- Email: [email protected]
Primary prevention of rheumatoid arthritis: A qualitative study in a high-risk population
Letters to the Editor / Joint Bone Spine 80 (2013) 667–676 b
Laboratoire Biomnis, 19, avenue Tony-Garnier, 69007 Lyon, France c Centre de radiologie diagnostique et interventionnelle, groupe IRIS, site du Confluent, 44277 Nantes, France d Service de médecine nucléaire, centre Catherine-de-Sienne, site du Confluent, 44277 Nantes, France
∗ Corresponding
author. Tel.: +33 6 31 05 99 81; fax: +33 2 28 25 51 59. E-mail address: [email protected] (O. Grossi) Accepted 28 February 2013 Available online 23 April 2013
doi:10.1016/j.jbspin.2013.02.015
Primary prevention of rheumatoid arthritis: A qualitative study in a high-risk population
a r t i c l e
i n f o
Keywords: Rheumatoid arthritis Primary prevention Qualitative study
First-degree relatives of patients with rheumatoid arthritis (RA) have a 4-fold to 5-fold increase in the risk of developing the disease [1]. Researchers are currently considering the development of strategies for preventing RA [2–5] and therefore for detecting high-risk individuals [6,7]. Here, our objectives were to determine:
673
• the expectations and level of interest of high-risk individuals regarding prophylactic interventions; • the desirable characteristics of prophylactic interventions, and; • the reasons that might lead individuals to participate in a randomized placebo-controlled trial. 1. Methods We used a qualitative approach to evaluate the opinions of candidates to primary RA prevention [8]. The study patients were individuals likely to be considered in the future for prophylactic treatment, i.e., first-degree relatives of RA patients. Face-to-face interviews lasting 30–45 minutes were conducted using a semi-structured interview guide. Additional details on the study methodology are available in the Appendix (Supplementary data). 2. Results We interviewed 20 first-degree relatives of RA patients (Appendix and Tables S1-S3, Supplementary data). Mean age was 45 years. Most of the participants (18/20) expressed interest in receiving prophylactic treatment should the results of screening tests indicate a high risk of developing RA. The cut-off above which participants said they would take prophylactic treatment was a 30% risk of developing RA within the next 5 years (Fig. 1). The participants usually expected that prophylactic therapy would consist in taking medications. However, a role for lifestyle changes and alternative medicines was also considered (Table 1). Although the main expectation was that the therapeutic intervention would prevent the development of RA (16/20), a treatment that would merely delay the development of RA was considered just as
Table 1 Main themes and subthemes identified by analysis of the interviews. Themes
Subthemes
Illustrative quotes
Representations of primary prevention interventions
Pharmacological intervention
Alternative medicines
“I think drugs would be involved, drugs that are less strong than those used to treat the disease.” (participant #2) “I envision preventive treatment involving nonmedical measures, for instance a special diet, participating in sports, or engaging in a specific lifestyle.” (participant #7) “I see this as natural medicines, such as devil’s claw.”
Expectations regarding primary prevention
To prevent the disease or delay its onset
“The preventive treatment should prevent the development of the disease. But if it only delays the disease, that’s better than nothing.” (participant #1)
Preferred route of administration
Oral route to avoid injections and to allow dosing at home
“Tablets are the simplest method.” (participant #4)
Lifestyle changes
Preference for a small number of doses
“Self-injection would not work for me.” (participant #19) “[. . .] If it’s an injection and I have to go somewhere to get it, since I work full time, that’s something I wouldn’t really like to do.” (participant #13) “It would have to be one dose every month or every week at the most. But not everyday.” (participant #10)
Possible barriers to accepting primary prevention
Adverse effects
“Finally, I would be willing to accept the risk of developing the disease, which is perhaps less burdensome than the drug.” “I prefer a drug that doesn’t affect the immune system [. . .] drugs can make us more vulnerable to infections.” (participant #15) “The problem is that getting sick at each dose is not compatible with working.” (participant #5)
Reasons for participating in a randomized trial
Feeling involved
“Well, I see so much suffering in my sister, so I think that if I can help with this study, then I’d be glad to.” (participant #9) “I would participate so that I would get the drug to prevent the disease from developing.” “I’d like to participate to help the researchers make progress.” (participant #10)
Expected personal benefit Altruism Barriers to participation in a randomized trial
Potential side effects Uncertainty about the true risk Placebo
“I’ve seen my sister and my brother. . ., there are diseases that develop because of drugs.” (participant #1) “For me, the problem is having to bother with taking drugs when we are healthy and not even sure we will get the disease.” (participant #18) “[. . .] I understand the role for the placebo in your studies, but to me it makes no sense.” (participant #13)
674
Letters to the Editor / Joint Bone Spine 80 (2013) 667–676 [7] Deane KD, Norris JM, Holers VM. Preclinical rheumatoid arthritis: identification, evaluation, and future directions for investigation. Rheum Dis Clin North Am 2010;36:213–41. [8] Hudelson P. La recherche qualitative en médecine de premier recours. Rev Med Suisse 2004;503:2497.
