Window of Opportunity Remains Elusive in RA

WASHINGTON – Aggressive treatment during the so-called window of opportunity in rheumatoid arthritis can significantly alter disease outcomes.

That was the conclusion of Dr. Vivian Bykerk in a presentation on Tuesday, Nov. 13, at the annual meeting of the American College of Rheumatology.

The window of opportunity is not a new concept, according to Dr. Bykerk, who is with the Inflammatory Arthritis Center at the Hospital for Special Surgery in New York.

Denise Napoli/IMNG Medical Media

"It’s 10 years old," she said, pointing to a 2003 editorial stating that "similar to a primary cancer, early arthritis is less entrenched, has a smaller load of disease cells, and is more responsive to treatment" (Arthritis Rheum. 2003;48:1771-4).

However, it’s unclear exactly what disease state corresponds to this window, said Dr. Bykerk. "Is it during the period of arthralgia or pre-RA? Is it okay to be in a period of early inflammatory arthritis, or can we still win when arthritis is becoming persistent and starting to become destructive, just becoming classifiable?"

One of the most important landmarks in early disease is when "soft tissue damage can begin to occur that is irreversible," she said. "That can start within a year."

Then again, "immune modulator changes occur well before the onset of synovitis," she said, citing a 2004 study showing C-reactive protein levels already elevated in time periods up to 15 years prior to presentation with swollen joints (Arthritis Rheum. 2004;50:2423-7).

At least one study offers compelling evidence for the window being within at least 12 weeks of symptom presentation, said Dr. Bykerk.

Indeed, in a 2010 study, "it’s clear that patients who are treated within 12 weeks of symptom onset have less radiographic damage than patients treated after 12 weeks" (Arthritis Rheum. 2010; 62:3537-46).

And while that study was not a randomized controlled trial, "nonetheless, in the same cohort, patients who are seen earlier have a higher probability of DMARD [disease-modifying antirheumatic drug]-free remission, upwards of 35%, whereas the patients who were seen after 1 year have less than a 12% chance of DMARD-free remission if you follow them out for 7-8 years," she said.

In any case, it is combination therapy that seems to confer the most benefit in this window.

For example, Dr. Bykerk called attention to data showing that in RA of less than 4 months’ duration, treatment with methotrexate plus etanercept was associated with no radiographic progression of disease in 80% of patients after 1 year of treatment (Ann. Rheum. Dis. 2012;71:989-92).

"When combined therapy is used in very early patients, there are significantly more patients who meet these higher criteria outcomes than the patients who [begin treatment later in the course of their RA], but you don’t see that with methotrexate [monotherapy]," she said.

Findings from the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) study also support aggressive, early combination therapy. One group of patients that was randomized to initial methotrexate plus etanercept and another to initial methotrexate plus sulfasalazine plus hydroxychloroquine outperformed patients treated with methotrexate monotherapy at 24 weeks on the DAS28-ESR (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate).

On the other hand, "Does it matter if you miss the window of opportunity? Can patients ‘catch up’ in terms of achieving our high-level goals of remission?" asked Dr. Bykerk.

Indeed, in the TEAR study, initial-monotherapy subjects who switched to a step-up combination therapy arm after the first 24 weeks ultimately had a DAS28-ESR clinical response "that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm" by 102 weeks, according to the authors of that study.

In conclusion, "Future studies need to look at the impact of treatment much, much closer to the onset of disease, so that we can better understand: When does the window open? When does the window close? And what time frame does it truly extend to?" said Dr. Bykerk.

"But is all lost if the window isn’t met? I think not."

Dr. Bykerk disclosed relationships with several pharmaceutical companies, including the makers of biologic and nonbiologic disease-modifying antirheumatic drugs.

WASHINGTON – Aggressive treatment during the so-called window of opportunity in rheumatoid arthritis can significantly alter disease outcomes.

That was the conclusion of Dr. Vivian Bykerk in a presentation on Tuesday, Nov. 13, at the annual meeting of the American College of Rheumatology.

The window of opportunity is not a new concept, according to Dr. Bykerk, who is with the Inflammatory Arthritis Center at the Hospital for Special Surgery in New York.

Denise Napoli/IMNG Medical Media

"It’s 10 years old," she said, pointing to a 2003 editorial stating that "similar to a primary cancer, early arthritis is less entrenched, has a smaller load of disease cells, and is more responsive to treatment" (Arthritis Rheum. 2003;48:1771-4).

However, it’s unclear exactly what disease state corresponds to this window, said Dr. Bykerk. "Is it during the period of arthralgia or pre-RA? Is it okay to be in a period of early inflammatory arthritis, or can we still win when arthritis is becoming persistent and starting to become destructive, just becoming classifiable?"

One of the most important landmarks in early disease is when "soft tissue damage can begin to occur that is irreversible," she said. "That can start within a year."

Then again, "immune modulator changes occur well before the onset of synovitis," she said, citing a 2004 study showing C-reactive protein levels already elevated in time periods up to 15 years prior to presentation with swollen joints (Arthritis Rheum. 2004;50:2423-7).

At least one study offers compelling evidence for the window being within at least 12 weeks of symptom presentation, said Dr. Bykerk.

Indeed, in a 2010 study, "it’s clear that patients who are treated within 12 weeks of symptom onset have less radiographic damage than patients treated after 12 weeks" (Arthritis Rheum. 2010; 62:3537-46).

