Real-world use of triple therapy for RA differs from clinical trial use

SAN FRANCISCO – Triple therapy for rheumatoid arthritis has shone in clinical trials, but its adoption by rheumatologists in the trenches of patient care has been lukewarm.

The challenges facing triple therapy were highlighted in two presentations at the annual meeting of the American College of Rheumatology.

In the first, Dr. Jeffrey Sparks noted that findings from several randomized clinical trials have established the noninferiority of triple therapy with methotrexate (MTX), sulfasazine (SUL), and hydroxychloroquine (HCQ), compared with the combination of MTX and tumor necrosis factor inhibitor. Triple therapy also yields comparable quality of life and is delivered at less cost. Reflecting the evidence, triple therapy is an American College of Rheumatology–recommended option for first-line therapy for high disease activity and poor prognosis, and following failure of nonbiologic disease-modifying antirheumatic drugs (DMARDs). “The many options available add to the complexity of RA treatment decisions. It is unclear whether data supporting triple-therapy use have affected prescribing patterns in typical practice in the United States,” said Dr. Sparks of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital, Harvard Medical School, Boston.

Longitudinal data available in the Aetna U.S. insurance claims and Veterans Administration databases allowed a look at the issue. The databases were scrutinized from mid-2009 to mid-2014, and from 2006 through 2012, respectively. The age range was broad – 18 years and older. Of the 24,576 eligible subjects identified in the Aetna insurance claims database, the initial treatment was intensified in 2,920 (11.9%) subjects. Almost all (n = 2,739) involved biologic DMARDs, with only 181 (0.7%) intensifying to triple therapy. The frequency of triple therapy was unrelated to calendar time. Use of triple therapy was not associated with patients’ sex, household income, antimicrobial or opioid use, hospitalization for serious infection, and/or comorbidities.

“Triple therapy was infrequently used for RA treatment in this large nationwide study, reflecting typical clinical practice. Use of steroids and nonsteroidal anti-inflammatory drugs prior to initial nonbiologic DMARD treatment, and geographic location, with more frequent use in the northeastern U.S.A., were associated with triple therapy use,” said Dr. Sparks.

Clinician reluctance to move from the conventional therapy and problems with patient adherence are likely factors in the stalled adoption of triple therapy, Dr. Sparks speculated.

During a separate presentation, Dr. Grant W. Cannon said that the disconnection between randomized controlled trial (RCT) data and the reality of clinical practice also extends to the pattern of drug use in triple therapy. In the VA population, the pattern of introduction of MTX, SUL, and HCQ spanned all possible combinations including the concomitant introduction typical of a RCT. The RCT pattern was infrequent, involving only 20% of the patients. The remaining 80% of cases involved the various patterns of drug introduction, with 57% of patients treated by sequential introduction of the individual DMARDs. No appreciable differences in baseline characteristics were apparent.

Calculation of persistence on therapy revealed that patients were significantly less likely to stay on triple therapy when it was introduced in the RCT style of administering all three DMARDs concomitantly (P less than .01). Adherence to therapy was also worse, although not statistically significantly (P = .096).

“Understanding provider practices with the initiation of triple-drug therapy is important as these practices might impact treatment effectiveness,” said Dr. Cannon of the division of rheumatology, Salt Lake City VA Medical Center and University of Utah, Salt Lake City. “Since clinical response and patient experience during sequential DMARD initiation may affect decisions to progress to triple therapy, RCT results describing the benefits of triple therapy may not generalize to clinical practice.”

SAN FRANCISCO – Triple therapy for rheumatoid arthritis has shone in clinical trials, but its adoption by rheumatologists in the trenches of patient care has been lukewarm.

The challenges facing triple therapy were highlighted in two presentations at the annual meeting of the American College of Rheumatology.

In the first, Dr. Jeffrey Sparks noted that findings from several randomized clinical trials have established the noninferiority of triple therapy with methotrexate (MTX), sulfasazine (SUL), and hydroxychloroquine (HCQ), compared with the combination of MTX and tumor necrosis factor inhibitor. Triple therapy also yields comparable quality of life and is delivered at less cost. Reflecting the evidence, triple therapy is an American College of Rheumatology–recommended option for first-line therapy for high disease activity and poor prognosis, and following failure of nonbiologic disease-modifying antirheumatic drugs (DMARDs). “The many options available add to the complexity of RA treatment decisions. It is unclear whether data supporting triple-therapy use have affected prescribing patterns in typical practice in the United States,” said Dr. Sparks of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital, Harvard Medical School, Boston.

Longitudinal data available in the Aetna U.S. insurance claims and Veterans Administration databases allowed a look at the issue. The databases were scrutinized from mid-2009 to mid-2014, and from 2006 through 2012, respectively. The age range was broad – 18 years and older. Of the 24,576 eligible subjects identified in the Aetna insurance claims database, the initial treatment was intensified in 2,920 (11.9%) subjects. Almost all (n = 2,739) involved biologic DMARDs, with only 181 (0.7%) intensifying to triple therapy. The frequency of triple therapy was unrelated to calendar time. Use of triple therapy was not associated with patients’ sex, household income, antimicrobial or opioid use, hospitalization for serious infection, and/or comorbidities.