Fiona Novotny a Sylvie Haeny a Patricia Hudelson b Monica Escher c Axel Finckh d,e,∗ a Université de Genève, Geneva, Switzerland b Consultation Transculturelle et Interprétariat, Département de Médecine Communautaire, de premier recours et des urgences, Hôpitaux Universitaires de Genève, Geneva, Switzerland c Consultation douleur et soins palliatifs, Service de pharmacologie et toxicologie cliniques, Hôpitaux Universitaires de Genève, Geneva, Switzerland d Service de Rhumatologie, Hôpitaux Universitaires de Genève, 26, avenue Beau-Séjour, 1211 Geneva 14, Switzerland e Service d’Épidémiologie Clinique, Hôpitaux Universitaires de Genève, Geneva, Switzerland
Fig. 1. Theoretical risk of developing rheumatoid arthritis (RA) in the next 5 years above which high-risk individuals would be willing to take prophylactic treatment.
useful. The preferred route of administration was by mouth. A small number of doses was also considered crucial in the setting of primary prevention. Of the 20 participants, nine (40%) said they would choose parenteral treatment at widely spaced intervals and five (25%) daily oral treatment. Concern about serious adverse effects, most notably immune system impairment, was a limiting factor for many participants. Most of the interviewees report being willing to participate in a randomized placebo-controlled trial, evaluating the efficacy of primary prevention. Their motivations were a feeling of being involved, produced by having an affected relative, a desire to contribute to research, and hope for a possible personal benefit. In conclusion, the results of this study suggest that primary prevention of RA may meet the expectations of the target population, provided means are available for identifying individuals at high risk for developing the disease (≥30%). Minimal constraints and a good safety profile are crucial features of future prophylactic treatments. Participation in studies designed to develop prophylactic strategies for RA seems acceptable to the target population. Funding: This project received financial support from the Fonds National Suisse de la Recherche Scientifique [3200B0 120639/1–AF] and Fondation Rheumasearch.
∗ Corresponding
author. Service de Rhumatologie, Hôpitaux Universitaires de Genève, 26, avenue Beau-Séjour, 1211 Geneva 14, Switzerland. Fax: +41 22 382 3535. E-mail address: axel.fi[email protected] (A. Finckh) Accepted 27 March 2013 Available online 5 July 2013
doi:10.1016/j.jbspin.2013.05.005
Coexistence of seropositive rheumatoid arthritis and SAPHO syndrome
a r t i c l e Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
i n f o
Keywords: Rheumatoid arthritis SAPHO syndrome Anti-cyclic citrullinated protein antibodies (ACPA)
Appendix A. Supplementary data 1. Case report Supplementary data (appendix and Tables S1-S3) associated with this article can be found, in the online version, at http://www.sciencedirect.com and doi:10.1016/j.plantsci.2004. 08.011. References [1] Silman AJ, Hennessy E, Ollier B. Incidence of rheumatoid arthritis in a genetically predisposed population. Br J Rheumatol 1992;31:365–8. [2] Primary prevention of rheumatoid arthritis [Internet]. Current controlled trials. 2005 [cited 2007]. Available from: http://www.controlledtrials.com/mrct/trial/231203/Schaardenburg [3] Klareskog L, Gregersen PK, Huizinga TW. Prevention of autoimmune rheumatic disease: state of the art and future perspectives. Ann Rheum Dis 2010;69:2062–6. [4] Bykerk VP. Strategies to prevent rheumatoid arthritis in high-risk patients. Curr Opin Rheumatol 2011;23:179–84. [5] Tak P. Prevention of clinically manifest rheumatoid arthritis by B cell directed therapy in the earliest phase of the disease. Amsterdam: Dutch Cochrane Centre, Academisch Medisch Centrum 2012 [updated 23. 08. 2010; cited 18.07.2012] http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2442 [6] Majka DS, Holers VM. Can we accurately predict the development of rheumatoid arthritis in the preclinical phase? Arthritis Rheum 2003;48:2701–5.
