Rheumatoid Arthritis

Key clinical point: Methotrexate reduced the risk for overall mortality in rheumatoid arthritis (RA), particularly mortality from RA with cardiovascular diseases and RA-associated interstitial lung diseases.

Major finding: Methotrexate significantly reduced risk for overall mortality by 41% (hazard ratio [HR] 0.59; P < .001), mortality from RA with cardiovascular disease by 28% (HR 0.72; P = .031), and mortality from RA-associated interstitial lung diseases by 56% (HR 0.44; P = .037).

Study details: Findings are from a meta-analysis of 15 cohort studies involving 69,914 participants.

Disclosures: The study was supported by grants from the National Natural Science Foundation of China and others. The authors declared no conflicts of interest.

Source: Xu J et al. Methotrexate use reduces mortality risk in rheumatoid arthritis: A systematic review and meta-analysis of cohort studies. Semin Arthritis Rheum. 2022;55:152031 (Jun 4). Doi: 10.1016/j.semarthrit.2022.152031

Key clinical point: Methotrexate reduced the risk for overall mortality in rheumatoid arthritis (RA), particularly mortality from RA with cardiovascular diseases and RA-associated interstitial lung diseases.

Major finding: Methotrexate significantly reduced risk for overall mortality by 41% (hazard ratio [HR] 0.59; P < .001), mortality from RA with cardiovascular disease by 28% (HR 0.72; P = .031), and mortality from RA-associated interstitial lung diseases by 56% (HR 0.44; P = .037).

Study details: Findings are from a meta-analysis of 15 cohort studies involving 69,914 participants.

Disclosures: The study was supported by grants from the National Natural Science Foundation of China and others. The authors declared no conflicts of interest.

Source: Xu J et al. Methotrexate use reduces mortality risk in rheumatoid arthritis: A systematic review and meta-analysis of cohort studies. Semin Arthritis Rheum. 2022;55:152031 (Jun 4). Doi: 10.1016/j.semarthrit.2022.152031

Key clinical point: Methotrexate reduced the risk for overall mortality in rheumatoid arthritis (RA), particularly mortality from RA with cardiovascular diseases and RA-associated interstitial lung diseases.

Major finding: Methotrexate significantly reduced risk for overall mortality by 41% (hazard ratio [HR] 0.59; P < .001), mortality from RA with cardiovascular disease by 28% (HR 0.72; P = .031), and mortality from RA-associated interstitial lung diseases by 56% (HR 0.44; P = .037).

Study details: Findings are from a meta-analysis of 15 cohort studies involving 69,914 participants.

Disclosures: The study was supported by grants from the National Natural Science Foundation of China and others. The authors declared no conflicts of interest.

Source: Xu J et al. Methotrexate use reduces mortality risk in rheumatoid arthritis: A systematic review and meta-analysis of cohort studies. Semin Arthritis Rheum. 2022;55:152031 (Jun 4). Doi: 10.1016/j.semarthrit.2022.152031

Key clinical point: Genetic liability to rheumatoid arthritis (RA) was positively associated with the risk for coronary artery disease (CAD) and intracerebral hemorrhage (IA), with the high levels of C-reactive protein (CRP) appearing to mediate the association with CAD.

Major finding: Each unit increase in log odds of RA increased the risk for CAD (combined odds ratio [cOR] 1.02; P = .003) and IA (cOR 1.05; P = .001), with the levels of genetically predicted CRP influencing the risk association between RA and CAD (adjusted cOR 1.01; P = .268).

Study details: This was a two-sample Mendelian randomization study that selected 70 single nucleotide polymorphisms strongly associated with RA from a genome-wide association meta-analysis including 14,361 patients with RA and 43,923 control individuals.

Disclosures: The study was supported by research grants from Swedish Heart-Lung Foundation, the Swedish Research Council for Health, and others. The authors declared no conflicts of interest.

Source: Yuan S et al. Genetic liability to rheumatoid arthritis in relation to coronary artery disease and stroke risk. Arthritis Rheumatol. 2022 (May 18). Doi: 10.1002/art.42239

Key clinical point: Genetic liability to rheumatoid arthritis (RA) was positively associated with the risk for coronary artery disease (CAD) and intracerebral hemorrhage (IA), with the high levels of C-reactive protein (CRP) appearing to mediate the association with CAD.

Major finding: Each unit increase in log odds of RA increased the risk for CAD (combined odds ratio [cOR] 1.02; P = .003) and IA (cOR 1.05; P = .001), with the levels of genetically predicted CRP influencing the risk association between RA and CAD (adjusted cOR 1.01; P = .268).

Study details: This was a two-sample Mendelian randomization study that selected 70 single nucleotide polymorphisms strongly associated with RA from a genome-wide association meta-analysis including 14,361 patients with RA and 43,923 control individuals.

Disclosures: The study was supported by research grants from Swedish Heart-Lung Foundation, the Swedish Research Council for Health, and others. The authors declared no conflicts of interest.

Source: Yuan S et al. Genetic liability to rheumatoid arthritis in relation to coronary artery disease and stroke risk. Arthritis Rheumatol. 2022 (May 18). Doi: 10.1002/art.42239

Key clinical point: Genetic liability to rheumatoid arthritis (RA) was positively associated with the risk for coronary artery disease (CAD) and intracerebral hemorrhage (IA), with the high levels of C-reactive protein (CRP) appearing to mediate the association with CAD.

Major finding: Each unit increase in log odds of RA increased the risk for CAD (combined odds ratio [cOR] 1.02; P = .003) and IA (cOR 1.05; P = .001), with the levels of genetically predicted CRP influencing the risk association between RA and CAD (adjusted cOR 1.01; P = .268).

Study details: This was a two-sample Mendelian randomization study that selected 70 single nucleotide polymorphisms strongly associated with RA from a genome-wide association meta-analysis including 14,361 patients with RA and 43,923 control individuals.

Disclosures: The study was supported by research grants from Swedish Heart-Lung Foundation, the Swedish Research Council for Health, and others. The authors declared no conflicts of interest.

Source: Yuan S et al. Genetic liability to rheumatoid arthritis in relation to coronary artery disease and stroke risk. Arthritis Rheumatol. 2022 (May 18). Doi: 10.1002/art.42239

Key clinical point: This real-world study found no evidence of increased risk for malignancy in patients with rheumatoid arthritis (RA) who initiated tofacitinib vs. tumor necrosis factor inhibitors (TNFi).

Major finding: The risk for cumulative malignancies in patients who initiated tofacitinib vs. TNFi was not higher in the real-world evidence (RWE) cohort (pooled weighted hazard ratio [pwHR] 1.01; 95% CI 0.83-1.22), but was numerically higher in the randomized controlled trial (RCT)-duplicate cohort of patients aged ≥50 years with at least one cardiovascular risk factor (pwHR 1.17; 95% CI 0.85-1.62).

Study details: This was a population-based observational, STAR-RA, study including 83,295 patients in the RWE cohort and 27,035 patients in the RCT-duplicate cohort who initiated tofacitinib or TNFi.

Disclosures: The study was supported by the Brigham and Women’s Hospital & Harvard Medical School (BWHHMS). SC Kim and RJ Desai reported receiving research grants to BWHHMS from various sources.

Source: Khosrow-Khavar F et al. Tofacitinib and risk of malignancy: Results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) Study. Arthritis Rheumatol. 2022 (May 29). Doi: 10.1002/art.42250

Key clinical point: This real-world study found no evidence of increased risk for malignancy in patients with rheumatoid arthritis (RA) who initiated tofacitinib vs. tumor necrosis factor inhibitors (TNFi).

Major finding: The risk for cumulative malignancies in patients who initiated tofacitinib vs. TNFi was not higher in the real-world evidence (RWE) cohort (pooled weighted hazard ratio [pwHR] 1.01; 95% CI 0.83-1.22), but was numerically higher in the randomized controlled trial (RCT)-duplicate cohort of patients aged ≥50 years with at least one cardiovascular risk factor (pwHR 1.17; 95% CI 0.85-1.62).

Study details: This was a population-based observational, STAR-RA, study including 83,295 patients in the RWE cohort and 27,035 patients in the RCT-duplicate cohort who initiated tofacitinib or TNFi.

Disclosures: The study was supported by the Brigham and Women’s Hospital & Harvard Medical School (BWHHMS). SC Kim and RJ Desai reported receiving research grants to BWHHMS from various sources.

Source: Khosrow-Khavar F et al. Tofacitinib and risk of malignancy: Results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) Study. Arthritis Rheumatol. 2022 (May 29). Doi: 10.1002/art.42250

Key clinical point: This real-world study found no evidence of increased risk for malignancy in patients with rheumatoid arthritis (RA) who initiated tofacitinib vs. tumor necrosis factor inhibitors (TNFi).

Major finding: The risk for cumulative malignancies in patients who initiated tofacitinib vs. TNFi was not higher in the real-world evidence (RWE) cohort (pooled weighted hazard ratio [pwHR] 1.01; 95% CI 0.83-1.22), but was numerically higher in the randomized controlled trial (RCT)-duplicate cohort of patients aged ≥50 years with at least one cardiovascular risk factor (pwHR 1.17; 95% CI 0.85-1.62).

Study details: This was a population-based observational, STAR-RA, study including 83,295 patients in the RWE cohort and 27,035 patients in the RCT-duplicate cohort who initiated tofacitinib or TNFi.

Disclosures: The study was supported by the Brigham and Women’s Hospital & Harvard Medical School (BWHHMS). SC Kim and RJ Desai reported receiving research grants to BWHHMS from various sources.

Source: Khosrow-Khavar F et al. Tofacitinib and risk of malignancy: Results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) Study. Arthritis Rheumatol. 2022 (May 29). Doi: 10.1002/art.42250

Key clinical point: Reduced doses of rituximab can be considered in patients with rheumatoid arthritis (RA) who have had treatment failure with multiple biologic disease-modifying antirheumatic drugs (bDMARD), significant comorbidities, and an initial sustained clinical response.