“Triple therapy was infrequently used for RA treatment in this large nationwide study, reflecting typical clinical practice. Use of steroids and nonsteroidal anti-inflammatory drugs prior to initial nonbiologic DMARD treatment, and geographic location, with more frequent use in the northeastern U.S.A., were associated with triple therapy use,” said Dr. Sparks.

Clinician reluctance to move from the conventional therapy and problems with patient adherence are likely factors in the stalled adoption of triple therapy, Dr. Sparks speculated.

During a separate presentation, Dr. Grant W. Cannon said that the disconnection between randomized controlled trial (RCT) data and the reality of clinical practice also extends to the pattern of drug use in triple therapy. In the VA population, the pattern of introduction of MTX, SUL, and HCQ spanned all possible combinations including the concomitant introduction typical of a RCT. The RCT pattern was infrequent, involving only 20% of the patients. The remaining 80% of cases involved the various patterns of drug introduction, with 57% of patients treated by sequential introduction of the individual DMARDs. No appreciable differences in baseline characteristics were apparent.

Calculation of persistence on therapy revealed that patients were significantly less likely to stay on triple therapy when it was introduced in the RCT style of administering all three DMARDs concomitantly (P less than .01). Adherence to therapy was also worse, although not statistically significantly (P = .096).

“Understanding provider practices with the initiation of triple-drug therapy is important as these practices might impact treatment effectiveness,” said Dr. Cannon of the division of rheumatology, Salt Lake City VA Medical Center and University of Utah, Salt Lake City. “Since clinical response and patient experience during sequential DMARD initiation may affect decisions to progress to triple therapy, RCT results describing the benefits of triple therapy may not generalize to clinical practice.”

SAN FRANCISCO – Triple therapy for rheumatoid arthritis has shone in clinical trials, but its adoption by rheumatologists in the trenches of patient care has been lukewarm.

The challenges facing triple therapy were highlighted in two presentations at the annual meeting of the American College of Rheumatology.

In the first, Dr. Jeffrey Sparks noted that findings from several randomized clinical trials have established the noninferiority of triple therapy with methotrexate (MTX), sulfasazine (SUL), and hydroxychloroquine (HCQ), compared with the combination of MTX and tumor necrosis factor inhibitor. Triple therapy also yields comparable quality of life and is delivered at less cost. Reflecting the evidence, triple therapy is an American College of Rheumatology–recommended option for first-line therapy for high disease activity and poor prognosis, and following failure of nonbiologic disease-modifying antirheumatic drugs (DMARDs). “The many options available add to the complexity of RA treatment decisions. It is unclear whether data supporting triple-therapy use have affected prescribing patterns in typical practice in the United States,” said Dr. Sparks of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital, Harvard Medical School, Boston.

Longitudinal data available in the Aetna U.S. insurance claims and Veterans Administration databases allowed a look at the issue. The databases were scrutinized from mid-2009 to mid-2014, and from 2006 through 2012, respectively. The age range was broad – 18 years and older. Of the 24,576 eligible subjects identified in the Aetna insurance claims database, the initial treatment was intensified in 2,920 (11.9%) subjects. Almost all (n = 2,739) involved biologic DMARDs, with only 181 (0.7%) intensifying to triple therapy. The frequency of triple therapy was unrelated to calendar time. Use of triple therapy was not associated with patients’ sex, household income, antimicrobial or opioid use, hospitalization for serious infection, and/or comorbidities.

“Triple therapy was infrequently used for RA treatment in this large nationwide study, reflecting typical clinical practice. Use of steroids and nonsteroidal anti-inflammatory drugs prior to initial nonbiologic DMARD treatment, and geographic location, with more frequent use in the northeastern U.S.A., were associated with triple therapy use,” said Dr. Sparks.

Clinician reluctance to move from the conventional therapy and problems with patient adherence are likely factors in the stalled adoption of triple therapy, Dr. Sparks speculated.

During a separate presentation, Dr. Grant W. Cannon said that the disconnection between randomized controlled trial (RCT) data and the reality of clinical practice also extends to the pattern of drug use in triple therapy. In the VA population, the pattern of introduction of MTX, SUL, and HCQ spanned all possible combinations including the concomitant introduction typical of a RCT. The RCT pattern was infrequent, involving only 20% of the patients. The remaining 80% of cases involved the various patterns of drug introduction, with 57% of patients treated by sequential introduction of the individual DMARDs. No appreciable differences in baseline characteristics were apparent.

Calculation of persistence on therapy revealed that patients were significantly less likely to stay on triple therapy when it was introduced in the RCT style of administering all three DMARDs concomitantly (P less than .01). Adherence to therapy was also worse, although not statistically significantly (P = .096).

“Understanding provider practices with the initiation of triple-drug therapy is important as these practices might impact treatment effectiveness,” said Dr. Cannon of the division of rheumatology, Salt Lake City VA Medical Center and University of Utah, Salt Lake City. “Since clinical response and patient experience during sequential DMARD initiation may affect decisions to progress to triple therapy, RCT results describing the benefits of triple therapy may not generalize to clinical practice.”