We describe the case of a 68-year-old lady initially diagnosed with polymyalgia rhumatica after presenting with morning stiffness, proximal muscle aches and raised inflammatory markers. Despite appropriate treatment with prednisone, she developed marked synovitis of her wrists, metacarpophalangeal (MCP) joints and proximal interphalangeal (PIP) joints. The diagnosis was modified to rheumatoid arthritis (RA) in the setting of persistent morning stiffness, elevated inflammatory markers, typical erosive changes in the carpal bones on MRI and elevated anti-CCP2 levels (141 UI, normal < 50 UI). Despite treatment with methotrexate (15 mg weekly) and 15 mg of prednisone daily, the patient returned with increasing morning stiffness, diffuse joint pains, wrist swelling and inflammatory back pain. Clinical examination revealed marked right wrist synovitis, swelling of several MCP and PIP joints and the presence of erythematous lesions on her back and thighs. Spinal and sacroiliac (SI) palpation was diffusely painful and lumbar mobility was diminished, with a Schober of +3 cm. Inflammatory markers were significantly raised (CRP of 109 mg/L and ESR of 74 mmHg/h). A
Laboratoire Biomnis, 19, avenue Tony-Garnier, 69007 Lyon, France c Centre de radiologie diagnostique et interventionnelle, groupe IRIS, site du Confluent, 44277 Nantes, France d Service de médecine nucléaire, centre Catherine-de-Sienne, site du Confluent, 44277 Nantes, France
∗ Corresponding
author. Tel.: +33 6 31 05 99 81; fax: +33 2 28 25 51 59. E-mail address: [email protected] (O. Grossi) Accepted 28 February 2013 Available online 23 April 2013
doi:10.1016/j.jbspin.2013.02.015
Primary prevention of rheumatoid arthritis: A qualitative study in a high-risk population
a r t i c l e
i n f o
Keywords: Rheumatoid arthritis Primary prevention Qualitative study
First-degree relatives of patients with rheumatoid arthritis (RA) have a 4-fold to 5-fold increase in the risk of developing the disease [1]. Researchers are currently considering the development of strategies for preventing RA [2–5] and therefore for detecting high-risk individuals [6,7]. Here, our objectives were to determine:
673
• the expectations and level of interest of high-risk individuals regarding prophylactic interventions; • the desirable characteristics of prophylactic interventions, and; • the reasons that might lead individuals to participate in a randomized placebo-controlled trial. 1. Methods We used a qualitative approach to evaluate the opinions of candidates to primary RA prevention [8]. The study patients were individuals likely to be considered in the future for prophylactic treatment, i.e., first-degree relatives of RA patients. Face-to-face interviews lasting 30–45 minutes were conducted using a semi-structured interview guide. Additional details on the study methodology are available in the Appendix (Supplementary data). 2. Results We interviewed 20 first-degree relatives of RA patients (Appendix and Tables S1-S3, Supplementary data). Mean age was 45 years. Most of the participants (18/20) expressed interest in receiving prophylactic treatment should the results of screening tests indicate a high risk of developing RA. The cut-off above which participants said they would take prophylactic treatment was a 30% risk of developing RA within the next 5 years (Fig. 1). The participants usually expected that prophylactic therapy would consist in taking medications. However, a role for lifestyle changes and alternative medicines was also considered (Table 1). Although the main expectation was that the therapeutic intervention would prevent the development of RA (16/20), a treatment that would merely delay the development of RA was considered just as
Table 1 Main themes and subthemes identified by analysis of the interviews. Themes
Subthemes
Illustrative quotes
Representations of primary prevention interventions
Pharmacological intervention
Alternative medicines
“I think drugs would be involved, drugs that are less strong than those used to treat the disease.” (participant #2) “I envision preventive treatment involving nonmedical measures, for instance a special diet, participating in sports, or engaging in a specific lifestyle.” (participant #7) “I see this as natural medicines, such as devil’s claw.”
