Clinical Edge Journal Scan

Key clinical point: Contraceptive use among adolescents in the United States increased overall from 2006 to 2019, although consistent condom use declined.

Major finding: From 2006-2010 to 2015-2019, adolescents aged 15 to 19 years reported an 86% increased use of any contraception, a 26% increased use of multiple contraception methods, and a 3% increased use of IUDs or implants. 

Study details: The data come from a review of adolescents aged 15 to 19 years from the National Surveys of Family Growth, including 4,662 individuals from 2006-2010, 4,134 from 2011-2015, and 3,182 from 2015-2019.

Disclosures: The study was supported by an anonymous foundation. The researchers had no financial conflicts to disclose.

Source: Lindberg LD et al. Contraception: X. 2021 Apr 8. doi: 10.1016/j.conx.2021.100064.

Key clinical point: Contraceptive use among adolescents in the United States increased overall from 2006 to 2019, although consistent condom use declined.

Major finding: From 2006-2010 to 2015-2019, adolescents aged 15 to 19 years reported an 86% increased use of any contraception, a 26% increased use of multiple contraception methods, and a 3% increased use of IUDs or implants. 

Study details: The data come from a review of adolescents aged 15 to 19 years from the National Surveys of Family Growth, including 4,662 individuals from 2006-2010, 4,134 from 2011-2015, and 3,182 from 2015-2019.

Disclosures: The study was supported by an anonymous foundation. The researchers had no financial conflicts to disclose.

Source: Lindberg LD et al. Contraception: X. 2021 Apr 8. doi: 10.1016/j.conx.2021.100064.

Key clinical point: Contraceptive use among adolescents in the United States increased overall from 2006 to 2019, although consistent condom use declined.

Major finding: From 2006-2010 to 2015-2019, adolescents aged 15 to 19 years reported an 86% increased use of any contraception, a 26% increased use of multiple contraception methods, and a 3% increased use of IUDs or implants. 

Study details: The data come from a review of adolescents aged 15 to 19 years from the National Surveys of Family Growth, including 4,662 individuals from 2006-2010, 4,134 from 2011-2015, and 3,182 from 2015-2019.

Disclosures: The study was supported by an anonymous foundation. The researchers had no financial conflicts to disclose.

Source: Lindberg LD et al. Contraception: X. 2021 Apr 8. doi: 10.1016/j.conx.2021.100064.

Key clinical point: The generally positive attitudes towards contraception but low levels of use highlight the need for greater communication about behavior change among health professionals and medical students to increase their roles as change agents in their communities.

Major finding: Although 58% of the respondents were sexually active, only 18% were using a contraceptive at the time of the survey; however, 83% of contraceptive users were satisfied with past use. In addition, approximately half of respondents discussed contraception with their partners and four-fifths said they would encourage others in contraceptive use, although only 18% were involved in providing family planning methods.

Study details: The data come from a cross-sectional survey of 400 health workers and clinical care medical students in Ghana between January 1, 2018, and June 30, 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Agbeno EK et al. Int J Reprod Med. 2021 Mar 22. doi: 10.1155/2021/6631790. 

Key clinical point: The generally positive attitudes towards contraception but low levels of use highlight the need for greater communication about behavior change among health professionals and medical students to increase their roles as change agents in their communities.

Major finding: Although 58% of the respondents were sexually active, only 18% were using a contraceptive at the time of the survey; however, 83% of contraceptive users were satisfied with past use. In addition, approximately half of respondents discussed contraception with their partners and four-fifths said they would encourage others in contraceptive use, although only 18% were involved in providing family planning methods.

Study details: The data come from a cross-sectional survey of 400 health workers and clinical care medical students in Ghana between January 1, 2018, and June 30, 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Agbeno EK et al. Int J Reprod Med. 2021 Mar 22. doi: 10.1155/2021/6631790. 

Key clinical point: The generally positive attitudes towards contraception but low levels of use highlight the need for greater communication about behavior change among health professionals and medical students to increase their roles as change agents in their communities.