Major finding: Over a 60-month follow-up, only 7.5% and 5.9% of patients relapsed on low-dose and standard-dose rituximab, respectively (P = .6), with patients on low-dose vs. standard-dose rituximab having significantly lower rates of serious adverse events (incidence rate: 0.77 vs. 1.57 per 1000 person-years; P < .0001) and drug discontinuation due to treatment failure (37.9% vs. 63.6%; P < .0001).

Study details: This was a prospective, observational study including 361 patients with established RA and prior failure using bDMARD who received low-dose (n = 81) or standard-dose (n  =280) rituximab.

Disclosures: The study was partly supported by the Pancretan Health Association. The authors declared no conflicts of interest.

Source: Bertsias A et al. Rheumatoid arthritis patients initiating rituximab with low number of previous bDMARDs failures may effectively reduce rituximab dose and experience fewer serious adverse events than patients on full dose: A 5-year cohort study. Arthritis Res Ther. 2022;24:132 (Jun 2). Doi: 10.1186/s13075-022-02826-6

Key clinical point: Reduced doses of rituximab can be considered in patients with rheumatoid arthritis (RA) who have had treatment failure with multiple biologic disease-modifying antirheumatic drugs (bDMARD), significant comorbidities, and an initial sustained clinical response.

Major finding: Over a 60-month follow-up, only 7.5% and 5.9% of patients relapsed on low-dose and standard-dose rituximab, respectively (P = .6), with patients on low-dose vs. standard-dose rituximab having significantly lower rates of serious adverse events (incidence rate: 0.77 vs. 1.57 per 1000 person-years; P < .0001) and drug discontinuation due to treatment failure (37.9% vs. 63.6%; P < .0001).

Study details: This was a prospective, observational study including 361 patients with established RA and prior failure using bDMARD who received low-dose (n = 81) or standard-dose (n  =280) rituximab.

Disclosures: The study was partly supported by the Pancretan Health Association. The authors declared no conflicts of interest.

Source: Bertsias A et al. Rheumatoid arthritis patients initiating rituximab with low number of previous bDMARDs failures may effectively reduce rituximab dose and experience fewer serious adverse events than patients on full dose: A 5-year cohort study. Arthritis Res Ther. 2022;24:132 (Jun 2). Doi: 10.1186/s13075-022-02826-6

Key clinical point: Reduced doses of rituximab can be considered in patients with rheumatoid arthritis (RA) who have had treatment failure with multiple biologic disease-modifying antirheumatic drugs (bDMARD), significant comorbidities, and an initial sustained clinical response.

Major finding: Over a 60-month follow-up, only 7.5% and 5.9% of patients relapsed on low-dose and standard-dose rituximab, respectively (P = .6), with patients on low-dose vs. standard-dose rituximab having significantly lower rates of serious adverse events (incidence rate: 0.77 vs. 1.57 per 1000 person-years; P < .0001) and drug discontinuation due to treatment failure (37.9% vs. 63.6%; P < .0001).

Study details: This was a prospective, observational study including 361 patients with established RA and prior failure using bDMARD who received low-dose (n = 81) or standard-dose (n  =280) rituximab.

Disclosures: The study was partly supported by the Pancretan Health Association. The authors declared no conflicts of interest.

Source: Bertsias A et al. Rheumatoid arthritis patients initiating rituximab with low number of previous bDMARDs failures may effectively reduce rituximab dose and experience fewer serious adverse events than patients on full dose: A 5-year cohort study. Arthritis Res Ther. 2022;24:132 (Jun 2). Doi: 10.1186/s13075-022-02826-6

Key clinical point: Obefazimod (ABX464) at a dose of 50 mg showed promising efficacy and was safe and well-tolerated in patients with moderate-to-severely active rheumatoid arthritis (RA).

Major finding: A dose of 50 mg ABX464 vs. placebo was associated with numerically more severe adverse events (14.3% vs. 5%) but with no malignancies, opportunistic infections, or deaths, and a significant reduction in the Disease Activity Score 28-C reactive protein (−1.41 vs. −0.60; P = .043) and Clinical Disease Activity Index Score (−15.8 vs. −6.9; P = .020) at week 12.

Study details: This was a phase 2 trial including 60 patients with moderate-to-severely active RA and inadequate response to methotrexate or anti-tumor necrosis factor alpha therapy who were randomly assigned to ABX464 or placebo in combination with methotrexate for 12 weeks.

Disclosures: The study was supported by Abivax. C Daien reported receiving consulting fees, punctual links, or research grants from Abivax and other sources. Ten authors reported being current/former employees or investigators contracted by Abivax.

Source: Daien C et al. Safety and efficacy of the miR-124 upregulator ABX464 (obefazimod, 50 and 100 mg per day) in patients with active rheumatoid arthritis and inadequate response to methotrexate and/or anti-TNFα therapy: A placebo-controlled phase II study. Ann Rheum Dis. 2022 (May 31). Doi: 10.1136/annrheumdis-2022-222228

Key clinical point: Obefazimod (ABX464) at a dose of 50 mg showed promising efficacy and was safe and well-tolerated in patients with moderate-to-severely active rheumatoid arthritis (RA).

Major finding: A dose of 50 mg ABX464 vs. placebo was associated with numerically more severe adverse events (14.3% vs. 5%) but with no malignancies, opportunistic infections, or deaths, and a significant reduction in the Disease Activity Score 28-C reactive protein (−1.41 vs. −0.60; P = .043) and Clinical Disease Activity Index Score (−15.8 vs. −6.9; P = .020) at week 12.

Study details: This was a phase 2 trial including 60 patients with moderate-to-severely active RA and inadequate response to methotrexate or anti-tumor necrosis factor alpha therapy who were randomly assigned to ABX464 or placebo in combination with methotrexate for 12 weeks.

Disclosures: The study was supported by Abivax. C Daien reported receiving consulting fees, punctual links, or research grants from Abivax and other sources. Ten authors reported being current/former employees or investigators contracted by Abivax.

Source: Daien C et al. Safety and efficacy of the miR-124 upregulator ABX464 (obefazimod, 50 and 100 mg per day) in patients with active rheumatoid arthritis and inadequate response to methotrexate and/or anti-TNFα therapy: A placebo-controlled phase II study. Ann Rheum Dis. 2022 (May 31). Doi: 10.1136/annrheumdis-2022-222228

Key clinical point: Obefazimod (ABX464) at a dose of 50 mg showed promising efficacy and was safe and well-tolerated in patients with moderate-to-severely active rheumatoid arthritis (RA).

Major finding: A dose of 50 mg ABX464 vs. placebo was associated with numerically more severe adverse events (14.3% vs. 5%) but with no malignancies, opportunistic infections, or deaths, and a significant reduction in the Disease Activity Score 28-C reactive protein (−1.41 vs. −0.60; P = .043) and Clinical Disease Activity Index Score (−15.8 vs. −6.9; P = .020) at week 12.

Study details: This was a phase 2 trial including 60 patients with moderate-to-severely active RA and inadequate response to methotrexate or anti-tumor necrosis factor alpha therapy who were randomly assigned to ABX464 or placebo in combination with methotrexate for 12 weeks.

Disclosures: The study was supported by Abivax. C Daien reported receiving consulting fees, punctual links, or research grants from Abivax and other sources. Ten authors reported being current/former employees or investigators contracted by Abivax.

Source: Daien C et al. Safety and efficacy of the miR-124 upregulator ABX464 (obefazimod, 50 and 100 mg per day) in patients with active rheumatoid arthritis and inadequate response to methotrexate and/or anti-TNFα therapy: A placebo-controlled phase II study. Ann Rheum Dis. 2022 (May 31). Doi: 10.1136/annrheumdis-2022-222228

Key clinical point: A dose of 5 or 10 mg tofacitinib twice daily improved clinical efficacy outcomes compared with placebo in patients with moderate-to-severe rheumatoid arthritis (RA) regardless of baseline body mass index (BMI).

Major finding: The American College of Rheumatology 20/50/70 response rates at 6 months were significantly higher in patients who received 5 or 10 mg tofacitinib vs. placebo (P < .05) and were comparable across baseline BMI (<25, 25 to <30, and ≥30 kg/m²) categories.

Study details: This was a post hoc analysis of six phase 3 trials including 3880 patients with moderate-to-severe RA who were randomly assigned to receive tofacitinib (5 or 10 mg), placebo, or active controls (methotrexate or adalimumab).

Disclosures: The study was sponsored by Pfizer Inc. Several authors reported being on speaker’s bureaus or receiving grants, consulting fees, or other remuneration from various sources, including Pfizer. Five authors reported being employees or shareholders of Pfizer or companies contracting with Pfizer.

Source: Dikranian AH et al. Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by baseline body mass index: An analysis of pooled data from phase 3 studies. RMD Open. 2022;8:e002103 (May 16). Doi: 10.1136/rmdopen-2021-002103

Key clinical point: A dose of 5 or 10 mg tofacitinib twice daily improved clinical efficacy outcomes compared with placebo in patients with moderate-to-severe rheumatoid arthritis (RA) regardless of baseline body mass index (BMI).

Major finding: The American College of Rheumatology 20/50/70 response rates at 6 months were significantly higher in patients who received 5 or 10 mg tofacitinib vs. placebo (P < .05) and were comparable across baseline BMI (<25, 25 to <30, and ≥30 kg/m²) categories.

Study details: This was a post hoc analysis of six phase 3 trials including 3880 patients with moderate-to-severe RA who were randomly assigned to receive tofacitinib (5 or 10 mg), placebo, or active controls (methotrexate or adalimumab).