Expectations regarding primary prevention
To prevent the disease or delay its onset
“The preventive treatment should prevent the development of the disease. But if it only delays the disease, that’s better than nothing.” (participant #1)
Preferred route of administration
Oral route to avoid injections and to allow dosing at home
“Tablets are the simplest method.” (participant #4)
Lifestyle changes
Preference for a small number of doses
“Self-injection would not work for me.” (participant #19) “[. . .] If it’s an injection and I have to go somewhere to get it, since I work full time, that’s something I wouldn’t really like to do.” (participant #13) “It would have to be one dose every month or every week at the most. But not everyday.” (participant #10)
Possible barriers to accepting primary prevention
Adverse effects
“Finally, I would be willing to accept the risk of developing the disease, which is perhaps less burdensome than the drug.” “I prefer a drug that doesn’t affect the immune system [. . .] drugs can make us more vulnerable to infections.” (participant #15) “The problem is that getting sick at each dose is not compatible with working.” (participant #5)
Reasons for participating in a randomized trial
Feeling involved
“Well, I see so much suffering in my sister, so I think that if I can help with this study, then I’d be glad to.” (participant #9) “I would participate so that I would get the drug to prevent the disease from developing.” “I’d like to participate to help the researchers make progress.” (participant #10)
Expected personal benefit Altruism Barriers to participation in a randomized trial
Potential side effects Uncertainty about the true risk Placebo
“I’ve seen my sister and my brother. . ., there are diseases that develop because of drugs.” (participant #1) “For me, the problem is having to bother with taking drugs when we are healthy and not even sure we will get the disease.” (participant #18) “[. . .] I understand the role for the placebo in your studies, but to me it makes no sense.” (participant #13)
674
Letters to the Editor / Joint Bone Spine 80 (2013) 667–676 [7] Deane KD, Norris JM, Holers VM. Preclinical rheumatoid arthritis: identification, evaluation, and future directions for investigation. Rheum Dis Clin North Am 2010;36:213–41. [8] Hudelson P. La recherche qualitative en médecine de premier recours. Rev Med Suisse 2004;503:2497.
Fiona Novotny a Sylvie Haeny a Patricia Hudelson b Monica Escher c Axel Finckh d,e,∗ a Université de Genève, Geneva, Switzerland b Consultation Transculturelle et Interprétariat, Département de Médecine Communautaire, de premier recours et des urgences, Hôpitaux Universitaires de Genève, Geneva, Switzerland c Consultation douleur et soins palliatifs, Service de pharmacologie et toxicologie cliniques, Hôpitaux Universitaires de Genève, Geneva, Switzerland d Service de Rhumatologie, Hôpitaux Universitaires de Genève, 26, avenue Beau-Séjour, 1211 Geneva 14, Switzerland e Service d’Épidémiologie Clinique, Hôpitaux Universitaires de Genève, Geneva, Switzerland
Fig. 1. Theoretical risk of developing rheumatoid arthritis (RA) in the next 5 years above which high-risk individuals would be willing to take prophylactic treatment.