Major finding: Although 58% of the respondents were sexually active, only 18% were using a contraceptive at the time of the survey; however, 83% of contraceptive users were satisfied with past use. In addition, approximately half of respondents discussed contraception with their partners and four-fifths said they would encourage others in contraceptive use, although only 18% were involved in providing family planning methods.

Study details: The data come from a cross-sectional survey of 400 health workers and clinical care medical students in Ghana between January 1, 2018, and June 30, 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Agbeno EK et al. Int J Reprod Med. 2021 Mar 22. doi: 10.1155/2021/6631790. 

Key clinical point: Levonorgestrel was noninferior to copper IUD for emergency contraception, with similar pregnancy rates and adverse events reported for both methods.

Major finding: Pregnancy rates were 1 in 317 (0.3%) in the levonorgestrel group and 0 in 321 (0%) in the copper IUD group in the modified intent-to-treat analysis.

Study details: The data come from a randomized trial of 317 women who received levonorgestrel IUD and 321 who received copper IUDs and provided 1-month outcome data.

Disclosures: The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); the University of Utah, with funding in part from the National Institutes of Health (NIH) National Center for Research Resources and National Center for Advancing Translational Sciences; and grants to the lead author and several coauthors from the NIH Office of Research on Women’s Health and the Eunice Kennedy Shriver NICHD.

Source:  Turok DK et al.  N Engl J Med. 2021 Jan 28. doi: 10.1056/NEJMoa2022141.

Key clinical point: Levonorgestrel was noninferior to copper IUD for emergency contraception, with similar pregnancy rates and adverse events reported for both methods.

Major finding: Pregnancy rates were 1 in 317 (0.3%) in the levonorgestrel group and 0 in 321 (0%) in the copper IUD group in the modified intent-to-treat analysis.

Study details: The data come from a randomized trial of 317 women who received levonorgestrel IUD and 321 who received copper IUDs and provided 1-month outcome data.

Disclosures: The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); the University of Utah, with funding in part from the National Institutes of Health (NIH) National Center for Research Resources and National Center for Advancing Translational Sciences; and grants to the lead author and several coauthors from the NIH Office of Research on Women’s Health and the Eunice Kennedy Shriver NICHD.

Source:  Turok DK et al.  N Engl J Med. 2021 Jan 28. doi: 10.1056/NEJMoa2022141.

Key clinical point: Levonorgestrel was noninferior to copper IUD for emergency contraception, with similar pregnancy rates and adverse events reported for both methods.

Major finding: Pregnancy rates were 1 in 317 (0.3%) in the levonorgestrel group and 0 in 321 (0%) in the copper IUD group in the modified intent-to-treat analysis.

Study details: The data come from a randomized trial of 317 women who received levonorgestrel IUD and 321 who received copper IUDs and provided 1-month outcome data.

Disclosures: The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); the University of Utah, with funding in part from the National Institutes of Health (NIH) National Center for Research Resources and National Center for Advancing Translational Sciences; and grants to the lead author and several coauthors from the NIH Office of Research on Women’s Health and the Eunice Kennedy Shriver NICHD.

Source:  Turok DK et al.  N Engl J Med. 2021 Jan 28. doi: 10.1056/NEJMoa2022141.

Key clinical point: Use of progestin-only contraception was associated with greater breast hypertrophy and pain in adolescents with macromastia.

Major finding: Compared to controls, macromastia patients who used progestin-only contraceptives were 500% more likely to report breast pain (odds ratio 4.94); macromastia patients who used progestin-only contraception also had significantly more breast tissue resected during mammaplasty and greater musculoskeletal pain. 

Study details: The data come from a retrospective study of 378 macromastia patients aged 12 to 21 years and 378 controls; 5.3% of macromastia patients and 28.0% of controls used progestin-only contraception.

Disclosures: The study was supported in part by the Plastic Surgery Foundation. The researchers had no financial conflicts to disclose.

Source: Nuzzi LC et al. Plast Reconstr Surg Glob Open. 2021 Feb 12. doi: 10.1097/GOX.0000000000003421.

Key clinical point: Use of progestin-only contraception was associated with greater breast hypertrophy and pain in adolescents with macromastia.