Disclosures: The study was sponsored by Pfizer Inc. Several authors reported being on speaker’s bureaus or receiving grants, consulting fees, or other remuneration from various sources, including Pfizer. Five authors reported being employees or shareholders of Pfizer or companies contracting with Pfizer.

Source: Dikranian AH et al. Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by baseline body mass index: An analysis of pooled data from phase 3 studies. RMD Open. 2022;8:e002103 (May 16). Doi: 10.1136/rmdopen-2021-002103

Key clinical point: A dose of 5 or 10 mg tofacitinib twice daily improved clinical efficacy outcomes compared with placebo in patients with moderate-to-severe rheumatoid arthritis (RA) regardless of baseline body mass index (BMI).

Major finding: The American College of Rheumatology 20/50/70 response rates at 6 months were significantly higher in patients who received 5 or 10 mg tofacitinib vs. placebo (P < .05) and were comparable across baseline BMI (<25, 25 to <30, and ≥30 kg/m²) categories.

Study details: This was a post hoc analysis of six phase 3 trials including 3880 patients with moderate-to-severe RA who were randomly assigned to receive tofacitinib (5 or 10 mg), placebo, or active controls (methotrexate or adalimumab).

Disclosures: The study was sponsored by Pfizer Inc. Several authors reported being on speaker’s bureaus or receiving grants, consulting fees, or other remuneration from various sources, including Pfizer. Five authors reported being employees or shareholders of Pfizer or companies contracting with Pfizer.

Source: Dikranian AH et al. Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by baseline body mass index: An analysis of pooled data from phase 3 studies. RMD Open. 2022;8:e002103 (May 16). Doi: 10.1136/rmdopen-2021-002103

As states ban or limit abortion in the wake of the demise of Roe v. Wade, physicians are turning their attention to widely-used drugs that can cause birth defects. At issue: Should these drugs still be prescribed to women of childbearing age if they don’t have the option of terminating their pregnancies?

javi_indy/ Thinkstock

“Doctors are going to understandably be terrified that a patient may become pregnant using a teratogen that they have prescribed,” said University of Pittsburgh rheumatologist Mehret Birru Talabi, MD, PhD, who works in a state where the future of abortion rights is uncertain. “While this was a feared outcome before Roe v. Wade was overturned, abortion provided an escape hatch by which women could avoid having to continue a pregnancy and potentially raise a child with congenital anomalies. I believe that prescribing is going to become much more defensive and conservative. Some clinicians may choose not to prescribe these medications to patients who have childbearing potential, even if they don’t have much risk for pregnancy.”

Other physicians expressed similar concerns in interviews. Duke University, Durham, N.C., rheumatologist Megan E. B. Clowse, MD, MPH, fears that physicians will be wary of prescribing a variety of medications – including new ones for which there are few pregnancy data – if abortion is unavailable. “Women who receive these new or teratogenic medications will likely lose their reproductive autonomy and be forced to choose between having sexual relationships with men, obtaining procedures that make them permanently sterile, or using contraception that may cause intolerable side effects,” she said. “I am very concerned that young women with rheumatic disease will now be left with active disease resulting in joint damage and renal failure.”

Abortion is now banned in at least six states, according to The New York Times. That number may rise to 16 as more restrictions become law. Another five states aren’t expected to ban abortion soon but have implemented gestational age limits on abortion or are expected to adopt them. In another nine states, courts or lawmakers will decide whether abortion remains legal.

Only 20 states and the District of Columbia have firm abortion protections in place.

Numerous drugs are considered teratogens, which means they may cause birth defects. Thalidomide is the most infamous, but there are many more, including several used in rheumatology, dermatology, and gastroenterology. Among the most widely used teratogenic medications are the acne drugs isotretinoin and methotrexate, which are used to treat a variety of conditions, such as cancer, rheumatoid arthritis, and psoriasis.

Dr. Clowse, who helps manage an industry-supported website devoted to reproductive care for women with lupus (www.LupusPregnancy.org), noted that several drugs linked to birth defects and pregnancy loss are commonly prescribed in rheumatology.

“Methotrexate is the most common medication and has been the cornerstone of rheumatoid arthritis [treatment] for at least two decades,” she said. “Mycophenolate is our best medication to treat lupus nephritis, which is inflammation in the kidneys caused by lupus. This is a common complication for young women with lupus, and all of our guideline-recommended treatment regimens include a medication that causes pregnancy loss and birth defects, either mycophenolate or cyclophosphamide.”

Rheumatologists also prescribe a large number of new drugs for which there are few data about pregnancy risks. “It typically takes about two decades to have sufficient data about the safety of our medications,” she said.

Reflecting the sensitivity of the topic, Dr. Clowse made clear that her opinions don’t represent the views of her institution. She works in North Carolina, where the fate of abortion rights is uncertain, according to The New York Times.

What about alternatives? “The short answer is that some of these medications work really well and sometimes much better than the nonteratogenic alternatives,” said Dr. Birru Talabi. “I’m worried about methotrexate. It has been used to induce abortions but is primarily used in the United States as a highly effective treatment for cancer as well as a myriad of rheumatic diseases. If legislators try to restrict access to methotrexate, we may see increasing disability and even death among people who need this medication but cannot access it.”

Rheumatologists aren’t the only physicians who are worrying about the fates of their patients in a new era of abortion restrictions. Gastroenterologist Sunanda Kane, MD, MSPH, of the Mayo Clinic, Rochester, Minn., said several teratogenic medications are used in her field to treat constipation, viral hepatitis, and inflammatory bowel disease.

“When treating women of childbearing age, there are usually alternatives. If we do prescribe a medication with a high teratogenic potential, we counsel and document that we have discussed two forms of birth control to avoid pregnancy. We usually do not prescribe a drug with teratogenic potential with the ‘out’ being an abortion if a pregnancy does occur,” she said. However, “if abortion is not even on the table as an option, we may be much less likely to prescribe these medications. This will be particularly true in patients who clearly do not have the means to travel to have an abortion in any situation.”

Abortion is expected to remain legal in Minnesota, where Dr. Kane practices, but it may be restricted or banned in nearby Wisconsin, depending on the state legislature. None of her patients have had abortions after becoming pregnant while taking the medications, she said, although she “did have a patient who because of her religious faith did not have an abortion after exposure and ended up with a stillbirth.”

The crackdown on abortion won’t just pose risks to patients who take potentially dangerous medications, physicians said. Dr. Kane said pregnancy itself is a significant risk for patients with “very active, uncontrolled gastrointestinal conditions where a pregnancy could be harmful to the mother’s health or result in offspring that are very unhealthy.” These include decompensated cirrhosis, uncontrolled Crohn’s disease or ulcerative colitis, refractory gastroparesis, uncontrolled celiac sprue, and chronic pancreatitis, she said.

“There have been times when after shared decisionmaking, a patient with very active inflammatory bowel disease has decided to terminate the pregnancy because of her own ongoing health issues,” she said. “Not having this option will potentially lead to disastrous results.”

Dr. Clowse, the Duke University rheumatologist, echoed Dr. Kane’s concerns about women who are too sick to bear children. “The removal of abortion rights puts the lives and quality of life for women with rheumatic disease at risk. For patients with lupus and other systemic rheumatic disease, pregnancy can be medically catastrophic, leading to permanent harm and even death to the woman and her offspring. I am worried that women in these conditions will die without lifesaving pregnancy terminations, due to worries about the legal consequences for their physicians.”

The U.S. Supreme Court’s ruling that overturned Roe v. Wade has also raised the prospect that the court could ultimately allow birth control to be restricted or outlawed.

While the ruling states that “nothing in this opinion should be understood to cast doubt on precedents that do not concern abortion,” Justice Clarence Thomas wrote a concurrence in which he said that the court should reconsider a 1960s ruling that forbids the banning of contraceptives. Republicans have dismissed concerns about bans being allowed, although Democrats, including the president and vice president, starkly warn that they could happen.

“If we as providers have to be concerned that there will be an unplanned pregnancy because of the lack of access to contraception,” Dr. Kane said, “this will have significant downstream consequences to the kind of care we can provide and might just drive some providers to not give care to female patients at all given this concern.”

The physicians quoted in this article report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

As states ban or limit abortion in the wake of the demise of Roe v. Wade, physicians are turning their attention to widely-used drugs that can cause birth defects. At issue: Should these drugs still be prescribed to women of childbearing age if they don’t have the option of terminating their pregnancies?

javi_indy/ Thinkstock

“Doctors are going to understandably be terrified that a patient may become pregnant using a teratogen that they have prescribed,” said University of Pittsburgh rheumatologist Mehret Birru Talabi, MD, PhD, who works in a state where the future of abortion rights is uncertain. “While this was a feared outcome before Roe v. Wade was overturned, abortion provided an escape hatch by which women could avoid having to continue a pregnancy and potentially raise a child with congenital anomalies. I believe that prescribing is going to become much more defensive and conservative. Some clinicians may choose not to prescribe these medications to patients who have childbearing potential, even if they don’t have much risk for pregnancy.”

Other physicians expressed similar concerns in interviews. Duke University, Durham, N.C., rheumatologist Megan E. B. Clowse, MD, MPH, fears that physicians will be wary of prescribing a variety of medications – including new ones for which there are few pregnancy data – if abortion is unavailable. “Women who receive these new or teratogenic medications will likely lose their reproductive autonomy and be forced to choose between having sexual relationships with men, obtaining procedures that make them permanently sterile, or using contraception that may cause intolerable side effects,” she said. “I am very concerned that young women with rheumatic disease will now be left with active disease resulting in joint damage and renal failure.”

Abortion is now banned in at least six states, according to The New York Times. That number may rise to 16 as more restrictions become law. Another five states aren’t expected to ban abortion soon but have implemented gestational age limits on abortion or are expected to adopt them. In another nine states, courts or lawmakers will decide whether abortion remains legal.

