96 and 144 weeks of monitoring. They have also concluded that the rate of major adverse events, such as severe infections and tumors, is higher than in the general population (24,25).

On the one hand, adherence to long-term treatment is influenced by its nature; on the other hand, it is influenced by the patient's compliance based on an optimal physician-patient relationship. Two cases of non-adherence due to factors independent of therapy (home relocation and pregnancy) were reported in our study. There were no matters involving refusal to follow the prescribed treatment, under or overdosing, intermittent dosing, premature discontinuation, addition or waiver of medicine without medical advice, non-compliance to the protocol regimen. Serious side events were rare and difficult to interpret widely on a small batch of patients.

Other non-adherence reasons reported in literature are loss of insurance, long-term remission of the skin lesions or lack of confidence in pharmaceutical drugs. Even though vitamins, minerals and herb supplements (zinc, selenium, B12, fish oil, curcumin, aloe vera extract) are sometimes prescribed in psoriasis due to their mainly antioxidant action, we consider it a complementary therapeutical instrument (26,27).

The case with PR and aggravated psoriasis under Infliximab therapy benefited from switch to anti-IL17 therapy. Potential causes for paradoxical psoriasis under TNFα are the imbalance of the key cytokines in the pathophysiological chain of the disease (TNFα, IFNα, IL12/23, IL17), the differences between the immunological properties of monoclonal antibodies and soluble TNFα receptor, as well as the change of the immunological profile from Th1 to Th2, with the consequent increase in antibody production (28,29).

Malignancy caused interruption of anti-TNF biologic therapy in two patients in the study (breast cancer: Adalimumab/colon cancer: Etanercept), but it is difficult to interpret the contribution of biologic therapy in the etiopathogenesis of these neoplasms (30)]. Prior to the biological treatment, no tumor markers were used to stratify the risk of patients treated with anti-TNF to develop a form of cancer. Studies do not indicate a clear correlation between anti-TNFα treatment and an increased risk of malignancy, which allows us to interpret the occurrence of these events independently of the biological therapy for psoriasis.

In conclusion, adherence is a complex process, which represents an important parameter in assessing the long-term effectiveness of biological therapy. Improved adhesion is based on the patient's transformation into an active co-participant to his/her own healing through an optimal communication with the treating physician, as well as on an easy way to carry out the treatment, on its safety and the application of pharmacovigilance principles.

Acknowledgements

Professional editing, linguistic and technical assistance performed by Individual Service Provider Irina Radu, certified translator in Medicine and Pharmacy.

Funding

No funding was received.

Availability of data and materials

The data that support the findings of this study are available from the archives of the Railways University Hospital Iasi, (Iasi, Romania), but restrictions apply to the availability of these data which are not publicly available. Data are, however, available from the authors upon reasonable request and with permission from the Railways University Hospital Iasi.

Author's contributions

MM, MPT, ER, TT contributed equally to acquisition, analysis and systematization of data, manuscript writing and critical revision of it for important intellectual content. All the authors read and approved the final version of the manuscript.

Ethics approval and consent to participate

The Ethics Committee of the Railways University Hospital Iasi (Iasi, Romania) approved the current study.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

Schadler ED, Ortel B and Mehlis SL: Biologics for the primary care physician: Review and treatment of psoriasis. Dis Mon. 65:51–90. 2019. View Article : Google Scholar : PubMed/NCBI

2 

Căruntu C, Boda D, Căruntu A, Rotaru M, Baderca F and Zurac S: In vivo imaging techniques for psoriatic lesions. Rom J Morphol Embryol. 55 (Suppl):1191–1196. 2014.PubMed/NCBI

3 

Batani A, Brănișteanu DE, Ilie MA, Boda D, Ianosi S, Ianosi G and Căruntu C: Assessment of dermal papillary and microvascular parameters in psoriasis vulgaris using in vivo reflectance confocal microscopy. Exp Ther Med. 15:1241–1246. 2018.PubMed/NCBI

4 

Negrei C, Ginghină O, Căruntu C, Burcea Dragomiroiu GTA, Jinescu G and Boda D: Investigation relevance of methotrexate polyglutamates in biological systems by high performance liquid chromatography. Rev Chim. 66:766–768. 2015.

5 

Negrei C, Arsene AL, Toderașcu CD, Boda D and Ilie M: Acitretin treatment in psoriasis may influence the cell membrane fluidity. Farmacia. 60:767–771. 2012.

6 

Negrei C, Căruntu C, Ginghina O, Dragomiroiu GTAB, Toderascu CD and Boda D: Qualitative and quantitative determination of methotrexate polyglutamates in erythrocytes by high performance liquid chromatography. Rev Chim. 66:607–610. 2015.

7 

Sbidian E, Chaimani A, Garcia-Doval I, Do G, Hua C, Mazaud C, Droitcourt C, Hughes C, Ingram JR, Naldi L, et al: Systemic pharmacological treatments for chronic plaque psoriasis: A network meta-analysis. Cochrane Database Syst Rev. 12:CD0115352017.PubMed/NCBI

8 

Olteanu R, Zota A and Constantin M: Biosimilars: An update on clinical trials (review of published and ongoing studies. Acta Dermatovenerol Croat. 25:57–66. 2017.PubMed/NCBI

9 

Olteanu R, Constantin MM, Zota A, Dorobantu DM, Constantin T, Serban ED, Balanescu P, Mihele D and Gheuca-Solovastru L: Original clinical experience and approach to treatment study with interleukine 12/23 inhibitor in moderate-to-severe psoriasis patients. Farmacia. 64:918–921. 2016.