Major finding: Compared to controls, macromastia patients who used progestin-only contraceptives were 500% more likely to report breast pain (odds ratio 4.94); macromastia patients who used progestin-only contraception also had significantly more breast tissue resected during mammaplasty and greater musculoskeletal pain. 

Study details: The data come from a retrospective study of 378 macromastia patients aged 12 to 21 years and 378 controls; 5.3% of macromastia patients and 28.0% of controls used progestin-only contraception.

Disclosures: The study was supported in part by the Plastic Surgery Foundation. The researchers had no financial conflicts to disclose.

Source: Nuzzi LC et al. Plast Reconstr Surg Glob Open. 2021 Feb 12. doi: 10.1097/GOX.0000000000003421.

Key clinical point: Use of progestin-only contraception was associated with greater breast hypertrophy and pain in adolescents with macromastia.

Major finding: Compared to controls, macromastia patients who used progestin-only contraceptives were 500% more likely to report breast pain (odds ratio 4.94); macromastia patients who used progestin-only contraception also had significantly more breast tissue resected during mammaplasty and greater musculoskeletal pain. 

Study details: The data come from a retrospective study of 378 macromastia patients aged 12 to 21 years and 378 controls; 5.3% of macromastia patients and 28.0% of controls used progestin-only contraception.

Disclosures: The study was supported in part by the Plastic Surgery Foundation. The researchers had no financial conflicts to disclose.

Source: Nuzzi LC et al. Plast Reconstr Surg Glob Open. 2021 Feb 12. doi: 10.1097/GOX.0000000000003421.

Key clinical point: Among healthy young women taking oral contraceptives, pulse wave velocity was lower in active women compared with inactive women, suggesting that physical activity may mitigate the risk of arterial stiffness associated with OC use.   

Major finding: Pulse wave velocity as an indicator of arterial stiffness was similar in oral contraceptive users and non-users, however, PWV was significantly lower in active women vs. inactive women (5.4 ms ^-1 vs. 6.3 ms ^-1).

Study details: The data come from a cross-sectional study of 49 healthy young women with an average age of 21.9 years, divided into four groups (inactive vs. active, OC use vs. non-OC use).

Disclosures: The study was supported in part by the European Union and the New Aquitaine region through the Habisan program (CPER-FEDER). The researchers had no financial conflicts to disclose.

Source: Enea C et al. Int J Environ Res Public Health. 2021 Mar 25. doi: 10.3390/ijerph18073393.

Key clinical point: Among healthy young women taking oral contraceptives, pulse wave velocity was lower in active women compared with inactive women, suggesting that physical activity may mitigate the risk of arterial stiffness associated with OC use.   

Major finding: Pulse wave velocity as an indicator of arterial stiffness was similar in oral contraceptive users and non-users, however, PWV was significantly lower in active women vs. inactive women (5.4 ms ^-1 vs. 6.3 ms ^-1).

Study details: The data come from a cross-sectional study of 49 healthy young women with an average age of 21.9 years, divided into four groups (inactive vs. active, OC use vs. non-OC use).

Disclosures: The study was supported in part by the European Union and the New Aquitaine region through the Habisan program (CPER-FEDER). The researchers had no financial conflicts to disclose.

Source: Enea C et al. Int J Environ Res Public Health. 2021 Mar 25. doi: 10.3390/ijerph18073393.

Key clinical point: Among healthy young women taking oral contraceptives, pulse wave velocity was lower in active women compared with inactive women, suggesting that physical activity may mitigate the risk of arterial stiffness associated with OC use.   

Major finding: Pulse wave velocity as an indicator of arterial stiffness was similar in oral contraceptive users and non-users, however, PWV was significantly lower in active women vs. inactive women (5.4 ms ^-1 vs. 6.3 ms ^-1).

Study details: The data come from a cross-sectional study of 49 healthy young women with an average age of 21.9 years, divided into four groups (inactive vs. active, OC use vs. non-OC use).

Disclosures: The study was supported in part by the European Union and the New Aquitaine region through the Habisan program (CPER-FEDER). The researchers had no financial conflicts to disclose.