Only 20 states and the District of Columbia have firm abortion protections in place.

Numerous drugs are considered teratogens, which means they may cause birth defects. Thalidomide is the most infamous, but there are many more, including several used in rheumatology, dermatology, and gastroenterology. Among the most widely used teratogenic medications are the acne drugs isotretinoin and methotrexate, which are used to treat a variety of conditions, such as cancer, rheumatoid arthritis, and psoriasis.

Dr. Clowse, who helps manage an industry-supported website devoted to reproductive care for women with lupus (www.LupusPregnancy.org), noted that several drugs linked to birth defects and pregnancy loss are commonly prescribed in rheumatology.

“Methotrexate is the most common medication and has been the cornerstone of rheumatoid arthritis [treatment] for at least two decades,” she said. “Mycophenolate is our best medication to treat lupus nephritis, which is inflammation in the kidneys caused by lupus. This is a common complication for young women with lupus, and all of our guideline-recommended treatment regimens include a medication that causes pregnancy loss and birth defects, either mycophenolate or cyclophosphamide.”

Rheumatologists also prescribe a large number of new drugs for which there are few data about pregnancy risks. “It typically takes about two decades to have sufficient data about the safety of our medications,” she said.

Reflecting the sensitivity of the topic, Dr. Clowse made clear that her opinions don’t represent the views of her institution. She works in North Carolina, where the fate of abortion rights is uncertain, according to The New York Times.

What about alternatives? “The short answer is that some of these medications work really well and sometimes much better than the nonteratogenic alternatives,” said Dr. Birru Talabi. “I’m worried about methotrexate. It has been used to induce abortions but is primarily used in the United States as a highly effective treatment for cancer as well as a myriad of rheumatic diseases. If legislators try to restrict access to methotrexate, we may see increasing disability and even death among people who need this medication but cannot access it.”

Rheumatologists aren’t the only physicians who are worrying about the fates of their patients in a new era of abortion restrictions. Gastroenterologist Sunanda Kane, MD, MSPH, of the Mayo Clinic, Rochester, Minn., said several teratogenic medications are used in her field to treat constipation, viral hepatitis, and inflammatory bowel disease.

“When treating women of childbearing age, there are usually alternatives. If we do prescribe a medication with a high teratogenic potential, we counsel and document that we have discussed two forms of birth control to avoid pregnancy. We usually do not prescribe a drug with teratogenic potential with the ‘out’ being an abortion if a pregnancy does occur,” she said. However, “if abortion is not even on the table as an option, we may be much less likely to prescribe these medications. This will be particularly true in patients who clearly do not have the means to travel to have an abortion in any situation.”

Abortion is expected to remain legal in Minnesota, where Dr. Kane practices, but it may be restricted or banned in nearby Wisconsin, depending on the state legislature. None of her patients have had abortions after becoming pregnant while taking the medications, she said, although she “did have a patient who because of her religious faith did not have an abortion after exposure and ended up with a stillbirth.”

The crackdown on abortion won’t just pose risks to patients who take potentially dangerous medications, physicians said. Dr. Kane said pregnancy itself is a significant risk for patients with “very active, uncontrolled gastrointestinal conditions where a pregnancy could be harmful to the mother’s health or result in offspring that are very unhealthy.” These include decompensated cirrhosis, uncontrolled Crohn’s disease or ulcerative colitis, refractory gastroparesis, uncontrolled celiac sprue, and chronic pancreatitis, she said.

“There have been times when after shared decisionmaking, a patient with very active inflammatory bowel disease has decided to terminate the pregnancy because of her own ongoing health issues,” she said. “Not having this option will potentially lead to disastrous results.”

Dr. Clowse, the Duke University rheumatologist, echoed Dr. Kane’s concerns about women who are too sick to bear children. “The removal of abortion rights puts the lives and quality of life for women with rheumatic disease at risk. For patients with lupus and other systemic rheumatic disease, pregnancy can be medically catastrophic, leading to permanent harm and even death to the woman and her offspring. I am worried that women in these conditions will die without lifesaving pregnancy terminations, due to worries about the legal consequences for their physicians.”

The U.S. Supreme Court’s ruling that overturned Roe v. Wade has also raised the prospect that the court could ultimately allow birth control to be restricted or outlawed.

While the ruling states that “nothing in this opinion should be understood to cast doubt on precedents that do not concern abortion,” Justice Clarence Thomas wrote a concurrence in which he said that the court should reconsider a 1960s ruling that forbids the banning of contraceptives. Republicans have dismissed concerns about bans being allowed, although Democrats, including the president and vice president, starkly warn that they could happen.

“If we as providers have to be concerned that there will be an unplanned pregnancy because of the lack of access to contraception,” Dr. Kane said, “this will have significant downstream consequences to the kind of care we can provide and might just drive some providers to not give care to female patients at all given this concern.”

The physicians quoted in this article report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

As states ban or limit abortion in the wake of the demise of Roe v. Wade, physicians are turning their attention to widely-used drugs that can cause birth defects. At issue: Should these drugs still be prescribed to women of childbearing age if they don’t have the option of terminating their pregnancies?

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“Doctors are going to understandably be terrified that a patient may become pregnant using a teratogen that they have prescribed,” said University of Pittsburgh rheumatologist Mehret Birru Talabi, MD, PhD, who works in a state where the future of abortion rights is uncertain. “While this was a feared outcome before Roe v. Wade was overturned, abortion provided an escape hatch by which women could avoid having to continue a pregnancy and potentially raise a child with congenital anomalies. I believe that prescribing is going to become much more defensive and conservative. Some clinicians may choose not to prescribe these medications to patients who have childbearing potential, even if they don’t have much risk for pregnancy.”

Other physicians expressed similar concerns in interviews. Duke University, Durham, N.C., rheumatologist Megan E. B. Clowse, MD, MPH, fears that physicians will be wary of prescribing a variety of medications – including new ones for which there are few pregnancy data – if abortion is unavailable. “Women who receive these new or teratogenic medications will likely lose their reproductive autonomy and be forced to choose between having sexual relationships with men, obtaining procedures that make them permanently sterile, or using contraception that may cause intolerable side effects,” she said. “I am very concerned that young women with rheumatic disease will now be left with active disease resulting in joint damage and renal failure.”

Abortion is now banned in at least six states, according to The New York Times. That number may rise to 16 as more restrictions become law. Another five states aren’t expected to ban abortion soon but have implemented gestational age limits on abortion or are expected to adopt them. In another nine states, courts or lawmakers will decide whether abortion remains legal.

Only 20 states and the District of Columbia have firm abortion protections in place.

Numerous drugs are considered teratogens, which means they may cause birth defects. Thalidomide is the most infamous, but there are many more, including several used in rheumatology, dermatology, and gastroenterology. Among the most widely used teratogenic medications are the acne drugs isotretinoin and methotrexate, which are used to treat a variety of conditions, such as cancer, rheumatoid arthritis, and psoriasis.

Dr. Clowse, who helps manage an industry-supported website devoted to reproductive care for women with lupus (www.LupusPregnancy.org), noted that several drugs linked to birth defects and pregnancy loss are commonly prescribed in rheumatology.

“Methotrexate is the most common medication and has been the cornerstone of rheumatoid arthritis [treatment] for at least two decades,” she said. “Mycophenolate is our best medication to treat lupus nephritis, which is inflammation in the kidneys caused by lupus. This is a common complication for young women with lupus, and all of our guideline-recommended treatment regimens include a medication that causes pregnancy loss and birth defects, either mycophenolate or cyclophosphamide.”

Rheumatologists also prescribe a large number of new drugs for which there are few data about pregnancy risks. “It typically takes about two decades to have sufficient data about the safety of our medications,” she said.

Reflecting the sensitivity of the topic, Dr. Clowse made clear that her opinions don’t represent the views of her institution. She works in North Carolina, where the fate of abortion rights is uncertain, according to The New York Times.

What about alternatives? “The short answer is that some of these medications work really well and sometimes much better than the nonteratogenic alternatives,” said Dr. Birru Talabi. “I’m worried about methotrexate. It has been used to induce abortions but is primarily used in the United States as a highly effective treatment for cancer as well as a myriad of rheumatic diseases. If legislators try to restrict access to methotrexate, we may see increasing disability and even death among people who need this medication but cannot access it.”

Rheumatologists aren’t the only physicians who are worrying about the fates of their patients in a new era of abortion restrictions. Gastroenterologist Sunanda Kane, MD, MSPH, of the Mayo Clinic, Rochester, Minn., said several teratogenic medications are used in her field to treat constipation, viral hepatitis, and inflammatory bowel disease.

“When treating women of childbearing age, there are usually alternatives. If we do prescribe a medication with a high teratogenic potential, we counsel and document that we have discussed two forms of birth control to avoid pregnancy. We usually do not prescribe a drug with teratogenic potential with the ‘out’ being an abortion if a pregnancy does occur,” she said. However, “if abortion is not even on the table as an option, we may be much less likely to prescribe these medications. This will be particularly true in patients who clearly do not have the means to travel to have an abortion in any situation.”

Abortion is expected to remain legal in Minnesota, where Dr. Kane practices, but it may be restricted or banned in nearby Wisconsin, depending on the state legislature. None of her patients have had abortions after becoming pregnant while taking the medications, she said, although she “did have a patient who because of her religious faith did not have an abortion after exposure and ended up with a stillbirth.”

The crackdown on abortion won’t just pose risks to patients who take potentially dangerous medications, physicians said. Dr. Kane said pregnancy itself is a significant risk for patients with “very active, uncontrolled gastrointestinal conditions where a pregnancy could be harmful to the mother’s health or result in offspring that are very unhealthy.” These include decompensated cirrhosis, uncontrolled Crohn’s disease or ulcerative colitis, refractory gastroparesis, uncontrolled celiac sprue, and chronic pancreatitis, she said.