And while that study was not a randomized controlled trial, "nonetheless, in the same cohort, patients who are seen earlier have a higher probability of DMARD [disease-modifying antirheumatic drug]-free remission, upwards of 35%, whereas the patients who were seen after 1 year have less than a 12% chance of DMARD-free remission if you follow them out for 7-8 years," she said.

In any case, it is combination therapy that seems to confer the most benefit in this window.

For example, Dr. Bykerk called attention to data showing that in RA of less than 4 months’ duration, treatment with methotrexate plus etanercept was associated with no radiographic progression of disease in 80% of patients after 1 year of treatment (Ann. Rheum. Dis. 2012;71:989-92).

"When combined therapy is used in very early patients, there are significantly more patients who meet these higher criteria outcomes than the patients who [begin treatment later in the course of their RA], but you don’t see that with methotrexate [monotherapy]," she said.

Findings from the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) study also support aggressive, early combination therapy. One group of patients that was randomized to initial methotrexate plus etanercept and another to initial methotrexate plus sulfasalazine plus hydroxychloroquine outperformed patients treated with methotrexate monotherapy at 24 weeks on the DAS28-ESR (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate).

On the other hand, "Does it matter if you miss the window of opportunity? Can patients ‘catch up’ in terms of achieving our high-level goals of remission?" asked Dr. Bykerk.

Indeed, in the TEAR study, initial-monotherapy subjects who switched to a step-up combination therapy arm after the first 24 weeks ultimately had a DAS28-ESR clinical response "that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm" by 102 weeks, according to the authors of that study.

In conclusion, "Future studies need to look at the impact of treatment much, much closer to the onset of disease, so that we can better understand: When does the window open? When does the window close? And what time frame does it truly extend to?" said Dr. Bykerk.

"But is all lost if the window isn’t met? I think not."

Dr. Bykerk disclosed relationships with several pharmaceutical companies, including the makers of biologic and nonbiologic disease-modifying antirheumatic drugs.

WASHINGTON – Aggressive treatment during the so-called window of opportunity in rheumatoid arthritis can significantly alter disease outcomes.

That was the conclusion of Dr. Vivian Bykerk in a presentation on Tuesday, Nov. 13, at the annual meeting of the American College of Rheumatology.

The window of opportunity is not a new concept, according to Dr. Bykerk, who is with the Inflammatory Arthritis Center at the Hospital for Special Surgery in New York.

Denise Napoli/IMNG Medical Media

"It’s 10 years old," she said, pointing to a 2003 editorial stating that "similar to a primary cancer, early arthritis is less entrenched, has a smaller load of disease cells, and is more responsive to treatment" (Arthritis Rheum. 2003;48:1771-4).

However, it’s unclear exactly what disease state corresponds to this window, said Dr. Bykerk. "Is it during the period of arthralgia or pre-RA? Is it okay to be in a period of early inflammatory arthritis, or can we still win when arthritis is becoming persistent and starting to become destructive, just becoming classifiable?"

One of the most important landmarks in early disease is when "soft tissue damage can begin to occur that is irreversible," she said. "That can start within a year."

Then again, "immune modulator changes occur well before the onset of synovitis," she said, citing a 2004 study showing C-reactive protein levels already elevated in time periods up to 15 years prior to presentation with swollen joints (Arthritis Rheum. 2004;50:2423-7).

At least one study offers compelling evidence for the window being within at least 12 weeks of symptom presentation, said Dr. Bykerk.

Indeed, in a 2010 study, "it’s clear that patients who are treated within 12 weeks of symptom onset have less radiographic damage than patients treated after 12 weeks" (Arthritis Rheum. 2010; 62:3537-46).

And while that study was not a randomized controlled trial, "nonetheless, in the same cohort, patients who are seen earlier have a higher probability of DMARD [disease-modifying antirheumatic drug]-free remission, upwards of 35%, whereas the patients who were seen after 1 year have less than a 12% chance of DMARD-free remission if you follow them out for 7-8 years," she said.

In any case, it is combination therapy that seems to confer the most benefit in this window.

For example, Dr. Bykerk called attention to data showing that in RA of less than 4 months’ duration, treatment with methotrexate plus etanercept was associated with no radiographic progression of disease in 80% of patients after 1 year of treatment (Ann. Rheum. Dis. 2012;71:989-92).

"When combined therapy is used in very early patients, there are significantly more patients who meet these higher criteria outcomes than the patients who [begin treatment later in the course of their RA], but you don’t see that with methotrexate [monotherapy]," she said.

Findings from the TEAR (Treatment of Early Aggressive Rheumatoid Arthritis) study also support aggressive, early combination therapy. One group of patients that was randomized to initial methotrexate plus etanercept and another to initial methotrexate plus sulfasalazine plus hydroxychloroquine outperformed patients treated with methotrexate monotherapy at 24 weeks on the DAS28-ESR (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate).

On the other hand, "Does it matter if you miss the window of opportunity? Can patients ‘catch up’ in terms of achieving our high-level goals of remission?" asked Dr. Bykerk.

Indeed, in the TEAR study, initial-monotherapy subjects who switched to a step-up combination therapy arm after the first 24 weeks ultimately had a DAS28-ESR clinical response "that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm" by 102 weeks, according to the authors of that study.

In conclusion, "Future studies need to look at the impact of treatment much, much closer to the onset of disease, so that we can better understand: When does the window open? When does the window close? And what time frame does it truly extend to?" said Dr. Bykerk.

"But is all lost if the window isn’t met? I think not."

Dr. Bykerk disclosed relationships with several pharmaceutical companies, including the makers of biologic and nonbiologic disease-modifying antirheumatic drugs.