Source: Enea C et al. Int J Environ Res Public Health. 2021 Mar 25. doi: 10.3390/ijerph18073393.

Key clinical point: In a biomechanical ex vivo analysis, metal uterine sounds caused uterine perforation, but the manufacturer’s plastic intrauterine device placement rod did not.

Major finding: The lowest mean maximum force generated for IUD placement was 12.3 Newtons with the levonorgestrel intrauterine system placement instrument, followed by 14.1 Newtons with the copper T380A intrauterine device placement instrument 14.1 Newtons; the highest mean maximum force of 17.9 N occurred with the metal sound (P < 0.01).

Study details: The data come from 16 premenopausal women with benign conditions who provided hysterectomy sections at a single center.

Disclosures: The study was funded indirectly through grants to the University of Utah from Bayer, Bioceptive, Sebela, Medicines 360, Merck, and Cooper Surgical. Lead author Dr. Duncan had no financial conflicts to disclose.

Source: Duncan J et al. BMC Womens Health. 2021 Apr 7. doi: 10.1186/s12905-021-01285-6.

Key clinical point: In a biomechanical ex vivo analysis, metal uterine sounds caused uterine perforation, but the manufacturer’s plastic intrauterine device placement rod did not.

Major finding: The lowest mean maximum force generated for IUD placement was 12.3 Newtons with the levonorgestrel intrauterine system placement instrument, followed by 14.1 Newtons with the copper T380A intrauterine device placement instrument 14.1 Newtons; the highest mean maximum force of 17.9 N occurred with the metal sound (P < 0.01).

Study details: The data come from 16 premenopausal women with benign conditions who provided hysterectomy sections at a single center.

Disclosures: The study was funded indirectly through grants to the University of Utah from Bayer, Bioceptive, Sebela, Medicines 360, Merck, and Cooper Surgical. Lead author Dr. Duncan had no financial conflicts to disclose.

Source: Duncan J et al. BMC Womens Health. 2021 Apr 7. doi: 10.1186/s12905-021-01285-6.

Key clinical point: In a biomechanical ex vivo analysis, metal uterine sounds caused uterine perforation, but the manufacturer’s plastic intrauterine device placement rod did not.

Major finding: The lowest mean maximum force generated for IUD placement was 12.3 Newtons with the levonorgestrel intrauterine system placement instrument, followed by 14.1 Newtons with the copper T380A intrauterine device placement instrument 14.1 Newtons; the highest mean maximum force of 17.9 N occurred with the metal sound (P < 0.01).

Study details: The data come from 16 premenopausal women with benign conditions who provided hysterectomy sections at a single center.

Disclosures: The study was funded indirectly through grants to the University of Utah from Bayer, Bioceptive, Sebela, Medicines 360, Merck, and Cooper Surgical. Lead author Dr. Duncan had no financial conflicts to disclose.

Source: Duncan J et al. BMC Womens Health. 2021 Apr 7. doi: 10.1186/s12905-021-01285-6.

Key clinical point: Use of oral contraceptives by women of reproductive age was not associated with increased risk of heart failure later in life, but the potential impact of different formulations and dosages deserves further research.

Major finding:  Over an average of 12 years’ follow-up, the researchers identified 138 incident cases of heart failure. The incidence of heart failure was not significantly associated with heart failure in multivariate analysis (hazard ratio 0.96); however, any OC use was positively associated with left ventricular end-diastolic mass (P = 0.006) and stroke volume (P = 0.01 and P = 0.005 for left and right ventricles, respectively).

Study details: The data come from a retrospective study of 3,594 women with an average age of 62 years who were enrolled in the Multi‐Ethnic Study of Atherosclerosis and could provide data on oral contraceptive use.

Disclosures: The study was supported by the Guangdong Peak Project, the Science and Technology Planning Project of Guangdong Province, Natural Science Foundation of Guangdong Province, and the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

Source: Luo D et al. ESC Heart Fail. 2021 Apr 9. doi: 10.1002/ehf2.13328.