“There have been times when after shared decisionmaking, a patient with very active inflammatory bowel disease has decided to terminate the pregnancy because of her own ongoing health issues,” she said. “Not having this option will potentially lead to disastrous results.”

Dr. Clowse, the Duke University rheumatologist, echoed Dr. Kane’s concerns about women who are too sick to bear children. “The removal of abortion rights puts the lives and quality of life for women with rheumatic disease at risk. For patients with lupus and other systemic rheumatic disease, pregnancy can be medically catastrophic, leading to permanent harm and even death to the woman and her offspring. I am worried that women in these conditions will die without lifesaving pregnancy terminations, due to worries about the legal consequences for their physicians.”

The U.S. Supreme Court’s ruling that overturned Roe v. Wade has also raised the prospect that the court could ultimately allow birth control to be restricted or outlawed.

While the ruling states that “nothing in this opinion should be understood to cast doubt on precedents that do not concern abortion,” Justice Clarence Thomas wrote a concurrence in which he said that the court should reconsider a 1960s ruling that forbids the banning of contraceptives. Republicans have dismissed concerns about bans being allowed, although Democrats, including the president and vice president, starkly warn that they could happen.

“If we as providers have to be concerned that there will be an unplanned pregnancy because of the lack of access to contraception,” Dr. Kane said, “this will have significant downstream consequences to the kind of care we can provide and might just drive some providers to not give care to female patients at all given this concern.”

The physicians quoted in this article report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Hydroxychloroquine should be initiated with caution in older patients with rheumatoid arthritis who also have heart failure or are at risk for it, say the authors of a study suggesting that the drug could increase their risk for major adverse cardiovascular events (MACE), compared with methotrexate.

A cohort study published online in the Journal of the American College of Cardiology looked at outcomes in 54,462 patients with RA aged 65 years or older and not previously treated with disease-modifying antirheumatic drugs. Half were initiated on methotrexate and half on hydroxychloroquine, making 27,231 propensity-matched pairs.

Across the entire cohort, hydroxychloroquine was not associated with a higher risk for sudden cardiac arrest, ventricular arrhythmia, or MACE, compared with methotrexate. When broken down into individual cardiovascular events, the data suggested a statistically significant 17% increase in the risk for cardiovascular mortality and 10% increase in all-cause mortality with hydroxychloroquine, although there were no differences in the risks for myocardial infarction or stroke.

However, a subgroup analysis revealed a significant 30% increase in the risk for MACE among patients starting hydroxychloroquine who also had a history of heart failure, compared with patients taking methotrexate. The researchers found no difference between the two drugs in patients without a history of heart failure. The study also suggested an overall 41% increase in the risk for hospitalization with heart failure with hydroxychloroquine, regardless of heart failure history.

Hydroxychloroquine was also associated with a 34% increase in the risk for cardiovascular mortality, a 22% increase in the risk for all-cause mortality, and a 74% increase in the risk for MI.

The lead author of the study, Elvira D’Andrea, MD, PhD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, said that hydroxychloroquine is used as a first-line treatment for RA, but there was limited evidence on its cardiovascular risks. The pandemic in particular shined a spotlight on these concerns and prompted the researchers to extend their original prepandemic study to encompass additional cardiovascular outcomes.

“The emerging concerns on its cardiovascular safety in early 2020 has led the rheumatological community, and patients regularly taking hydroxychloroquine for rheumatoid arthritis, to confusion,” Dr. D’Andrea said in an interview.

She advised that clinicians be cautious when initiating hydroxychloroquine in older patients with existing heart failure or who have risk factors for it. “Although heart failure is a known concern for hydroxychloroquine use, these findings helped to clarify the relationship between the use of hydroxychloroquine or methotrexate and heart failure. Clinicians should pay careful attention to clinical manifestations of cardiomyopathy or heart failure in older patients with rheumatoid arthritis treated with hydroxychloroquine.”

Hydroxychloroquine is associated with cardiotoxicity, particularly cardiomyopathy, which may help precipitate MACE or heart failure exacerbations in patients who already have deterioration of their cardiac tissue, the authors suggested.

Short follow-up period leaves risk attribution under question

In an accompanying editorial, Elizabeth Blair Solow, MD, and Bonnie L. Bermas, MD, of the University of Texas Southwestern Medical Center, Dallas, commented that the lack of an increased risk for arrhythmic events or MACE in the overall cohort taking hydroxychloroquine was reassuring. They also suggested the subgroup analysis findings among patients with preexisting heart failure were still “exploratory and hypothesis-generating” and should be interpreted with caution.

They noted that the follow-up time of the study was relatively short – a median of 209 days – given that hydroxychloroquine does not reach a steady-state level for 6 months.

“Evidence to date suggests cardiomyopathy from HCQ [hydroxychloroquine] takes years to develop, many months beyond the exposures described here, bringing into question as to whether HCQ itself increased HF hospitalizations,” the editorialists wrote.

The editorial also raised the question of whether the association observed in the study was related to a possible cardioprotective effect of methotrexate, given that previous studies have suggested this effect in older patients with RA.

The study authors did an exploratory analysis comparing hydroxychloroquine with sulfasalazine, which appeared to support their main findings of a possible cardiovascular effect of hydroxychloroquine. However, they qualified this by pointing out that the analysis involved small numbers of patients.

Senior investigator Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, also noted that the study only looked at outcomes in patients aged 65 years and older.

“It would be clinically important to further examine the cardiovascular safety of hydroxychloroquine versus methotrexate in a younger population with rheumatic conditions,” she said.

The study was supported by the National Institutes of Health, Brigham and Women’s Hospital, and Harvard Medical School. Four authors declared unrelated research grants from the pharmaceutical sector, with one also declaring stock options and consulting work with the pharmaceutical sector. No other conflicts of interest were declared.

A version of this article first appeared on Medscape.com.

Hydroxychloroquine should be initiated with caution in older patients with rheumatoid arthritis who also have heart failure or are at risk for it, say the authors of a study suggesting that the drug could increase their risk for major adverse cardiovascular events (MACE), compared with methotrexate.

A cohort study published online in the Journal of the American College of Cardiology looked at outcomes in 54,462 patients with RA aged 65 years or older and not previously treated with disease-modifying antirheumatic drugs. Half were initiated on methotrexate and half on hydroxychloroquine, making 27,231 propensity-matched pairs.

Across the entire cohort, hydroxychloroquine was not associated with a higher risk for sudden cardiac arrest, ventricular arrhythmia, or MACE, compared with methotrexate. When broken down into individual cardiovascular events, the data suggested a statistically significant 17% increase in the risk for cardiovascular mortality and 10% increase in all-cause mortality with hydroxychloroquine, although there were no differences in the risks for myocardial infarction or stroke.

However, a subgroup analysis revealed a significant 30% increase in the risk for MACE among patients starting hydroxychloroquine who also had a history of heart failure, compared with patients taking methotrexate. The researchers found no difference between the two drugs in patients without a history of heart failure. The study also suggested an overall 41% increase in the risk for hospitalization with heart failure with hydroxychloroquine, regardless of heart failure history.

Hydroxychloroquine was also associated with a 34% increase in the risk for cardiovascular mortality, a 22% increase in the risk for all-cause mortality, and a 74% increase in the risk for MI.

The lead author of the study, Elvira D’Andrea, MD, PhD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, said that hydroxychloroquine is used as a first-line treatment for RA, but there was limited evidence on its cardiovascular risks. The pandemic in particular shined a spotlight on these concerns and prompted the researchers to extend their original prepandemic study to encompass additional cardiovascular outcomes.

“The emerging concerns on its cardiovascular safety in early 2020 has led the rheumatological community, and patients regularly taking hydroxychloroquine for rheumatoid arthritis, to confusion,” Dr. D’Andrea said in an interview.

She advised that clinicians be cautious when initiating hydroxychloroquine in older patients with existing heart failure or who have risk factors for it. “Although heart failure is a known concern for hydroxychloroquine use, these findings helped to clarify the relationship between the use of hydroxychloroquine or methotrexate and heart failure. Clinicians should pay careful attention to clinical manifestations of cardiomyopathy or heart failure in older patients with rheumatoid arthritis treated with hydroxychloroquine.”

Hydroxychloroquine is associated with cardiotoxicity, particularly cardiomyopathy, which may help precipitate MACE or heart failure exacerbations in patients who already have deterioration of their cardiac tissue, the authors suggested.

Short follow-up period leaves risk attribution under question

In an accompanying editorial, Elizabeth Blair Solow, MD, and Bonnie L. Bermas, MD, of the University of Texas Southwestern Medical Center, Dallas, commented that the lack of an increased risk for arrhythmic events or MACE in the overall cohort taking hydroxychloroquine was reassuring. They also suggested the subgroup analysis findings among patients with preexisting heart failure were still “exploratory and hypothesis-generating” and should be interpreted with caution.

They noted that the follow-up time of the study was relatively short – a median of 209 days – given that hydroxychloroquine does not reach a steady-state level for 6 months.

“Evidence to date suggests cardiomyopathy from HCQ [hydroxychloroquine] takes years to develop, many months beyond the exposures described here, bringing into question as to whether HCQ itself increased HF hospitalizations,” the editorialists wrote.

The editorial also raised the question of whether the association observed in the study was related to a possible cardioprotective effect of methotrexate, given that previous studies have suggested this effect in older patients with RA.

The study authors did an exploratory analysis comparing hydroxychloroquine with sulfasalazine, which appeared to support their main findings of a possible cardiovascular effect of hydroxychloroquine. However, they qualified this by pointing out that the analysis involved small numbers of patients.

Senior investigator Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, also noted that the study only looked at outcomes in patients aged 65 years and older.