useful. The preferred route of administration was by mouth. A small number of doses was also considered crucial in the setting of primary prevention. Of the 20 participants, nine (40%) said they would choose parenteral treatment at widely spaced intervals and five (25%) daily oral treatment. Concern about serious adverse effects, most notably immune system impairment, was a limiting factor for many participants. Most of the interviewees report being willing to participate in a randomized placebo-controlled trial, evaluating the efficacy of primary prevention. Their motivations were a feeling of being involved, produced by having an affected relative, a desire to contribute to research, and hope for a possible personal benefit. In conclusion, the results of this study suggest that primary prevention of RA may meet the expectations of the target population, provided means are available for identifying individuals at high risk for developing the disease (≥30%). Minimal constraints and a good safety profile are crucial features of future prophylactic treatments. Participation in studies designed to develop prophylactic strategies for RA seems acceptable to the target population. Funding: This project received financial support from the Fonds National Suisse de la Recherche Scientifique [3200B0 120639/1–AF] and Fondation Rheumasearch.
∗ Corresponding
author. Service de Rhumatologie, Hôpitaux Universitaires de Genève, 26, avenue Beau-Séjour, 1211 Geneva 14, Switzerland. Fax: +41 22 382 3535. E-mail address: axel.fi[email protected] (A. Finckh) Accepted 27 March 2013 Available online 5 July 2013
doi:10.1016/j.jbspin.2013.05.005
Coexistence of seropositive rheumatoid arthritis and SAPHO syndrome
a r t i c l e Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
i n f o
Keywords: Rheumatoid arthritis SAPHO syndrome Anti-cyclic citrullinated protein antibodies (ACPA)
Appendix A. Supplementary data 1. Case report Supplementary data (appendix and Tables S1-S3) associated with this article can be found, in the online version, at http://www.sciencedirect.com and doi:10.1016/j.plantsci.2004. 08.011. References [1] Silman AJ, Hennessy E, Ollier B. Incidence of rheumatoid arthritis in a genetically predisposed population. Br J Rheumatol 1992;31:365–8. [2] Primary prevention of rheumatoid arthritis [Internet]. Current controlled trials. 2005 [cited 2007]. Available from: http://www.controlledtrials.com/mrct/trial/231203/Schaardenburg [3] Klareskog L, Gregersen PK, Huizinga TW. Prevention of autoimmune rheumatic disease: state of the art and future perspectives. Ann Rheum Dis 2010;69:2062–6. [4] Bykerk VP. Strategies to prevent rheumatoid arthritis in high-risk patients. Curr Opin Rheumatol 2011;23:179–84. [5] Tak P. Prevention of clinically manifest rheumatoid arthritis by B cell directed therapy in the earliest phase of the disease. Amsterdam: Dutch Cochrane Centre, Academisch Medisch Centrum 2012 [updated 23. 08. 2010; cited 18.07.2012] http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2442 [6] Majka DS, Holers VM. Can we accurately predict the development of rheumatoid arthritis in the preclinical phase? Arthritis Rheum 2003;48:2701–5.
We describe the case of a 68-year-old lady initially diagnosed with polymyalgia rhumatica after presenting with morning stiffness, proximal muscle aches and raised inflammatory markers. Despite appropriate treatment with prednisone, she developed marked synovitis of her wrists, metacarpophalangeal (MCP) joints and proximal interphalangeal (PIP) joints. The diagnosis was modified to rheumatoid arthritis (RA) in the setting of persistent morning stiffness, elevated inflammatory markers, typical erosive changes in the carpal bones on MRI and elevated anti-CCP2 levels (141 UI, normal < 50 UI). Despite treatment with methotrexate (15 mg weekly) and 15 mg of prednisone daily, the patient returned with increasing morning stiffness, diffuse joint pains, wrist swelling and inflammatory back pain. Clinical examination revealed marked right wrist synovitis, swelling of several MCP and PIP joints and the presence of erythematous lesions on her back and thighs. Spinal and sacroiliac (SI) palpation was diffusely painful and lumbar mobility was diminished, with a Schober of +3 cm. Inflammatory markers were significantly raised (CRP of 109 mg/L and ESR of 74 mmHg/h). A