Key clinical point: Use of oral contraceptives by women of reproductive age was not associated with increased risk of heart failure later in life, but the potential impact of different formulations and dosages deserves further research.

Major finding:  Over an average of 12 years’ follow-up, the researchers identified 138 incident cases of heart failure. The incidence of heart failure was not significantly associated with heart failure in multivariate analysis (hazard ratio 0.96); however, any OC use was positively associated with left ventricular end-diastolic mass (P = 0.006) and stroke volume (P = 0.01 and P = 0.005 for left and right ventricles, respectively).

Study details: The data come from a retrospective study of 3,594 women with an average age of 62 years who were enrolled in the Multi‐Ethnic Study of Atherosclerosis and could provide data on oral contraceptive use.

Disclosures: The study was supported by the Guangdong Peak Project, the Science and Technology Planning Project of Guangdong Province, Natural Science Foundation of Guangdong Province, and the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

Source: Luo D et al. ESC Heart Fail. 2021 Apr 9. doi: 10.1002/ehf2.13328.

Key clinical point: Use of oral contraceptives by women of reproductive age was not associated with increased risk of heart failure later in life, but the potential impact of different formulations and dosages deserves further research.

Major finding:  Over an average of 12 years’ follow-up, the researchers identified 138 incident cases of heart failure. The incidence of heart failure was not significantly associated with heart failure in multivariate analysis (hazard ratio 0.96); however, any OC use was positively associated with left ventricular end-diastolic mass (P = 0.006) and stroke volume (P = 0.01 and P = 0.005 for left and right ventricles, respectively).

Study details: The data come from a retrospective study of 3,594 women with an average age of 62 years who were enrolled in the Multi‐Ethnic Study of Atherosclerosis and could provide data on oral contraceptive use.

Disclosures: The study was supported by the Guangdong Peak Project, the Science and Technology Planning Project of Guangdong Province, Natural Science Foundation of Guangdong Province, and the National Key Research and Development Program of China. The researchers had no financial conflicts to disclose.

Source: Luo D et al. ESC Heart Fail. 2021 Apr 9. doi: 10.1002/ehf2.13328.

In a study by Trembely et al. sponsored by Pfizer, an indirect comparison of both studies was performed using a simulated treatment comparison to account for differences in patient characteristics. As expected, the overall response rates were higher in the venetoclax study compared to the glasdegib study (48% vs. 24%), but overall survival was similar (hazard ratio 0.75 vs. HR 0.46). This study demonstrates again that CR/CRi cannot be used as a surrogate endpoint for survival in AML. In addition, with the negative study of V-LDAC vs. LDAC and the improved overall survival of the combination of azacytidine + venetoclax (Aza-ven) vs. azacitdine, the current standard of care of newly diagnosed patients with AML unbale to tolerate intensive chemotherapy is Aza-ven and V-LDAC is rarely used.

The success of Aza-ven is not without side effects. This was demonstrated recently in a retrospective study by Feld et al. In that study 72 patients with newly diagnosed AML (26), relapsed refractory AML (39) and MDS (7) received azacitdine + venetoclax. The main side effect was myelosuppression with only 15% of patients who were transfusion dependent become transfusion independent. In addition, 46% of patients had a neutropenic fever and 43.7% of patients requiring admission. Most patients (54.9%) required treatment interruption and 35.2% stopped venetoclax for toxicity.

This study highlighted that the optimal dose and frequency of venetoclax remains unclear. A shorted duration or lower dose of venetoclax maybe more ideal, however that may lead to less efficacy. In addition, bone marrow evaluation to assess for cellularity on D21 to D28 of the first cycle may help guide dose adjustments. Finally with the high CR/CRi rates in AML and short duration of response further studies are ongoing to further define molecular abnormalities that may refine prognosis or guide therapy. Two of those studies recently reported identified a prognostic and possible therapeutic role for both EZH2 and the PI3 kinase mTOR pathway.