“It would be clinically important to further examine the cardiovascular safety of hydroxychloroquine versus methotrexate in a younger population with rheumatic conditions,” she said.

The study was supported by the National Institutes of Health, Brigham and Women’s Hospital, and Harvard Medical School. Four authors declared unrelated research grants from the pharmaceutical sector, with one also declaring stock options and consulting work with the pharmaceutical sector. No other conflicts of interest were declared.

A version of this article first appeared on Medscape.com.

Hydroxychloroquine should be initiated with caution in older patients with rheumatoid arthritis who also have heart failure or are at risk for it, say the authors of a study suggesting that the drug could increase their risk for major adverse cardiovascular events (MACE), compared with methotrexate.

A cohort study published online in the Journal of the American College of Cardiology looked at outcomes in 54,462 patients with RA aged 65 years or older and not previously treated with disease-modifying antirheumatic drugs. Half were initiated on methotrexate and half on hydroxychloroquine, making 27,231 propensity-matched pairs.

Across the entire cohort, hydroxychloroquine was not associated with a higher risk for sudden cardiac arrest, ventricular arrhythmia, or MACE, compared with methotrexate. When broken down into individual cardiovascular events, the data suggested a statistically significant 17% increase in the risk for cardiovascular mortality and 10% increase in all-cause mortality with hydroxychloroquine, although there were no differences in the risks for myocardial infarction or stroke.

However, a subgroup analysis revealed a significant 30% increase in the risk for MACE among patients starting hydroxychloroquine who also had a history of heart failure, compared with patients taking methotrexate. The researchers found no difference between the two drugs in patients without a history of heart failure. The study also suggested an overall 41% increase in the risk for hospitalization with heart failure with hydroxychloroquine, regardless of heart failure history.

Hydroxychloroquine was also associated with a 34% increase in the risk for cardiovascular mortality, a 22% increase in the risk for all-cause mortality, and a 74% increase in the risk for MI.

The lead author of the study, Elvira D’Andrea, MD, PhD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, said that hydroxychloroquine is used as a first-line treatment for RA, but there was limited evidence on its cardiovascular risks. The pandemic in particular shined a spotlight on these concerns and prompted the researchers to extend their original prepandemic study to encompass additional cardiovascular outcomes.

“The emerging concerns on its cardiovascular safety in early 2020 has led the rheumatological community, and patients regularly taking hydroxychloroquine for rheumatoid arthritis, to confusion,” Dr. D’Andrea said in an interview.

She advised that clinicians be cautious when initiating hydroxychloroquine in older patients with existing heart failure or who have risk factors for it. “Although heart failure is a known concern for hydroxychloroquine use, these findings helped to clarify the relationship between the use of hydroxychloroquine or methotrexate and heart failure. Clinicians should pay careful attention to clinical manifestations of cardiomyopathy or heart failure in older patients with rheumatoid arthritis treated with hydroxychloroquine.”

Hydroxychloroquine is associated with cardiotoxicity, particularly cardiomyopathy, which may help precipitate MACE or heart failure exacerbations in patients who already have deterioration of their cardiac tissue, the authors suggested.

Short follow-up period leaves risk attribution under question

In an accompanying editorial, Elizabeth Blair Solow, MD, and Bonnie L. Bermas, MD, of the University of Texas Southwestern Medical Center, Dallas, commented that the lack of an increased risk for arrhythmic events or MACE in the overall cohort taking hydroxychloroquine was reassuring. They also suggested the subgroup analysis findings among patients with preexisting heart failure were still “exploratory and hypothesis-generating” and should be interpreted with caution.

They noted that the follow-up time of the study was relatively short – a median of 209 days – given that hydroxychloroquine does not reach a steady-state level for 6 months.

“Evidence to date suggests cardiomyopathy from HCQ [hydroxychloroquine] takes years to develop, many months beyond the exposures described here, bringing into question as to whether HCQ itself increased HF hospitalizations,” the editorialists wrote.

The editorial also raised the question of whether the association observed in the study was related to a possible cardioprotective effect of methotrexate, given that previous studies have suggested this effect in older patients with RA.

The study authors did an exploratory analysis comparing hydroxychloroquine with sulfasalazine, which appeared to support their main findings of a possible cardiovascular effect of hydroxychloroquine. However, they qualified this by pointing out that the analysis involved small numbers of patients.

Senior investigator Seoyoung C. Kim, MD, ScD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, also noted that the study only looked at outcomes in patients aged 65 years and older.

“It would be clinically important to further examine the cardiovascular safety of hydroxychloroquine versus methotrexate in a younger population with rheumatic conditions,” she said.

The study was supported by the National Institutes of Health, Brigham and Women’s Hospital, and Harvard Medical School. Four authors declared unrelated research grants from the pharmaceutical sector, with one also declaring stock options and consulting work with the pharmaceutical sector. No other conflicts of interest were declared.

A version of this article first appeared on Medscape.com.

The development of depression after a rheumatoid arthritis diagnosis increased the risk for death “more than sixfold” when compared with having no depression at diagnosis, according to Danish researchers.

Cumulative mortality at 10 years was approximately 37% in patients with comorbid RA and depression versus around 13.5% of RA patients with no depression, Jens Kristian Pedersen, MD, PhD, of Odense (Denmark) University Hospital–Svendborg Hospital and the department of clinical research at the University of Southern Denmark, also in Odense, reported at the annual European Congress of Rheumatology.

“According to [antidepressant] exposure status, the cumulative mortality followed two clearly different paths,” Dr. Pedersen said. “The mortality curves separated early and already within the first and second year of follow-up.”
 

RA, depression, and mortality

Rates of depression in patients with RA are high, Dr. Pedersen said, and while it’s previously been reported that their coexistence can increase mortality, this is the first time that the link has been investigated in a population newly diagnosed with RA.

In this study, Dr. Pedersen and collaborators wanted to look at the association in incident RA and defined depression as the first filling of an antidepressant prescription.

“Although antidepressants are used for different indications, we have recently described that in RA the most frequent indication for filling antidepressants is depression,” he explained. Moreover, that research found that “the frequency of filling coincides with the occurrence of depressive disorder previously reported in the scientific literature.”
 

Data sourced from multiple Danish registers

To examine the mortality risk associated with newly diagnosed RA and new-onset depression, Dr. Pedersen described how five different Danish registers were used.

First, data from the DANBIO register were used to identify patients with incident RA living in Denmark over a 10-year period ending in December 2018. Although perhaps widely known as a biologics register, DANBIO is required by the Danish National Board of Health to collect information on all patients with RA, regardless of their treatment.

Next, the Danish National Prescription Register and Danish National Patient Register were consulted to obtain data on patients who had a first prescription for antidepressant treatment and information on those who developed a diagnosis of depression. Demographic, vital status, and socioeconomic data were collated from the Danish Civil Registration System and Statistics Denmark databases.

To be sure they were looking at incident cases of RA and new cases of depression, the researchers excluded anyone with an existing prescription of antidepressants or methotrexate, or who had a confirmed diagnosis of either disorder 3 years prior to the index date of Jan. 1, 2008.

This meant that, from a total population of 18,000 patients in the DANBIO database, there were just over 11,000 who could be included in the analyses.

Overall, the median age at RA diagnosis was 61 years, two-thirds were female, and two-thirds had seropositive disease.

New-onset depression in incident RA

“During follow-up, about 10% filled a prescription of antidepressants,” said Dr. Pedersen, adding that there were 671 deaths, representing around 57,000 person-years at risk.

“The majority died from natural causes,” he said, although the cause of death was unknown in 30% of cases.

Comparing those who did and did not have a prescription for antidepressants, there were some differences in the age at which death occurred, the percentage of females to males, the presence of other comorbidities, and levels of higher education and income. These were all adjusted for in the analyses.

Adjusted hazard rate ratios were calculated to look at the mortality risk in patients who had antidepressant exposure. The highest HRR for mortality with antidepressant use was seen in patients aged 55 years or younger at 6.66, with the next highest HRRs being for male gender (3.70) and seropositive RA (3.45).

But HRRs for seronegative RA, female gender, and age 55-70 years or older than 75 years were all still around 3.0.
 

Depression definition questioned

“My only concern is about the definition of depression in your analysis,” said a member of the audience at the congress.

“You used antidepressant use as a proxy of depression diagnosis, but it might be that most or many patients have taken [medication] like duloxetine for pain control, and you are just seeing higher disease activity and more aggressive RA.”

Dr. Pedersen responded: “After the EULAR 2022 submission deadline, we reanalyzed our data using two other measures of depression.

“First, we use treatment with antidepressants with a positive indication of depression, according to the prescribing physician, and secondly, we used first diagnosis with depression according to ICD-10 Code F32 – ‘depressive episode after discharge from hospital as an outpatient,’ ” he said.

“All definitions end up with a hazard rate ratio of about three. So, in my opinion, it doesn’t matter whether you focus on one measure of depression or the other.”

David Isenberg, MD, FRCP, professor of rheumatology at University College London, wanted to know more about the antecedent history of depression and whether people who had been depressed maybe a decade or 2 decades before, were more likely to get RA.

That calculation has not been done, Dr. Pedersen said, adding that the study also can’t account for people who may have had recurrent depression. Depression treatment guidelines often recommend nonpharmacologic intervention in the first instance, “so we do not necessarily get the right picture of recurrent depression if we look further back.”

Pointing out that the sixfold increase in mortality was impressive, another delegate asked about whether it was because of a higher disease activity or joint damage and if the mortality risk might be lower in patients who are in remission.

“We don’t know that yet,” Dr. Pedersen answered. “We haven’t done the calculations, but there is the issue of residual confounding if we don’t take all relevant covariates into account. So, we need to do that calculation as well.”

The study was supported by the Danish Rheumatism Association. Dr. Pedersen had no conflicts of interest to disclose.
 