10 

Zambrano R, Duitama JF, Posda JI and Flórez JF: Perception of adherence to treatment among patients with cardiovascular risk factors. Rev Fac Nac Salud Publica. 30:163–174. 2012.

11 

Tatu AL and Nwabudike LC: Metoprolol-associated onset of psoriatic arthropathy. Am J Ther. 24:e370–e371. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Sabate E: Adherence to Long-Term Therapies: Evidence for ActionWorld Health Organization; Geneva: 2003, simplehttps://www.who.int/chp/knowledge/publications/adherence_report/en/

13 

Boda D, Negrei C, Nicolescu F and Balalau C: Assessment of some oxidative stress parameters in methotrexate treated psoriasis patients. Farmacia. 62:704–710. 2014.

14 

Radtke MA and Augustin M: Economic considerations in psoriasis management. Clin Dermatol. 26:424–431. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Ross C, Marshman G, Grillo M and Stanford T: Biological therapies for psoriasis: Adherence and outcome analysis from a clinical perspective. Australas J Dermatol. 57:137–140. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Raval K, Lofland JH, Waters H and Piech CT: Disease and treatment burden of psoriasis: Examining the impact of biologics. J Drugs Dermatol. 10:189–196. 2011.PubMed/NCBI

17 

Schaarschmidt ML, Kromer C, Herr R, Schmieder A, Goerdt S and Peitsch WK: Treatment satisfaction of patients with psoriasis. Acta Derm Venereol. 95:572–578. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Zschocke I, Ortland C and Reich K: Evaluation of adherence predictors for the treatment of moderate to severe psoriasis with biologics: The importance of physician-patient interaction and communication. J Eur Acad Dermatol Venereol. 31:1014–1020. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Doshi JA, Takeshita J, Pinto L, Li P, Yu X, Rao P, Viswanathan HN and Gelfand JM: Biologic therapy adherence, discontinuation, switching, and restarting among patients with psoriasis in the US Medicare population. J Am Acad Dermatol. 74:1057–1065.e4. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Umezawa Y, Nobeyama Y, Hayashi M, Fukuchi O, Ito T, Saeki H and Nakagawa H: Drug survival rates in patients with psoriasis after treatment with biologics. J Dermatol. 40:1008–1013. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Gniadecki R, Kragballe K, Dam TN and Skov L: Comparison of drug survival rates for adalimumab, etanercept and infliximab in patients with psoriasis vulgaris. Br J Dermatol. 164:1091–1096. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Kim WB, Marinas JE, Qiang J, Shahbaz A, Greaves S and Yeung J: Adverse events resulting in withdrawal of biologic therapy for psoriasis in real-world clinical practice: A Canadian multicenter retrospective study. J Am Acad Dermatol. 73:237–241. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Kaushik SB and Lebwohl MG: Psoriasis: Which therapy for which patient: Focus on special populations and chronic infections. J Am Acad Dermatol. 80:43–53. 2019. View Article : Google Scholar : PubMed/NCBI

24 

Martín B, Sánchez-Carazo JL, Pérez-Ferriols A, Laguna C, Oliver V and Alegre V: Clinical experience with etanercept in the treatment of psoriasis. Actas Dermosifiliogr. 99:540–545. 2008.(In Spanish). View Article : Google Scholar : PubMed/NCBI

25 

Sehgal VN, Pandhi D and Khurana A: Biologics in dermatology: An integrated review. Indian J Dermatol. 59:425–441. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Niculet E, Neculia GV, Tatu AL and Buzia OD: Curcumin-extraction, physical and chemical analysis, formulas and control. Basic methods for further research. Mater Plast. 55:672–675. 2018.

27 

Nwabudike LC and Tatu AL: Using complementary and alternative medicine for the treatment of psoriasis: A step in the right direction. JAMA Dermatol. 155:6362019. View Article : Google Scholar : PubMed/NCBI

28 

Căruntu C, Boda D, Dumitrașcu G, Constantin C and Neagu M: Proteomics focusing on immune markers in psoriatic arthritis. Biomarkers Med. 9:513–528. 2015. View Article : Google Scholar

29 

Ilie MA, Căruntu C, Lixandru D, Tampa M, Georgescu SR, Constantin MM, Constantin C, Neagu M, Zurac SA and Boda D: In vivo confocal laser scanning microscopy imaging of skin inflammation: Clinical applications and research directions. Exp Ther Med. 17:1004–1011. 2019.PubMed/NCBI

30 

Căruntu C, Boda D, Musat S, Căruntu A and Mandache E: Stress-induced mast cell activation in glabrous and hairy skin. Mediators Inflamm. 2014:1059502014. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

December-2019
Volume 18 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Mocanu M, Toader MP, Rezus E and Taranu T: Aspects concerning patient adherence to anti‑TNFα therapy in psoriasis: A decade of clinical experience. Exp Ther Med 18: 4987-4992, 2019
APA
Mocanu, M., Toader, M., Rezus, E., & Taranu, T. (2019). Aspects concerning patient adherence to anti‑TNFα therapy in psoriasis: A decade of clinical experience. Experimental and Therapeutic Medicine, 18, 4987-4992. https://doi.org/10.3892/etm.2019.8008
MLA
Mocanu, M., Toader, M., Rezus, E., Taranu, T."Aspects concerning patient adherence to anti‑TNFα therapy in psoriasis: A decade of clinical experience". Experimental and Therapeutic Medicine 18.6 (2019): 4987-4992.
Chicago
Mocanu, M., Toader, M., Rezus, E., Taranu, T."Aspects concerning patient adherence to anti‑TNFα therapy in psoriasis: A decade of clinical experience". Experimental and Therapeutic Medicine 18, no. 6 (2019): 4987-4992. https://doi.org/10.3892/etm.2019.8008