In a study by Trembely et al. sponsored by Pfizer, an indirect comparison of both studies was performed using a simulated treatment comparison to account for differences in patient characteristics. As expected, the overall response rates were higher in the venetoclax study compared to the glasdegib study (48% vs. 24%), but overall survival was similar (hazard ratio 0.75 vs. HR 0.46). This study demonstrates again that CR/CRi cannot be used as a surrogate endpoint for survival in AML. In addition, with the negative study of V-LDAC vs. LDAC and the improved overall survival of the combination of azacytidine + venetoclax (Aza-ven) vs. azacitdine, the current standard of care of newly diagnosed patients with AML unbale to tolerate intensive chemotherapy is Aza-ven and V-LDAC is rarely used.

The success of Aza-ven is not without side effects. This was demonstrated recently in a retrospective study by Feld et al. In that study 72 patients with newly diagnosed AML (26), relapsed refractory AML (39) and MDS (7) received azacitdine + venetoclax. The main side effect was myelosuppression with only 15% of patients who were transfusion dependent become transfusion independent. In addition, 46% of patients had a neutropenic fever and 43.7% of patients requiring admission. Most patients (54.9%) required treatment interruption and 35.2% stopped venetoclax for toxicity.

This study highlighted that the optimal dose and frequency of venetoclax remains unclear. A shorted duration or lower dose of venetoclax maybe more ideal, however that may lead to less efficacy. In addition, bone marrow evaluation to assess for cellularity on D21 to D28 of the first cycle may help guide dose adjustments. Finally with the high CR/CRi rates in AML and short duration of response further studies are ongoing to further define molecular abnormalities that may refine prognosis or guide therapy. Two of those studies recently reported identified a prognostic and possible therapeutic role for both EZH2 and the PI3 kinase mTOR pathway.

In a study by Trembely et al. sponsored by Pfizer, an indirect comparison of both studies was performed using a simulated treatment comparison to account for differences in patient characteristics. As expected, the overall response rates were higher in the venetoclax study compared to the glasdegib study (48% vs. 24%), but overall survival was similar (hazard ratio 0.75 vs. HR 0.46). This study demonstrates again that CR/CRi cannot be used as a surrogate endpoint for survival in AML. In addition, with the negative study of V-LDAC vs. LDAC and the improved overall survival of the combination of azacytidine + venetoclax (Aza-ven) vs. azacitdine, the current standard of care of newly diagnosed patients with AML unbale to tolerate intensive chemotherapy is Aza-ven and V-LDAC is rarely used.

The success of Aza-ven is not without side effects. This was demonstrated recently in a retrospective study by Feld et al. In that study 72 patients with newly diagnosed AML (26), relapsed refractory AML (39) and MDS (7) received azacitdine + venetoclax. The main side effect was myelosuppression with only 15% of patients who were transfusion dependent become transfusion independent. In addition, 46% of patients had a neutropenic fever and 43.7% of patients requiring admission. Most patients (54.9%) required treatment interruption and 35.2% stopped venetoclax for toxicity.

This study highlighted that the optimal dose and frequency of venetoclax remains unclear. A shorted duration or lower dose of venetoclax maybe more ideal, however that may lead to less efficacy. In addition, bone marrow evaluation to assess for cellularity on D21 to D28 of the first cycle may help guide dose adjustments. Finally with the high CR/CRi rates in AML and short duration of response further studies are ongoing to further define molecular abnormalities that may refine prognosis or guide therapy. Two of those studies recently reported identified a prognostic and possible therapeutic role for both EZH2 and the PI3 kinase mTOR pathway.

Iguratimod (IGU) is a novel small-molecule synthetic DMARD being studied for RA; its exact mechanism is unknown, but it inhibits NF-kB activation and seems to reduce bone resorption via RANKL and cartilage erosion via matrix metalloproteinases. Currently, it is approved in Japan and China for treatment of RA; initial studies from 2008-2010 showed improved ACR20 rates compared to placebo and comparable rates with methotrexate monotherapy; combination therapy with methotrexate appears to be more effective than either methotrexate or IGU monotherapy. Yoshikawa et al present a small study of 47 patients receiving methotrexate or methotrexate with IGU and show promising results regarding tapering of methotrexate with sustained remission/low disease activity and decrease in ultrasound evidence of synovitis in patients receiving IGU, suggesting that it is a reasonable longer-term option for RA patients. However, the medication is not approved in the US, nor have studies in patients in the US been published, so generalizability in patients outside of Japan and China is uncertain, in addition to concerns related to the small sample size.