The development of depression after a rheumatoid arthritis diagnosis increased the risk for death “more than sixfold” when compared with having no depression at diagnosis, according to Danish researchers.

Cumulative mortality at 10 years was approximately 37% in patients with comorbid RA and depression versus around 13.5% of RA patients with no depression, Jens Kristian Pedersen, MD, PhD, of Odense (Denmark) University Hospital–Svendborg Hospital and the department of clinical research at the University of Southern Denmark, also in Odense, reported at the annual European Congress of Rheumatology.

“According to [antidepressant] exposure status, the cumulative mortality followed two clearly different paths,” Dr. Pedersen said. “The mortality curves separated early and already within the first and second year of follow-up.”
 

RA, depression, and mortality

Rates of depression in patients with RA are high, Dr. Pedersen said, and while it’s previously been reported that their coexistence can increase mortality, this is the first time that the link has been investigated in a population newly diagnosed with RA.

In this study, Dr. Pedersen and collaborators wanted to look at the association in incident RA and defined depression as the first filling of an antidepressant prescription.

“Although antidepressants are used for different indications, we have recently described that in RA the most frequent indication for filling antidepressants is depression,” he explained. Moreover, that research found that “the frequency of filling coincides with the occurrence of depressive disorder previously reported in the scientific literature.”
 

Data sourced from multiple Danish registers

To examine the mortality risk associated with newly diagnosed RA and new-onset depression, Dr. Pedersen described how five different Danish registers were used.

First, data from the DANBIO register were used to identify patients with incident RA living in Denmark over a 10-year period ending in December 2018. Although perhaps widely known as a biologics register, DANBIO is required by the Danish National Board of Health to collect information on all patients with RA, regardless of their treatment.

Next, the Danish National Prescription Register and Danish National Patient Register were consulted to obtain data on patients who had a first prescription for antidepressant treatment and information on those who developed a diagnosis of depression. Demographic, vital status, and socioeconomic data were collated from the Danish Civil Registration System and Statistics Denmark databases.

To be sure they were looking at incident cases of RA and new cases of depression, the researchers excluded anyone with an existing prescription of antidepressants or methotrexate, or who had a confirmed diagnosis of either disorder 3 years prior to the index date of Jan. 1, 2008.

This meant that, from a total population of 18,000 patients in the DANBIO database, there were just over 11,000 who could be included in the analyses.

Overall, the median age at RA diagnosis was 61 years, two-thirds were female, and two-thirds had seropositive disease.

New-onset depression in incident RA

“During follow-up, about 10% filled a prescription of antidepressants,” said Dr. Pedersen, adding that there were 671 deaths, representing around 57,000 person-years at risk.

“The majority died from natural causes,” he said, although the cause of death was unknown in 30% of cases.

Comparing those who did and did not have a prescription for antidepressants, there were some differences in the age at which death occurred, the percentage of females to males, the presence of other comorbidities, and levels of higher education and income. These were all adjusted for in the analyses.

Adjusted hazard rate ratios were calculated to look at the mortality risk in patients who had antidepressant exposure. The highest HRR for mortality with antidepressant use was seen in patients aged 55 years or younger at 6.66, with the next highest HRRs being for male gender (3.70) and seropositive RA (3.45).

But HRRs for seronegative RA, female gender, and age 55-70 years or older than 75 years were all still around 3.0.
 

Depression definition questioned

“My only concern is about the definition of depression in your analysis,” said a member of the audience at the congress.

“You used antidepressant use as a proxy of depression diagnosis, but it might be that most or many patients have taken [medication] like duloxetine for pain control, and you are just seeing higher disease activity and more aggressive RA.”

Dr. Pedersen responded: “After the EULAR 2022 submission deadline, we reanalyzed our data using two other measures of depression.

“First, we use treatment with antidepressants with a positive indication of depression, according to the prescribing physician, and secondly, we used first diagnosis with depression according to ICD-10 Code F32 – ‘depressive episode after discharge from hospital as an outpatient,’ ” he said.

“All definitions end up with a hazard rate ratio of about three. So, in my opinion, it doesn’t matter whether you focus on one measure of depression or the other.”

David Isenberg, MD, FRCP, professor of rheumatology at University College London, wanted to know more about the antecedent history of depression and whether people who had been depressed maybe a decade or 2 decades before, were more likely to get RA.

That calculation has not been done, Dr. Pedersen said, adding that the study also can’t account for people who may have had recurrent depression. Depression treatment guidelines often recommend nonpharmacologic intervention in the first instance, “so we do not necessarily get the right picture of recurrent depression if we look further back.”

Pointing out that the sixfold increase in mortality was impressive, another delegate asked about whether it was because of a higher disease activity or joint damage and if the mortality risk might be lower in patients who are in remission.

“We don’t know that yet,” Dr. Pedersen answered. “We haven’t done the calculations, but there is the issue of residual confounding if we don’t take all relevant covariates into account. So, we need to do that calculation as well.”

The study was supported by the Danish Rheumatism Association. Dr. Pedersen had no conflicts of interest to disclose.
 

The development of depression after a rheumatoid arthritis diagnosis increased the risk for death “more than sixfold” when compared with having no depression at diagnosis, according to Danish researchers.

Cumulative mortality at 10 years was approximately 37% in patients with comorbid RA and depression versus around 13.5% of RA patients with no depression, Jens Kristian Pedersen, MD, PhD, of Odense (Denmark) University Hospital–Svendborg Hospital and the department of clinical research at the University of Southern Denmark, also in Odense, reported at the annual European Congress of Rheumatology.

“According to [antidepressant] exposure status, the cumulative mortality followed two clearly different paths,” Dr. Pedersen said. “The mortality curves separated early and already within the first and second year of follow-up.”
 

RA, depression, and mortality

Rates of depression in patients with RA are high, Dr. Pedersen said, and while it’s previously been reported that their coexistence can increase mortality, this is the first time that the link has been investigated in a population newly diagnosed with RA.

In this study, Dr. Pedersen and collaborators wanted to look at the association in incident RA and defined depression as the first filling of an antidepressant prescription.

“Although antidepressants are used for different indications, we have recently described that in RA the most frequent indication for filling antidepressants is depression,” he explained. Moreover, that research found that “the frequency of filling coincides with the occurrence of depressive disorder previously reported in the scientific literature.”
 

Data sourced from multiple Danish registers

To examine the mortality risk associated with newly diagnosed RA and new-onset depression, Dr. Pedersen described how five different Danish registers were used.

First, data from the DANBIO register were used to identify patients with incident RA living in Denmark over a 10-year period ending in December 2018. Although perhaps widely known as a biologics register, DANBIO is required by the Danish National Board of Health to collect information on all patients with RA, regardless of their treatment.

Next, the Danish National Prescription Register and Danish National Patient Register were consulted to obtain data on patients who had a first prescription for antidepressant treatment and information on those who developed a diagnosis of depression. Demographic, vital status, and socioeconomic data were collated from the Danish Civil Registration System and Statistics Denmark databases.

To be sure they were looking at incident cases of RA and new cases of depression, the researchers excluded anyone with an existing prescription of antidepressants or methotrexate, or who had a confirmed diagnosis of either disorder 3 years prior to the index date of Jan. 1, 2008.

This meant that, from a total population of 18,000 patients in the DANBIO database, there were just over 11,000 who could be included in the analyses.

Overall, the median age at RA diagnosis was 61 years, two-thirds were female, and two-thirds had seropositive disease.

New-onset depression in incident RA

“During follow-up, about 10% filled a prescription of antidepressants,” said Dr. Pedersen, adding that there were 671 deaths, representing around 57,000 person-years at risk.

“The majority died from natural causes,” he said, although the cause of death was unknown in 30% of cases.

Comparing those who did and did not have a prescription for antidepressants, there were some differences in the age at which death occurred, the percentage of females to males, the presence of other comorbidities, and levels of higher education and income. These were all adjusted for in the analyses.

Adjusted hazard rate ratios were calculated to look at the mortality risk in patients who had antidepressant exposure. The highest HRR for mortality with antidepressant use was seen in patients aged 55 years or younger at 6.66, with the next highest HRRs being for male gender (3.70) and seropositive RA (3.45).

But HRRs for seronegative RA, female gender, and age 55-70 years or older than 75 years were all still around 3.0.
 

Depression definition questioned

“My only concern is about the definition of depression in your analysis,” said a member of the audience at the congress.

“You used antidepressant use as a proxy of depression diagnosis, but it might be that most or many patients have taken [medication] like duloxetine for pain control, and you are just seeing higher disease activity and more aggressive RA.”

Dr. Pedersen responded: “After the EULAR 2022 submission deadline, we reanalyzed our data using two other measures of depression.

“First, we use treatment with antidepressants with a positive indication of depression, according to the prescribing physician, and secondly, we used first diagnosis with depression according to ICD-10 Code F32 – ‘depressive episode after discharge from hospital as an outpatient,’ ” he said.

“All definitions end up with a hazard rate ratio of about three. So, in my opinion, it doesn’t matter whether you focus on one measure of depression or the other.”

David Isenberg, MD, FRCP, professor of rheumatology at University College London, wanted to know more about the antecedent history of depression and whether people who had been depressed maybe a decade or 2 decades before, were more likely to get RA.

That calculation has not been done, Dr. Pedersen said, adding that the study also can’t account for people who may have had recurrent depression. Depression treatment guidelines often recommend nonpharmacologic intervention in the first instance, “so we do not necessarily get the right picture of recurrent depression if we look further back.”

Pointing out that the sixfold increase in mortality was impressive, another delegate asked about whether it was because of a higher disease activity or joint damage and if the mortality risk might be lower in patients who are in remission.

“We don’t know that yet,” Dr. Pedersen answered. “We haven’t done the calculations, but there is the issue of residual confounding if we don’t take all relevant covariates into account. So, we need to do that calculation as well.”