In contrast, tocilizumab is an established therapy for RA; Pappas et al present real-world clinical practice data from the Corrona RA registry. Among nearly 1800 RA patients who initiated tocilizumab therapy, the mean durability of response was over 3 years in terms of maintaining minimum clinically important difference (MCID) over baseline CDAI and over 1 year in terms of maintaining low disease activity. Most patients in the study had previously received biologic therapy. Though the observational nature of the study limits its generalizability, the addition of efficacy data to persistence on therapy lend weight to this evidence regarding durability of response to tocilizumab, as the proportion of patients maintaining MCID was >50% at 3 years.

Treatment options are limited for RA patients who have ILD or other pulmonary complications. The fear of causing or exacerbating pulmonary toxicity limits the use of methotrexate, leflunomide, and anti-TNF biologics. Some data support the safety of rituximab and abatacept. A retrospective observational study looked at outcomes in RA patients on rituximab and JAK inhibitors. Reassuringly, respiratory event rates were no different between the two groups though number of patients and trial design prevents wider generalization; it is also unknown whether RA-ILD improves with ritixumab or JAK-inhibition. However, given these results, studying JAK inhibitors in larger prospective studies would be reasonable.

Iguratimod (IGU) is a novel small-molecule synthetic DMARD being studied for RA; its exact mechanism is unknown, but it inhibits NF-kB activation and seems to reduce bone resorption via RANKL and cartilage erosion via matrix metalloproteinases. Currently, it is approved in Japan and China for treatment of RA; initial studies from 2008-2010 showed improved ACR20 rates compared to placebo and comparable rates with methotrexate monotherapy; combination therapy with methotrexate appears to be more effective than either methotrexate or IGU monotherapy. Yoshikawa et al present a small study of 47 patients receiving methotrexate or methotrexate with IGU and show promising results regarding tapering of methotrexate with sustained remission/low disease activity and decrease in ultrasound evidence of synovitis in patients receiving IGU, suggesting that it is a reasonable longer-term option for RA patients. However, the medication is not approved in the US, nor have studies in patients in the US been published, so generalizability in patients outside of Japan and China is uncertain, in addition to concerns related to the small sample size.

In contrast, tocilizumab is an established therapy for RA; Pappas et al present real-world clinical practice data from the Corrona RA registry. Among nearly 1800 RA patients who initiated tocilizumab therapy, the mean durability of response was over 3 years in terms of maintaining minimum clinically important difference (MCID) over baseline CDAI and over 1 year in terms of maintaining low disease activity. Most patients in the study had previously received biologic therapy. Though the observational nature of the study limits its generalizability, the addition of efficacy data to persistence on therapy lend weight to this evidence regarding durability of response to tocilizumab, as the proportion of patients maintaining MCID was >50% at 3 years.

Treatment options are limited for RA patients who have ILD or other pulmonary complications. The fear of causing or exacerbating pulmonary toxicity limits the use of methotrexate, leflunomide, and anti-TNF biologics. Some data support the safety of rituximab and abatacept. A retrospective observational study looked at outcomes in RA patients on rituximab and JAK inhibitors. Reassuringly, respiratory event rates were no different between the two groups though number of patients and trial design prevents wider generalization; it is also unknown whether RA-ILD improves with ritixumab or JAK-inhibition. However, given these results, studying JAK inhibitors in larger prospective studies would be reasonable.

Iguratimod (IGU) is a novel small-molecule synthetic DMARD being studied for RA; its exact mechanism is unknown, but it inhibits NF-kB activation and seems to reduce bone resorption via RANKL and cartilage erosion via matrix metalloproteinases. Currently, it is approved in Japan and China for treatment of RA; initial studies from 2008-2010 showed improved ACR20 rates compared to placebo and comparable rates with methotrexate monotherapy; combination therapy with methotrexate appears to be more effective than either methotrexate or IGU monotherapy. Yoshikawa et al present a small study of 47 patients receiving methotrexate or methotrexate with IGU and show promising results regarding tapering of methotrexate with sustained remission/low disease activity and decrease in ultrasound evidence of synovitis in patients receiving IGU, suggesting that it is a reasonable longer-term option for RA patients. However, the medication is not approved in the US, nor have studies in patients in the US been published, so generalizability in patients outside of Japan and China is uncertain, in addition to concerns related to the small sample size.

In contrast, tocilizumab is an established therapy for RA; Pappas et al present real-world clinical practice data from the Corrona RA registry. Among nearly 1800 RA patients who initiated tocilizumab therapy, the mean durability of response was over 3 years in terms of maintaining minimum clinically important difference (MCID) over baseline CDAI and over 1 year in terms of maintaining low disease activity. Most patients in the study had previously received biologic therapy. Though the observational nature of the study limits its generalizability, the addition of efficacy data to persistence on therapy lend weight to this evidence regarding durability of response to tocilizumab, as the proportion of patients maintaining MCID was >50% at 3 years.

Treatment options are limited for RA patients who have ILD or other pulmonary complications. The fear of causing or exacerbating pulmonary toxicity limits the use of methotrexate, leflunomide, and anti-TNF biologics. Some data support the safety of rituximab and abatacept. A retrospective observational study looked at outcomes in RA patients on rituximab and JAK inhibitors. Reassuringly, respiratory event rates were no different between the two groups though number of patients and trial design prevents wider generalization; it is also unknown whether RA-ILD improves with ritixumab or JAK-inhibition. However, given these results, studying JAK inhibitors in larger prospective studies would be reasonable.

Key clinical point: Considerable proportions of cases with rheumatoid arthritis (RA) are still difficult to treat in real world despite intensive treatment.

Major finding: Among patients with RA, 10.1% were categorized as having difficult-to-treat RA despite being treated intensively. Main reasons for difficulty in treating RA were multidrug resistance (34.1%), comorbidities (9.8%), and socioeconomic reasons (56.1%).

Study details: Data come from an analysis of 1,709 patients with RA who visited Keio University Hospital between 2016 and 2017.

Disclosures: The study did not receive any funding. S Takanashi reported no conflicts of interest. Y Kaneko and T Takeuchi reported receiving grants or speaker fees from various sources.

Source: Takanashi S et al. Rheumatology (Oxford). 2021 Mar 2. doi: 10.1093/rheumatology/keab209.

Key clinical point: Considerable proportions of cases with rheumatoid arthritis (RA) are still difficult to treat in real world despite intensive treatment.

Major finding: Among patients with RA, 10.1% were categorized as having difficult-to-treat RA despite being treated intensively. Main reasons for difficulty in treating RA were multidrug resistance (34.1%), comorbidities (9.8%), and socioeconomic reasons (56.1%).

Study details: Data come from an analysis of 1,709 patients with RA who visited Keio University Hospital between 2016 and 2017.

Disclosures: The study did not receive any funding. S Takanashi reported no conflicts of interest. Y Kaneko and T Takeuchi reported receiving grants or speaker fees from various sources.

Source: Takanashi S et al. Rheumatology (Oxford). 2021 Mar 2. doi: 10.1093/rheumatology/keab209.

Key clinical point: Considerable proportions of cases with rheumatoid arthritis (RA) are still difficult to treat in real world despite intensive treatment.

Major finding: Among patients with RA, 10.1% were categorized as having difficult-to-treat RA despite being treated intensively. Main reasons for difficulty in treating RA were multidrug resistance (34.1%), comorbidities (9.8%), and socioeconomic reasons (56.1%).

Study details: Data come from an analysis of 1,709 patients with RA who visited Keio University Hospital between 2016 and 2017.

Disclosures: The study did not receive any funding. S Takanashi reported no conflicts of interest. Y Kaneko and T Takeuchi reported receiving grants or speaker fees from various sources.

Source: Takanashi S et al. Rheumatology (Oxford). 2021 Mar 2. doi: 10.1093/rheumatology/keab209.