The study was supported by the Danish Rheumatism Association. Dr. Pedersen had no conflicts of interest to disclose.
 

CHICAGO – Comorbid autoimmune disease is associated with a greater chance of survival among women with stage IV breast cancer, according to a retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

“It’s counterintuitive that, if you have two diseases instead of one, that you live longer, so then we had to scratch our heads a little bit and think about why these people are living longer,” said lead author Demitrios Dedousis, MD, University Hospitals, Case Medical Center, Cleveland.

Dr. Dedousis and colleagues conducted a retrospective analysis of patients from Surveillance, Epidemiology, and End Results–Medicare databases between 2007 and 2014 with breast cancer. The study included data from 137,324 patients diagnosed between 2007 and 2012, before the widespread use of immunotherapy. 27% of patients had an autoimmune disease, most commonly rheumatoid arthritis (23%), psoriasis (2.4%), and systemic lupus erythematosus (1.1%).

When all patients were included in the analysis, those with autoimmune disorders had slightly longer survival times, but these weren’t clinically significant. A subanalysis found a greater difference in survival.

The association appears more pronounced in metastatic cancer. Patients with stage 4 breast cancer and autoimmune disease had a longer mean overall survival (36 months vs. 30 months; hazard ratio, 1.46; P < .0001. Cancer-specific survival: HR, 1.39; P < .0001). Patients with autoimmune disease and stage 1-3 breast cancer had lower overall survival (P < .0001, P < 0.0001, and P = 0.026 respectively), compared with patients without autoimmune disease.

“What we thought was happening is that the lack of increased survival in stages 1 through 3 was hiding the increase in survival among the stage IV patients when looking at the overall cohort,” Dr. Dedousis said.

The retrospective nature of the study makes it impossible to draw any firm conclusions about causation. It could be that patients who have already been diagnosed with an autoimmune disease are more vigilant about going to health checkups. “There are other possible explanations, but the one that’s most interesting to us is that their immune system is involved in fighting the cancer. Our study certainly didn’t prove that, but it’s suggesting that’s a possibility,” Dr. Dedousis said.

He and his coauthors anticipate conducting similar studies in other cancers to see if there are similar relationships. Some preliminary work has already suggested something similar in lung cancer. “I think demonstrating this in a few kinds of cancer goes part of the way towards showing that this is a real biological phenomenon,” he said.

Another research avenue is to examine the immune systems and pathology specimens in patients with both an autoimmune disease and cancer to see if there is a greater immune response within the tumor. If so, that could suggest new immunotherapy strategies.

Another possibility is to look at the specific immune pathways within “protective” autoimmune conditions. “For the sake of argument, if we find a particular autoimmune condition is improving survival across multiple kinds of cancers, we could look at those pathways that are specifically involved in that autoimmune condition. It might help us identify a target for drug development,” Dr. Dedousis said.

Asked why a potential benefit might be more apparent in late-stage disease, he suggested that, in early-stage breast cancer, surgery and other treatments may be so effective that the immune system’s role only rarely makes a difference. It could play a larger role in late-stage disease when there are less effective therapies. It could also be that the immune system doesn’t recognize the cancer until it has spread beyond the regional lymph nodes on its way to metastasizing.

According to the National Cancer Institute, 10%-30% of people with cancer also have an autoimmune disease.

Dr. Dedousis has no relevant financial disclosures.

CHICAGO – Comorbid autoimmune disease is associated with a greater chance of survival among women with stage IV breast cancer, according to a retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

“It’s counterintuitive that, if you have two diseases instead of one, that you live longer, so then we had to scratch our heads a little bit and think about why these people are living longer,” said lead author Demitrios Dedousis, MD, University Hospitals, Case Medical Center, Cleveland.

Dr. Dedousis and colleagues conducted a retrospective analysis of patients from Surveillance, Epidemiology, and End Results–Medicare databases between 2007 and 2014 with breast cancer. The study included data from 137,324 patients diagnosed between 2007 and 2012, before the widespread use of immunotherapy. 27% of patients had an autoimmune disease, most commonly rheumatoid arthritis (23%), psoriasis (2.4%), and systemic lupus erythematosus (1.1%).

When all patients were included in the analysis, those with autoimmune disorders had slightly longer survival times, but these weren’t clinically significant. A subanalysis found a greater difference in survival.

The association appears more pronounced in metastatic cancer. Patients with stage 4 breast cancer and autoimmune disease had a longer mean overall survival (36 months vs. 30 months; hazard ratio, 1.46; P < .0001. Cancer-specific survival: HR, 1.39; P < .0001). Patients with autoimmune disease and stage 1-3 breast cancer had lower overall survival (P < .0001, P < 0.0001, and P = 0.026 respectively), compared with patients without autoimmune disease.

“What we thought was happening is that the lack of increased survival in stages 1 through 3 was hiding the increase in survival among the stage IV patients when looking at the overall cohort,” Dr. Dedousis said.

The retrospective nature of the study makes it impossible to draw any firm conclusions about causation. It could be that patients who have already been diagnosed with an autoimmune disease are more vigilant about going to health checkups. “There are other possible explanations, but the one that’s most interesting to us is that their immune system is involved in fighting the cancer. Our study certainly didn’t prove that, but it’s suggesting that’s a possibility,” Dr. Dedousis said.

He and his coauthors anticipate conducting similar studies in other cancers to see if there are similar relationships. Some preliminary work has already suggested something similar in lung cancer. “I think demonstrating this in a few kinds of cancer goes part of the way towards showing that this is a real biological phenomenon,” he said.

Another research avenue is to examine the immune systems and pathology specimens in patients with both an autoimmune disease and cancer to see if there is a greater immune response within the tumor. If so, that could suggest new immunotherapy strategies.

Another possibility is to look at the specific immune pathways within “protective” autoimmune conditions. “For the sake of argument, if we find a particular autoimmune condition is improving survival across multiple kinds of cancers, we could look at those pathways that are specifically involved in that autoimmune condition. It might help us identify a target for drug development,” Dr. Dedousis said.

Asked why a potential benefit might be more apparent in late-stage disease, he suggested that, in early-stage breast cancer, surgery and other treatments may be so effective that the immune system’s role only rarely makes a difference. It could play a larger role in late-stage disease when there are less effective therapies. It could also be that the immune system doesn’t recognize the cancer until it has spread beyond the regional lymph nodes on its way to metastasizing.

According to the National Cancer Institute, 10%-30% of people with cancer also have an autoimmune disease.

Dr. Dedousis has no relevant financial disclosures.

CHICAGO – Comorbid autoimmune disease is associated with a greater chance of survival among women with stage IV breast cancer, according to a retrospective study presented at the annual meeting of the American Society of Clinical Oncology.

“It’s counterintuitive that, if you have two diseases instead of one, that you live longer, so then we had to scratch our heads a little bit and think about why these people are living longer,” said lead author Demitrios Dedousis, MD, University Hospitals, Case Medical Center, Cleveland.

Dr. Dedousis and colleagues conducted a retrospective analysis of patients from Surveillance, Epidemiology, and End Results–Medicare databases between 2007 and 2014 with breast cancer. The study included data from 137,324 patients diagnosed between 2007 and 2012, before the widespread use of immunotherapy. 27% of patients had an autoimmune disease, most commonly rheumatoid arthritis (23%), psoriasis (2.4%), and systemic lupus erythematosus (1.1%).

When all patients were included in the analysis, those with autoimmune disorders had slightly longer survival times, but these weren’t clinically significant. A subanalysis found a greater difference in survival.

The association appears more pronounced in metastatic cancer. Patients with stage 4 breast cancer and autoimmune disease had a longer mean overall survival (36 months vs. 30 months; hazard ratio, 1.46; P < .0001. Cancer-specific survival: HR, 1.39; P < .0001). Patients with autoimmune disease and stage 1-3 breast cancer had lower overall survival (P < .0001, P < 0.0001, and P = 0.026 respectively), compared with patients without autoimmune disease.

“What we thought was happening is that the lack of increased survival in stages 1 through 3 was hiding the increase in survival among the stage IV patients when looking at the overall cohort,” Dr. Dedousis said.

The retrospective nature of the study makes it impossible to draw any firm conclusions about causation. It could be that patients who have already been diagnosed with an autoimmune disease are more vigilant about going to health checkups. “There are other possible explanations, but the one that’s most interesting to us is that their immune system is involved in fighting the cancer. Our study certainly didn’t prove that, but it’s suggesting that’s a possibility,” Dr. Dedousis said.

He and his coauthors anticipate conducting similar studies in other cancers to see if there are similar relationships. Some preliminary work has already suggested something similar in lung cancer. “I think demonstrating this in a few kinds of cancer goes part of the way towards showing that this is a real biological phenomenon,” he said.

Another research avenue is to examine the immune systems and pathology specimens in patients with both an autoimmune disease and cancer to see if there is a greater immune response within the tumor. If so, that could suggest new immunotherapy strategies.

Another possibility is to look at the specific immune pathways within “protective” autoimmune conditions. “For the sake of argument, if we find a particular autoimmune condition is improving survival across multiple kinds of cancers, we could look at those pathways that are specifically involved in that autoimmune condition. It might help us identify a target for drug development,” Dr. Dedousis said.

Asked why a potential benefit might be more apparent in late-stage disease, he suggested that, in early-stage breast cancer, surgery and other treatments may be so effective that the immune system’s role only rarely makes a difference. It could play a larger role in late-stage disease when there are less effective therapies. It could also be that the immune system doesn’t recognize the cancer until it has spread beyond the regional lymph nodes on its way to metastasizing.

According to the National Cancer Institute, 10%-30% of people with cancer also have an autoimmune disease.

Dr. Dedousis has no relevant financial disclosures.